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When using OncoKB™, please cite: Suehnholz et al., Cancer Discovery 2023 and Chakravarty et al., JCO PO 2017.Updated Therapeutic Implications
Level | Gene | Mutation | Cancer Type | Level-Associated Drug(s) in OncoKB™ | Drug(s) Added to OncoKB™ | Evidence |
---|---|---|---|---|---|---|
1 | ROS1 | Fusions | Non-Small Cell Lung Cancer | Crizotinib, Entrectinib, Repotrectinib (Level 1) | Taletrectinib (Level 1) | FDA approval of taletrectinib; PMID: 40179330 |
1 | ERBB2 | Oncogenic Mutations | Non-Small Cell Lung Cancer | Trastuzumab Deruxtecan (Level 1) | Sevabertinib, Zongertinib (Level 3A) | Abstract: Loong, HH. et al., ASCO 2025; PMID: 40293180 |
Gene | Mutation | Cancer Type | Level-associated Drug(s) in OncoKB™ | Previous Level | Updated Level | Evidence |
---|---|---|---|---|---|---|
KRAS | Oncogenic Mutations | Low-Grade Serous Ovarian Cancer | Drug(s) added to OncoKB™: Avutometinib + Defactinib (Level 1) Drug(s) remaining in OncoKB™: Binimetinib, Cobimetinib, Trametinib (Level 4) | 4 (KRAS G12A/D/R/S/V previously Level 3B) | 1 | FDA approval of avutometinib plus defactinib; Abstract: Grisham et al. Abstract #814605, 2025 SGO Annual Meeting on Women’s Cancer |
Updated Therapeutic Implications
Level | Gene | Mutation | Cancer Type | Drug(s) Added to OncoKB™ | Evidence |
---|---|---|---|---|---|
4 | ERBB2 | Oncogenic Mutations | Biliary Tract Cancer | Neratinib, Trastuzumab Deruxtecan, Pertuzumab + Trastuzumab | PMID: 36746967, 38710187, 38748939 |
Gene | Mutation | Cancer Type | Level-associated Drug(s) in OncoKB™ | Previous Level | Updated Level | Evidence |
---|---|---|---|---|---|---|
ERBB2 | Oncogenic Mutations | Breast Cancer | Drug(s) added to OncoKB™: Neratinib + Trastuzumab + Fulvestrant (Level 2) Drug(s) remaining in OncoKB™: Neratinib (Level 3A) | 3A | 2 | Inclusion in Breast Cancer NCCN Guidelines V3.2025; PMID: 37597578 |
Level | Gene | Mutation | Cancer Type | Level-Associated Drug(s) in OncoKB™ | Drug(s) Added to OncoKB™ | Evidence |
---|---|---|---|---|---|---|
1 | NF1 | Oncogenic Mutations | Neurofibroma | Selumentinib (Level 1) | Mirdametinib (Level 1) | FDA approval of mirdametinib; PMID: 39514826 |
Gene | Mutation | Cancer Type | Level-associated Drug(s) in OncoKB™ | Previous Level | Updated Level | Evidence |
---|---|---|---|---|---|---|
FGFR1 | Fusions | Pancreatic Cancer | Drug(s) promoted in OncoKB™: Erdafitinib (Level 2, previously Level 4) Drug(s) remaining in OncoKB™: Fexagratinib (Level 4) | 4 | 2 | Inclusion in Pancreatic Cancer NCCN Guidelines V2.2025; PMID: 37541273 |
FGFR2 | Fusions | Pancreatic Cancer | Drug(s) promoted in OncoKB™: Erdafitinib (Level 2, previously Level 4) Drug(s) remaining in OncoKB™: Fexagratinib (Level 4) | 4 | 2 | Inclusion in Pancreatic Cancer NCCN Guidelines V2.2025; PMID: 37541273 |
FGFR2 | Oncogenic Mutations | Non-Small Cell Lung Cancer | Drug(s) promoted in OncoKB™: Erdafitinib (Level 2, previously Level 4) Drug(s) remaining in OncoKB™: Fexagratinib, Lirafugratinib (Level 4) | 4 | 2 | Inclusion in Non-Small Cell Lung Cancer NCCN Guidelines V3.2025; PMID: 37541273 |
FGFR3 | Oncogenic Mutations | Non-Small Cell Lung Cancer | Drug(s) promoted in OncoKB™: Erdafitinib (Level 2, previously Level 4) Drug(s) remaining in OncoKB™: Fexagratinib (Level 4) | 4 | 2 | Inclusion in Non-Small Cell Lung Cancer NCCN Guidelines V3.2025; PMID: 37541273 |
Level | Gene | Mutation | Cancer Type | Level-Associated Drug(s) in OncoKB™ | Drug(s) Added to OncoKB™ | Evidence |
---|---|---|---|---|---|---|
1 | BRAF | V600E | Colorectal Cancer | Encorafenib + Cetuximab (Level 1) | Encorafenib + Cetuximab + FOLFOX Regimen (Level 1) | FDA approval of encorafenib with cetuximab and mFOLFOX6; PMID: 39863775 |
Level | Gene | Mutation | Cancer Type | Drug(s) | Evidence |
---|---|---|---|---|---|
2 | ERBB2 | Oncogenic Mutations | Cervical Cancer | Neratinib | Inclusion in Cervical Cancer NCCN Guidelines V1.2025; PMID: 38211393 |
Gene | Mutation | Cancer Type | Level-associated Drug(s) in OncoKB™ | Previous Level | Updated Level | Evidence |
---|---|---|---|---|---|---|
KRAS | G12C | Small Bowel Cancer | Drug(s) promoted in OncoKB™: Adagrasib (Level 2, previously Level 3A) Drug(s) added to OncoKB™: Sotorasib (Level 2) | 3A | 2 | Inclusion in Small Bowel Adenocarcinoma NCCN Guidelines V1.2025; PMID: 32955176, 37099736, 36546659, 34919824 |
Level | Gene | Mutation | Cancer Type | Level-associated Drug(s) in OncoKB™ | Drug(s) updated in OncoKB™ | Evidence |
---|---|---|---|---|---|---|
1 | ALK | Fusions | Non-Small Cell Lung Cancer | Alectinib, Brigatinib, Certinib, Crizotinib, Lorlatinib (Level 1) NVL-655 (Level 3A) | Ensartinib (Level 1) | FDA approval of ensartinib; PMID: 34473194 |
1 | KRAS | G12C | Colorectal Cancer | Sensitivity Adagrasib + Cetuximab (Level 1) Adagrasib + Panitumumab, Sotorasib + Cetuximab, Sotorasib + Panitumumab (Level 2) Binimetinib, Cobimetinib, Trametinib (Level 4) Resistance Cetuximab, Panitumumab, Tucatinib + Trastuzumab (Level R1) | Sotorasib + Panitumumab (Level 1) | FDA approval of sotorasib with panitumumab; PMID: 37870968 |
Gene | Mutation | Cancer Type | Level-associated Drug(s) in OncoKB™ | Previous Level | Updated Level | Evidence |
---|---|---|---|---|---|---|
NRG1 | Fusions | Non-Small Cell Lung Cancer | Drug(s) promoted in OncoKB™: Zenocutuzumab Drug(s) remaining in OncoKB™: Seribantumab (Level 3A) | 3A | 1 | FDA approval of zenocutuzumab; Abstract: Schram, A. et al. Abstract# 1618P, Annals of Oncol. 2023 |
NRG1 | Fusions | Pancreatic Adenocarcinoma | Zenocutuzumab | 3A | 1 | FDA approval of zenocutuzumab; Abstract: Schram, A. et al. Abstract# 1618P, Annals of Oncol. 2023 |
Level | Gene | Mutation | Cancer Type | Level-associated Drug(s) in OncoKB™ | Drug(s) updated in OncoKB™ | Evidence |
---|---|---|---|---|---|---|
2 | ERBB2 | Amplification | Biliary Tract Cancer | Trastuzumab + Pertuzumab, Tucatinib + Trastuzumab (Level 2) | Zanidatamab (Level 3A) | FDA approval of zanidatamab for HER2+ (IHC 3+) biliary tract cancer; PMID: 37276871 |
Level | Gene | Mutation | Cancer Type | Drug(s) | Evidence |
---|---|---|---|---|---|
1 | KMT2A | Fusions | Mixed Phenotype Acute Leukemia | Revumenib | FDA approval of revumenib; PMID: 39121437 |
Gene | Mutation | Cancer Type | Drug(s) remaining in OncoKB™ | Drug(s) added to OncoKB™ | Updated Sensitivity Level | Updated Resistance Level | Evidence |
---|---|---|---|---|---|---|---|
NTRK1 | G595R | All Solid Tumors | Larotrectinib (Level R1), Entrectinib (Level R2) | Selitrectinib (Level 3A) Zurletrectinib (Level 4) | 3A | R1 | PMID: 32133433, 33004339, 28578312, 38902532, 34625502 |
NTRK3 | G623R | All Solid Tumors | Larotrectinib (Level R1) | Selitrectinib (Level 3A) Zurletrectinib (Level 4) | 3A | R1 | PMID: 28578312, 34030125, 37262390, 38902532, 34625502 |
Gene | Mutation | Cancer Type | Level-associated Drug(s) in OncoKB™ | Previous Level | Updated Level | Evidence |
---|---|---|---|---|---|---|
KMT2A | Fusions | Acute Myeloid Leukemia, B-cell Lymphoblastic Leukemia/Lymphoma | Revumenib (Level 3A) | 3A | 1 | FDA approval of revumenib; PMID: 39121437 |
Gene | Mutation | Cancer Type | Current Level of Evidence | Drug(s) removed from OncoKB™ | Drug(s) remaining in OncoKB™ | Evidence |
---|---|---|---|---|---|---|
PIK3CA | H1047R | All Solid Tumors | 4 | LOXO-783, LOXO-783 + Aromatase Inhibition Therapy + Abemaciclib, LOXO-783 + Fulvestrant, LOXO-783 + Fulvestrant + Abemaciclib, LOXO-783 + LY3484356, LOXO-783 + LY3484356 + Abemaciclib, LOXO-783 + Paclitaxel (Level 4) | RLY-2608, RLY-2608 + Fulvestrant (Level 4) | Discontinuation of LOXO-783 development |
Level | Gene | Mutation | Cancer Type | Drug(s) | Evidence |
---|---|---|---|---|---|
3A | ROS1 | G2032R | Non-Small Cell Lung Cancer | Taletrectinib | PMID: 38822758, 31399568 |
R2 | Crizotinib, Lorlatinib | PMID: 33685866, 29333528, 23724914, 36135089, 36135089, 32918045 | |||
3A | ROS1 | L2086F | Non-Small Cell Lung Cancer | Cabozantinib | PMID: 33685866, 37291202, 39117775, 39091594 |
R2 | Lorlatinib, Repotrectinib | PMID: 37291202, 33685866, 39091594 | |||
3A | SMARCA4 | Oncogenic Mutations | Non-Small Cell Lung Cancer, Esophageal Adenocarcinoma | PRT3789 | Abstract: Guo, R. et al., Abstract# 603O, ESMO 2024; Abstract: Hulse, M. et al., Abstract# 3263, AACR 2022 |
Gene | Mutation | Cancer Type | Level-associated Drug(s) in OncoKB™ | Previous Level | Updated Level | Evidence |
---|---|---|---|---|---|---|
PIK3CA | Oncogenic Mutations (excluding R88Q, N345K, C420R, E542K, E545A/D/G/K/Q, Q546E/K/R/P, M1043V/I, H1047Y/R/L, G1049R which are already Level 1) | Breast Cancer | Drug(s) remaining in OncoKB™: Alpelisib + Fulvestrant, Capivasertib + Fulvestrant (Level 2) Inavolisib + Palbociclib + Fulvestrant (Level 3A) Drug(s) promoted in OncoKB™: Inavolisib + Palbociclib + Fulvestrant (Level 1) | 2 | 1 | FDA approval of Inavolisib + Palbociclib + Fulvestrant; Abstract: Jhaveri, K. et al., Abstract# GS03-13, SABCS 2023 |
Level | Gene | Mutation | Cancer Type | Level-associated Drug(s) in OncoKB™ | Drug(s) updated in OncoKB™ | Evidence |
---|---|---|---|---|---|---|
1 | EGFR | Exon 19 in-frame deletions, L858R | Non-Small Cell Lung Cancer | Afatinib, Dacomitinib, Erlotinib, Erlotinib + Ramucirumab, Gefitinib, Osimertinib, Osimertinib + Chemotherapy, Amivantamab + Lazertinib (Level 1) Amivantamab + Chemotherapy (Level 2) Patritumab Deruxtecan (Level 3A) | Amivantamab + Chemotherapy (Level 1) | FDA approval of Amivantamab with Chemotherapy; PMID: 37879444 |
1 | PIK3CA | R88Q, N345K, C420R, E542K, E545A/D/G/K/Q, Q546E/K/R/P, M1043V/I, H1047Y/R/L, G1049R | Breast Cancer | Capivasertib + Fulvestrant (Level 1) Alpelisib + Fulvestrant (Level 1 for PIK3CA C420R, E542K, E545A/D/G/K, H1047Y/R/L, Q546E/R only) | Inavolisib + Palbociclib + Fulvestrant (Level 1; Promoted from Level 3A) | FDA approval of Inavolisib with Palbociclib + Fulvestrant; Abstract: Jhaveri, K. et al., Abstract# GS03-13, SABCS 2023 |
1 | ALK | Fusions | Non-Small Cell Lung Cancer | Alectinib, Brigatinib, Certinib, Crizotinib, Lorlatinib (Level 1) | NVL-655 (Level 3A) | PMID: 39269178; Abstract: Drilon, A. et al., Abstract# 1253O, ESMO 2024 |
1 | ROS1 | Fusions | Non-Small Cell Lung Cancer | Crizotinib, Entrectinib, Repotrectinib (Level 1) Ceritinib, Lorlatinib (Level 2) | Taletrectinib (Level 3A) | PMID: 38822758, 36877099, 31399568 |
2 | ALK | G1202R | Non-Small Cell Lung Cancer | Lorlatinib (Level 2) | NVL-655 (Level 3A) | PMID: 39269178; Abstract: Drilon, A. et al., Abstract# 1253O, ESMO 2024 |
3A | KRAS | G12D | Non-Small Cell Lung Cancer, Pancreatic Adenocarcinoma | RMC-6236 (Level 3A) | ASP3082 (Level 3A; Promoted from Level 4) | Abstract: Park, W. et al., Abstract# 608O, ESMO 2024; Abstract: Nagashima, T. et al., Abstract# 5735, AACR 2023 |
Level | Gene | Mutation | Cancer Type | Drug(s) | Evidence |
---|---|---|---|---|---|
3A | ALK | F1174L/C, F1245Y/V, R1275Q/L | Neuroblastoma | Lorlatinib | PMID: 37012551, 26554404, 38032104, 27483357 |
3A | MET | H1094Y, F1200I | Non-Small Cell Lung Cancer | Elzovantinib | PMID: 38564707 |
4 | MET | N1100S, V1092I, H1106D, R1170Q, M1250T | Non-Small Cell Lung Cancer | Elzovantinib, Capmatinib, Tepotinib | PMID: 38564707 |
Level | Gene | Mutation | Cancer Type | Level-associated Drug(s) in OncoKB™ | Drug(s) updated in OncoKB™ | Evidence |
---|---|---|---|---|---|---|
1 | EGFR | Exon 19 in-frame deletions, L858R | Non-Small Cell Lung Cancer | Afatinib, Dacomitinib, Erlotinib, Erlotinib + Ramucirumab, Gefitinib, Osimertinib, Osimertinib + Chemotherapy (Level 1); Amivantamab + Chemotherapy (Level 2); Amivantamab + Lazertinib, Patritumab Deruxtecan (Level 3A) | Amivantamab + Lazertinib (Level 1; Promoted from Level 3A) | FDA approval of Amivantamab + Lazertinib; PMID: 38924756 |
Level | Gene | Mutation | Cancer Type | Drug(s) | Evidence |
---|---|---|---|---|---|
3A | FBXW7 | Oncogenic Mutations | Endometrial Cancer, Ovarian Cancer | Lunresertib + Camonsertib | PMID: 38410486; Abstract: Yap, T. et al., Abstract# 35396. AACR-NCI-EORTC 2023; Abstract: Gallo, D. et al., Abstract# B057, AACR 2023; Abstract: Yap, T. et al., Abstract# B156, AACR-NCI-EORTC 2023; FDA fast track designation |
3A | PPP2R1A | Oncogenic Mutations | Endometrial Cancer, Ovarian Cancer | Lunresertib + Camonsertib | Abstract: Yap, T. et al., Abstract# 35396. AACR-NCI-EORTC 2023; FDA fast track designation |
4 | FBXW7 | Oncogenic Mutations | All Solid Tumors | Lunresertib + Camonsertib | PMID: 38410486; Abstract: Yap, T. et al., Abstract# 35396. AACR-NCI-EORTC 2023; Abstract: Gallo, D. et al., Abstract# B057, AACR 2023; Abstract: Yap, T. et al., Abstract# B156, AACR-NCI-EORTC 2023 |
4 | PPP2R1A | Oncogenic Mutations | All Solid Tumors | Lunresertib + Camonsertib | Abstract: Yap, T. et al., Abstract# 35396. AACR-NCI-EORTC 2023 |
Gene | Mutation | Cancer Type | Level-associated Drug(s) in OncoKB™ | Previous Level | Updated Level | Evidence |
---|---|---|---|---|---|---|
IDH1 | R132C/H/G/S/L | Oligodendroglioma | Drug(s) remaining in OncoKB™: Ivosidenib (Level 2) Drug(s) added to OncoKB™: Vorasidenib (Level 1) | 2 | 1 | FDA approval of Vorasidenib; PMID: 37272516 |
IDH1 | R132C/H/G/S/L | Astrocytoma | Drug(s) remaining in OncoKB™: Vorasidenib (Level 3A), Ivosidenib (Level 3A) Drug(s) promoted in OncoKB™: Vorasidenib (Level 1), Ivosidenib (Level 2) | 3A | 1 | FDA approval of Vorasidenib; Inclusion of Ivosidenib in NCCN Central Nervous System Guidelines V1.2024; PMID: 32530764, 37272516 |
IDH2 | R172K/M/W/S/G | Astrocytoma, Oligodendroglioma | Vorasidenib | 3A | 1 | FDA approval of Vorasidenib; PMID: 37272516 |
CCNE1 | Amplification | Endometrial Cancer, Ovarian Cancer | Drug(s) remaining in OncoKB™: Lunresertib (Level 4), BLU-222 (Level 4) Drug(s) added to OncoKB™: Lunresertib + Camonsertib (Level 3A) | 4 | 3A | PMID: 38410486; Abstract: Yap, T. et al., Abstract# 35396. AACR-NCI-EORTC 2023; Abstract: Gallo, D. et al., Abstract# B057, AACR 2023; FDA fast track designation |
Gene | Mutation | Cancer Type | Drug(s) | Previous Level | Updated Level | Evidence |
---|---|---|---|---|---|---|
SRSF2, ZRSR2 | Oncogenic Mutations | Acute Myeloid Leukemia | H3B-8800 | 4 | No Level | Discontinuation of H3B-8800 development; Encore-MDS trial failed to meet primary endpoints; PMID: 34172893 |
Gene | Mutation | Cancer Type | Level of Evidence | Level-associated Drug(s) in OncoKB™ | Drug(s) added to OncoKB™ | Evidence |
---|---|---|---|---|---|---|
PIK3CA | R88Q, N345K, C420R, E542K, E545A/D/G/K/Q, Q546E/K/R/P, Q546E/K/R/P, M1043V/I, H1047Y/R/L, G1049R | Breast Cancer | 1 | Capivasertib + Fulvestrant (Level 1); Alpelisib + Fulvestrant (Level 1 for PIK3CA C420R, E542K, E545A/D/G/K, H1047Y/R/L, Q546E/R only) | Inavolisib + Palbociclib + Fulvestrant (Level 3A) | Abstract: Jhaveri, K. et al., Abstract# GS03-13, SABCS 2023; FDA breakthrough therapy designation |
PIK3CA | Oncogenic Mutations (excluding Level 1 mutations listed above) | Breast Cancer | 2 | Alpelisib + Fulvestrant (Level 2); Capivasertib + Fulvestrant (Level 2) | Inavolisib + Palbociclib + Fulvestrant (Level 3A) | Abstract: Jhaveri, K. et al., Abstract# GS03-13, SABCS 2023; FDA breakthrough therapy designation |
CCNE1 | Amplification | All Solid Tumors | 4 | Lunresertib, BLU-222 (Level 4) | Lunresertib + Camonsertib (Level 4) | PMID: 38410486; Abstract: Yap, T. et al., Abstract# 35396. AACR-NCI-EORTC 2023; Abstract: Gallo, D. et al., Abstract# B057, AACR 2023; Abstract: Yap, T. et al., Abstract# B156, AACR-NCI-EORTC 2023 |
SF3B1, U2AF1 | Oncogenic Mutations | Acute Myeloid Leukemia | 4 | H3B-8800 (Level 4; Removed in this update) | Emavusertib (Level 4) | Discontinuation of H3B-8800 development; Encore-MDS trial failed to meet primary endpoints; PMID: 34172893; Abstract: Garcia-Manero, G. et al., Abstract# 7016, JCO, ASCO 2022 |
SF3B1, U2AF1 | Oncogenic Mutations | Myelodysplastic Syndrome | 4 | H3B-8800 (Level 4; Removed in this update) | Emavusertib, Ceralasertib (Level 4) | Discontinuation of H3B-8800 development; Encore-MDS trial failed to meet primary endpoints; PMID: 34172893; Abstract: Garcia-Manero, G. et al., Abstract# 7016, JCO, ASCO 2022; Abstract: Brunner, A. et al., Abstract# P758, HemaSphere, EHA 2022 |
SRSF2, ZRSR2 | Oncogenic Mutations | Myelodysplastic Syndrome | 4 | H3B-8800 (Level 4; Removed in this update) | Ceralasertib (Level 4) | Discontinuation of H3B-8800 development; Encore-MDS trial failed to meet primary endpoints; PMID: 34172893; Abstract: Brunner, A. et al., Abstract# P758, HemaSphere, EHA 2022 |
SF3B1, U2AF1, SRSF2, ZRSR2 | Oncogenic Mutations | Chronic Myelomonocytic Leukemia | 4 | H3B-8800 (Level 4; Removed in this update) | Ceralasertib (Level 4) | Discontinuation of H3B-8800 development; Encore-MDS trial failed to meet primary endpoints; PMID: 34172893; Abstract: Brunner, A. et al., Abstract# P758, HemaSphere, EHA 2022 |
Gene | Mutation | Cancer Type | Level-associated Drug(s) in OncoKB™ | Previous Level | Updated Level | Evidence |
---|---|---|---|---|---|---|
KRAS | G12C | Colorectal Cancer | Drug(s) remaining in OncoKB™: Sensitivity Adagrasib + Cetuximab, Adagrasib + Panitumumab, Sotorasib + Cetuximab, Sotorasib + Panitumumab (Level 2) Resistance Tucatinib + Trastuzumab, Cetuximab, Panitumumab (Level R1) Drug(s) promoted in OncoKB™: Adagrasib + Cetuximab (Level 1) | 2 | 1 | FDA approval of Adagrasib + Cetuximab; PMID: 38587856 |
KRAS | G12C | Biliary Tract Cancer | Adagrasib | 3A | 2 | Inclusion in NCCN Biliary Tract Cancer Guidelines V2.2024; PMID: 37099736 |
Gene | Mutation | Cancer Type | Current Level of Evidence | Drug(s) remaining in OncoKB™ | Drug(s) added to OncoKB™ | Evidence |
---|---|---|---|---|---|---|
EGFR | Exon 19 in-frame deletion, L858R | Non-Small Cell Lung Cancer | 1 | Erlotinib, Afatinib, Gefitinib, Dacomitinib, Erlotinib + Ramucirumab, Osimertinib (Level 1); Patritumab Deruxtecan (Level 3A) | Osimertinib + Chemotherapy (Level 1); Amivantamab + Chemotherapy (Level 2); Amivantamab + Lazertinib (Level 3A) | FDA approval of Osimertinib with Chemotherapy; Inclusion of Amivantamab + Chemotherapy in NCCN Non-Small Cell Lung Cancer Guidelines V5.2024; PMID: 37937763, 37710001, 37879444, 38924756 |
EGFR | S768I, L861Q, G719X | Non-Small Cell Lung Cancer | 1 | Afatinib (Level 1); Osimertinib (Level 2); Patritumab Deruxtecan (Level 3A) | Erlotinib, Gefitinib, Dacomitinib, Amivantamab + Chemotherapy (Level 2); Amivantamab + Lazertinib (Level 3A) | Inclusion of Erlotinib, Gefitinib, Dacomitinib and Amivantamab + Chemotherapy in NCCN Non-Small Cell Lung Cancer Guidelines V5.2024; PMID: 37879444, 25668120, 35770100; Abstract: Cho, B.C. et al., Abstract #8516, ASCO 2024 |
ERBB2 | Amplification | Biliary Tract Cancer | 2 | Trastuzumab + Pertuzumab | Tucatinib + Trastuzumab (Level 2) | Inclusion in NCCN Biliary Tract Cancer Guidelines V2.2024; PMID: 37751561 |
Level | Gene | Mutation | Cancer Type | Drug(s) remaining in OncoKB™ | Drug(s) changed in OncoKB™ | Evidence |
---|---|---|---|---|---|---|
1 | NTRK1, NTRK2, NTRK3 | Fusions | All Solid Tumors | Larotrectinib, Entrectinib (Level 1); Repotrectinib (Level 3A) | Repotrectinib (Level 1) | FDA approval of Repotrectinib; ; Abstract: Solomon, B.J., et al., Abstract #1372P, Ann Oncol Vol 34, Suppl 2, 2023 |
Level | Gene | Mutation | Cancer Type | Drug(s) | Evidence |
---|---|---|---|---|---|
2 | POLE | Exonuclease Domain Missense Mutations (268_471mis) | Colorectal Cancer, Small Bowel Cancer | Pembrolizumab, Nivolumab, Ipilimumab + Nivolumab, Dostarlimab | Inclusion in Colon Cancer NCCN Guidelines V2.2024 and in Small Bowel Adenocarcinoma NCCN Guidelines V3.2024; PMID: 26028255, 31682550, 28734759, 37917058; Abstract: Chae et al. Abstract# 3417, AACR 2020 |
2 | POLD1 | Exonuclease Domain Missense Mutations (304_533mis) | Colorectal Cancer, Small Bowel Cancer | Pembrolizumab, Nivolumab, Ipilimumab + Nivolumab, Dostarlimab | Inclusion in Colon Cancer NCCN Guidelines V2.2024 and in Small Bowel Adenocarcinoma NCCN Guidelines V3.2024; PMID: 26028255, 31682550, 28734759, 37917058; Abstract: Chae et al. Abstract# 3417, AACR 2020 |
3A | MTAP | Deletion | All Solid Tumors | AMG193, MRTX1719 | PMID: 37552839; Abstract: Rodon, J. et al. Abstract# PR006, AACR-NCI-EORTC 2023 |
Gene | Mutation | Cancer Type | Drug(s) remaining in OncoKB™ | Drug(s) added to OncoKB™ | Updated Sensitivity Level | Updated Resistance Level | Evidence |
---|---|---|---|---|---|---|---|
ALK | G1202R | Non-Small Cell Lung Cancer | Alectinib (Level R2) | Lorlatinib (Level 2) | 2 | R2 | Inclusion in the NCCN Non-Small Cell Lung Cancer Guidelines V5.2024; PMID: 30892989 |
ALK | L1196M | Non-Small Cell Lung Cancer | Crizotinib (Level R2) | Lorlatinib (Level 2) | 2 | R2 | Inclusion in the NCCN Non-Small Cell Lung Cancer Guidelines V5.2024; PMID: 30892989 |
Gene | Mutation | Cancer Type | Current Level of Evidence | Drug(s) remaining in OncoKB™ | Drug(s) added to OncoKB™ | Evidence |
---|---|---|---|---|---|---|
Other Biomarkers | MSI-H | Colorectal Cancer | 1 | Pembrolizumab, Nivolumab, Ipilimumab + Nivolumab | Dostarlimab (Level 2) | Inclusion in Colon Cancer NCCN Guidelines V2.2024; PMID: 37917058 |
Other Biomarkers | MSI-H | Small Bowel Cancer | 1 | Pembrolizumab | Nivolumab, Ipilimumab + Nivolumab, Dostarlimab (Level 2) | Inclusion in Small Bowel Adenocarcinoma NCCN Guidelines V3.2024; PMID: 328734759, 37917058; Abstract: Chae et al. Abstract# 3417, AACR 2020 |
ALK | G1202R | Non-Small Cell Lung Cancer | R2 | Alectinib | Crizotinib, Ceritinib, Brigatinib (Level R2) | PMID: 31358542, 29935304, 27432227, 24675041, 25727400, 26698910, 31585938, 22277784 |
Gene | Mutation | Cancer Type | Current Level of Evidence | Drug(s) removed from OncoKB™ | Drug(s) remaining in OncoKB™ | Evidence |
---|---|---|---|---|---|---|
EGFR | Exon 20 in-frame insertions | Non-Small Cell Lung Cancer | 1 | Amivantamab, Amivantamab + Chemotherapy (Level 1); Poziotinib, CLN-081 (Level 3A) | Mobocertinib (Level 1) | Withdrawal of Mobocertinib; EXCLAIM-2 trial failed to meet primary endpoint of PFS; Abstract: Jänne, PA. et al. Abstract# 507O, Annals of Oncol. 2023 |
Gene | Mutation | Cancer Type | Level-associated Drug(s) in OncoKB™ | Previous Level | Updated Level | Evidence |
---|---|---|---|---|---|---|
BRAF | Fusions | Low-Grade Giloma | Tovorafenib | 3B | 1 | FDA approval of Tovorafenib; PMID: 37978284 |
BRAF | V600 (excluding V600E) | Low-Grade Glioma | Tovorafenib | 3B | 1 | FDA approval of Tovorafenib; PMID: 37978284 |
ERBB2 | Amplification | Salivary Gland Cancer | Trastuzumab, Trastuzumab + Docetaxel, Ado-Trastuzumab Emtansine, Trastuzumab Deruxtecan, Trastuzumab + Pertuzumab | 3B | 2 | Inclusion in NCCN Head and Neck Cancer Guidelines V3.2024; PMID: 28006087, 30452336, 31504139, 38231777, 32067683; Abstract: Liu, D. et al. Abstract# 3025, JCO 2023. |
ERBB2 | Amplification | All Solid Tumors (excluding Breast Cancer, Esophagogastric Cancer, and Colorectal Cancer where ERBB2 amplification remains Level 1; Biliary Tract Cancer, Salivary Gland Cancer, and Uterine Cancer where ERBB2 amplification remains Level 2) | Trastuzumab Deruxtecan | 3B | 3A | FDA approval of Trastuzumab Deruxtecan for HER2+ (IHC 3+) Solid Tumors; Clinical response demonstrated in various HER2-expressing (IHC 3+) solid tumors; PMID: 37870536, 38547891, 37286557 |
Gene | Mutation | Cancer Type | Current Level of Evidence | Drug(s) remaining in OncoKB™ | Drug(s) added to OncoKB™ | Evidence |
---|---|---|---|---|---|---|
BRAF | V600E | Low-Grade Glioma | 1 | Dabrafenib + Trametinib (Level 1) | Tovorafenib (Level 1) | FDA approval of Tovorafenib; PMID: 37978284 |
Level(s) | Gene | Mutation | Cancer Type | Drug(s) | Evidence |
---|---|---|---|---|---|
3A | EGFR | L718Q | Non-Small Cell Lung Cancer | Afatinib | PMID: 32146032, 32193290, 31315676 |
R2 | Osimertinib | PMID: 27257132, 29506987, 33937055, 31205925, 34926262, 31315676, 32146032 | |||
R2 | EGFR | L792F | Non-Small Cell Lung Cancer | Osimertinib | PMID: 35932642, 28093244, 29506987, 35422503 |
Gene | Mutation | Cancer Type | Drug(s) remaining in OncoKB™ | Drug(s) added to OncoKB™ | Updated Sensitivity Level | Updated Resistance Level | Evidence |
---|---|---|---|---|---|---|---|
EGFR | G724S | Non-Small Cell Lung Cancer | Osimertinib (Level R2) | Afatinib (Level 3A) | 3A | R2 | PMID: 32093857, 35979997, 33209641, 34590038, 30405134 |
Gene | Mutation | Cancer Type | Level-associated Drug(s) in OncoKB™ | Previous Level | Updated Level | Evidence |
---|---|---|---|---|---|---|
AKT1 | Oncogenic Mutations (excluding E17K, which remains Level 1) | Breast Cancer | Capivasertib + Fulvestrant | 1 | 2 | To adhere to the FDA-drug label and CDx for Capivasertib, Level 1 assignment will be only for AKT1 E17K detected by the FoundationOne CDx test. All other AKT1 oncogenic mutations are Level 2 per their inclusion in the NCCN Breast Cancer Guidelines V2.2024 |
PIK3CA | Oncogenic Mutations (excluding R88Q, N345K, C420R, E542K, E545A, E545D, E545Q, E545K, E545G, Q546E, Q546K, Q546R, Q546P, M1043V, M1043I, H1047Y, H1047R, H1047L and G1049R, which remain Level 1) | Breast Cancer | Drug(s) remaining in OncoKB™: Capivasertib + Fulvestrant (Level 1), Alpelisib + Fulvestrant (Level 2) Drug(s) demoted in OncoKB™: Capivasertib + Fulvestrant (Level 2) | 1 | 2 | To adhere to the FDA-drug label and CDx for Capivasertib, Level 1 assignment will be only for the PIK3CA alterations detected by the FoundationOne CDx test. All other PIK3CA oncogenic mutations are Level 2 per their inclusion in the NCCN Breast Cancer Guidelines V2.2024 |
FGFR1 | Amplification | Lung Squamous Cell Carcinoma | Erdafitinib | 3A | No Level | Limited response rate to EGFR inhibitors for FGFR1-amplified lung squamous cell carcinoma; Discontinuation of infigratinib; PMID: 37909331, 37606995 |
Gene | Mutation | Cancer Type | Level-associated Drug(s) in OncoKB™ | Previous Level | Updated Level | Evidence |
---|---|---|---|---|---|---|
KRAS | G12C | Ampullary Cancer | Sotorasib, Adagrasib | 3B | 2 | Inclusion in NCCN Ampullary Adenocarcinoma Guidelines V1.2024; PMID: 32955176 |
EGFR | L718V | Non-Small Cell Lung Cancer | Drug(s) remaining in OncoKB™: Osimertinib (Level R2), Afatinib (Level 4) Drug(s) promoted in OncoKB™: Afatinib (Level 3A) | 4 | 3A | Ito, T., et al., Current Prob. in cancer, 2023; PMID: 35365043, 31757379, 29571986 |
Gene | Mutation | Cancer Type | Current Level of Evidence | Drug(s) remaining in OncoKB™ | Drug(s) added to OncoKB™ | Evidence |
---|---|---|---|---|---|---|
EGFR | Exon 20 in-frame insertions | Non-Small Cell Lung Cancer | 1 | Amivantamab, Mobocertinib (Level 1); Erlotinib, Afatinib, Gefitinib (Level R1) | Amivantamab + Chemotherapy (Level 1) | FDA approval of Amivantamab + Carboplatin + Pemetrexed; PMID: 37870976 |
Level | Gene | Mutation | Cancer Type | Drug(s) | Evidence |
---|---|---|---|---|---|
3A | MDM2 | Amplification | Intimal Sarcoma | Milademetan | PMID: 37369013 |
Gene | Mutation | Cancer Type | Previous Level | Current Level of Evidence | Drug(s) remaining in OncoKB™ | Drug(s) removed from OncoKB™ | Evidence |
---|---|---|---|---|---|---|---|
FGFR2 | Fusions | Bladder Cancer | Level 1 | No Level | Erdafitinib (Level 1) AZD4547 (Level 4) | Erdafitinib, AZD4547 | Amendment to the FDA-drug label for Erdafitinib; 4/25 (16%) response rate for FGFR2/3 fusion+ bladder cancer, 0/6 (0%) response for FGFR2 fusion+ bladder cancer; PMID: 31340094 |
Gene | Mutation | Cancer Type | Drug(s) | Previous Level | Current Level | Reason |
---|---|---|---|---|---|---|
FGFR3 | Fusions (excluding FGFR3-TACC3 Fusion and FGFR3-BAIAP2L1 Fusion which remain Level 1) | Bladder Cancer | Erdafitinib | 1 | 2 | Adherence to FDA-drug label and CDx for Erdafitinib; Inclusion in NCCN Bladder Cancer Guidelines V3.2023; PMID: 37870920 |
Gene | Mutation | Cancer Type | Drug(s) | Previous Level | Current Level | Reason |
---|---|---|---|---|---|---|
FGFR3 | S371C, G380R, K650 | Bladder Cancer | Erdafitinib | 3A | 2 | Adherence to FDA-drug label and CDx for Erdafitinib; Inclusion in NCCN Bladder Cancer Guidelines V3.2023; PMID: 37870920 |
FGFR3 | Oncogenic Mutations (excluding G370C, R248C, S249C, Y373C which remain Level 1) | 4 | 2 | |||
MDM2 | Amplification | Dedifferentiated Liposarcoma, Well-Differentiated Liposarcoma | Drug(s) remaining in OncoKB™: Milademetan (Level 4) Drug(s) added to OncoKB™: Brigimadlin (Level 3A) | 4 | 3A | PMID: 37269344 |
Gene | Mutation | Cancer Type | Drug(s) | Previous Level | Current Level | Reason |
---|---|---|---|---|---|---|
AKT1 | Oncogenic Mutations | Breast Cancer | Capivasertib + Fulvestrant | 3A (Capivasertib monotherapy for AKT1 E17K only) | 1 | FDA approval of Capivasertib + Fulvestrant; PMID: 37256976 |
PTEN | Oncogenic Mutations | Breast Cancer | Drug(s) remaining in OncoKB™: GSK2636771, AZD8186 (Currently Level 4) Drug(s) added to OncoKB™: Capivasertib + Fulvestrant (Level 1) | 4 | 1 | FDA approval of Capivasertib + Fulvestrant; PMID: 37256976 |
KRAS | G12A/D/R/S/V | Pancreatic Adenocarcinoma, Non-Small Cell Lung Cancer | RMC-6236 | 4 | 3A | Abstract: Arbour, KC. et al. Abstract# 6520, Annals of Oncol. 2023 |
Gene | Mutation | Cancer Type | Current Level of Evidence | Drug(s) remaining in OncoKB™ | Drug(s) added to OncoKB™ | Evidence |
---|---|---|---|---|---|---|
PIK3CA | Oncogenic Mutations | Breast Cancer | 1 | Alpelisib + Fulvestrant (Level 1; select PIK3CA mts only), RLY-2608 + Fulvestrant (Level 4) | Capivasertib + Fulvestrant (Level 1) | FDA approval of Capivasertib + Fulvestrant; PMID: 37256976 |
ROS1 | Fusions | Non-Small Cell Lung Cancer | 1 | Crizotinib, Entrectinib (Level 1), Ceritinib, Lorlatinib (Level 2), Repotrectinib (Level 3A) | Repotrectinib (Promoted to Level 1) | FDA approval of Repotrectinib for ROS1+ NSCLC; Abstract: Cho et al. Abstract# OA03.06, J. of Thoracic Oncol. Nov. 2023 |
Level | Gene | Mutation | Cancer Type | Drug(s) | Evidence |
---|---|---|---|---|---|
3A | EGFR | Amplification | Gastroesophageal Adenocarcinoma | Cetuximab, Cetuximab + Chemotherapy, Panitumumab, Panitumumab + Chemotherapy | PMID: 35349370 |
Gene | Mutation | Cancer Type | Drug(s) | Previous Level | Current Level | Reason |
---|---|---|---|---|---|---|
IDH1 | R132 | Myelodysplastic Syndromes | Ivosidenib | 3B | 1 | FDA approval of Ivosidenib for patients with IDH1-mutant myelodysplastic syndrome; Abstract: DiNardo et al. Abstract# MDS-457, SOHO 2023 |
Gene | Mutation | Cancer Type | Current Level of Evidence | Drug(s) remaining in OncoKB™ | Drug(s) added to OncoKB™ | Evidence |
---|---|---|---|---|---|---|
BRCA1 | Oncogenic Mutations | Prostate Cancer | 1 | Olaparib, Rucaparib, Olaparib + Abiraterone + Prednisone, Talazoparib + Enzalutamide (Level 1) | Niraparib + Abiraterone Acetate + Prednisone (Level 1) | FDA approval of Niraparib + Abiraterone Acetate + Prednisone; PMID: 36952634 |
BRCA2 |
Gene | Mutation | Cancer Type | Drug(s) | Previous Level | Current Level | Reason |
---|---|---|---|---|---|---|
KRAS | G12C | Colorectal Cancer | Drug(s) remaining in OncoKB™: Adagrasib + Cetuximab (Level 3A) Drug(s) added to OncoKB™: Adagrasib + Panitumumab; Sotorasib + Cetuximab; Sotorasib + Panitumumab | 3A | 2 | Inclusion in Colon Cancer NCCN guidelines v3.2023 and in Rectal Cancer NCCN guidelines v5.2023; PMID: 36546659; Abstract: Kuboki et al. Abstract# 45MO, ESMO 2022. |
Gene | Mutation | Cancer Type | Current Level of Evidence | Drug(s) remaining in OncoKB™ | Drug(s) added to OncoKB™ | Evidence |
---|---|---|---|---|---|---|
BRAF | V600E | Non-Small Cell Lung Cancer | 1 | Dabrafenib + Trametinib (Level 1) | Encorafenib + Binimetinib (Level 1) | FDA approval of Encorafenib + Binimetinib for BRAF V600E NSCLC; PMID: 37270692 |
Gene | Mutation | Cancer Type | Drug(s) | Previous Level | Current Level | Reason |
---|---|---|---|---|---|---|
RET | Oncogenic Mutations | Medullary Thyroid Cancer (MTC) | Pralsetinib | 1 | 3A | Withdrawal of FDA approval for Pralsetinib for RET-mutant MTC |
ALK | Oncogenic Mutations | Non-Small Cell Lung Cancer | Lorlatinib | 1 | No level | Adherence to FDA drug label and CDx for Lorlatinib |
Gene | Mutation | Cancer Type | Current Level of Evidence | Drug(s) remaining in OncoKB™ | Drug(s) added to OncoKB™ | Evidence |
---|---|---|---|---|---|---|
Other Biomarkers | MSI-H | Endometrial Cancer | 1 | Pembrolizumab (All Solid Tumors) | Dostarlimab + Carboplatin + Paclitaxel (Level 1, Endometrial Cancer) | FDA approval of Dostarlimab for MSI-H endometrial cancer; PMID: 36972026 |
Gene | Mutation | Cancer Type | Current Level of Evidence | Drug(s) remaining in OncoKB™ | Drug(s) added to OncoKB™ | Evidence |
---|---|---|---|---|---|---|
FLT3 | Internal Tandem Duplications (ITD) | Acute Myeloid Leukemia | 1 | Gilteritinib (Level 1), Midostaurin + High Dose Chemotherapy (Level 1), Crenolanib (Level 3A), Quizartinib (Level 3A) | Quizartinib (Promoted to Level 1) | FDA approval of Quizartinib; PMID: 37116523 |
Gene | Mutation | Cancer Type | Drug(s) | Previous Level | Current Level | Reason |
---|---|---|---|---|---|---|
FGFR2 | Oncogenic Mutations | Cholangiocarcinoma | RLY-4008 (Level 3A); Erdafitinib and AZD4547 (Currently Level 4) | 4 | 3A | Abstract: Borad et al. Abstract# 4009, ASCO 2023 |
IDH1 | R132 | Oligodendroglioma | Ivosidenib | 3A | 2 | Inclusion in CNS NCCN Guidelines v1.2023; PMID: 32530764 |
Level | Gene | Mutation | Cancer Type | Drug(s) | Evidence |
---|---|---|---|---|---|
1 | ATR | Oncogenic Mutations | Prostate Cancer | Talazoparib + Enzalutamide | FDA approval of Talazoparib + Enzalutamide; PMID: 37285865 |
1 | FANCA | ||||
1 | MLH1 | ||||
1 | MRE11 | ||||
1 | NBN | ||||
2 | IDH1 | Oncogenic Mutations | Oligodendroglioma | Ivosidenib | Inclusion in CNS NCCN Guidelines v1.2023; PMID: 32530764 |
3A | IDH2 | R172 | Oligodendroglioma, Astrocytoma | Vorasidenib | PMID: 37272516 |
4 | KRAS | G12 | All Solid Tumors | RMC-6236 | Abstract: Koltun et al. Abstract# 3597, AACR 2022 |
4 | FGFR2 | Amplification | All Solid Tumors | RLY-4008 | Abstract: Borad et al. Abstract# 4009, ASCO 2023 |
Gene | Mutation | Cancer Type | Current Level of Evidence | Drug(s) currently in OncoKB | Drug(s) added to OncoKB | Evidence |
---|---|---|---|---|---|---|
ALK | Fusions | Inflammatory Myofibroblastic Tumors | 1 | Crizotinib (Level 1); Brigatinib, Lorlatinib, Ceritinib (Level 2) | Alectinib (Level 2) | Inclusion in Soft Tissue Sarcoma NCCN Guidelines v2.2023 |
FGFR2 | Fusions | Cholangiocarcinoma | 1 | Futibatinib, Pemigatinib (Level 1) | RLY-4008 (Level 3A) | Abstract: Borad et al. Abstract# 4009, ASCO 2023 |
BRCA1 | Oncogenic Mutations | Prostate Cancer | 1 | Olaparib, Rucaparib (Level 1) | Talazoparib + Enzalutamide (Level 1) | FDA approval of Talazoparib + Enzalutamide; PMID: 37285865 |
Olaparib + Abiraterone + Prednisone/Prednisolone (Level 1) | FDA approval of Olaparib + Abiraterone + Prednisone/Prednisolone; Abstract: Clarke et al. Abstract# LBA16, ASCO GUCS 2023 | |||||
BRCA2 | Oncogenic Mutations | Prostate Cancer | 1 | Olaparib, Rucaparib (Level 1) | Talazoparib + Enzalutamide (Level 1) | FDA approval of Talazoparib + Enzalutamide; PMID: 37285865 |
Olaparib + Abiraterone + Prednisone/Prednisolone (Level 1) | FDA approval of Olaparib + Abiraterone + Prednisone/Prednisolone; Abstract: Clarke et al. Abstract# LBA16, ASCO GUCS 2023 | |||||
ATM | Oncogenic Mutations | Prostate Cancer | 1 | Olaparib (Level 1) | Talazoparib + Enzalutamide (Level 1) | FDA approval of Talazoparib + Enzalutamide; PMID: 37285865 |
PALB2 | ||||||
CDK12 | ||||||
CHEK2 | ||||||
RAD51C | ||||||
IDH1 | R132 | Oligodendroglioma, Astrocytoma | 3A | Ivosidenib | Vorasidenib (Level 3A) | PMID: 37272516 |
FGFR2 | Oncogenic Mutations | All Solid Tumors | 4 | Erdafitinib and AZD4547 (Level 4) | RLY-4008 (Level 4) | Abstract: Borad et al. Abstract# 4009, ASCO 2023 |
KRAS | G12D | All Solid Tumors | 4 | RMC-6236 | MRTX-1133 and ASP3082 (level 4) | Abstract: Nagashima et al. Abstract# 5735, AACR 2023; PMID: 36472553 |
Gene | Mutation | Cancer Type | Current Level of Evidence | Drug(s) currently in OncoKB | Drug(s) removed from OncoKB | Evidence |
---|---|---|---|---|---|---|
FGFR1 | Amplification | Lung Squamous Cell Carcinoma | 3A | Erdafitinib | Debio1347 | Failed in basket study - no further clinical development |
FGFR1, FGFR2, FGFR3 | Oncogenic Mutations | All Solid Tumors | 4 | Erdafitinib, AZD4547 |
Level | Gene | Mutation | Cancer Type | Drug(s) | Evidence |
---|---|---|---|---|---|
1 | RARA | PML-RARA Fusion | Acute Promyelocytic Leukemia | Tretinoin | PMID: 1850498; FDA approval (1995) of Tretinoin |
Arsenic Trioxide | PMID: 11559723; FDA approval (2000) of Arsenic Trioxide | ||||
Tretinoin + Arsenic Trioxide | PMID: 23841729; FDA approval (2000) of Arsenic Trioxide + Tretinoin | ||||
2 | ERBB2 | Amplification | Biliary Tract Cancer | Trastuzumab + Pertuzumab | Inclusion in Biliary Tract Cancer NCCN guidelines (v2.2023) |
R2 | EGFR | L792H | Non-Small Cell Lung Cancer | Osimertinib | PMID: 28093244, 28625641, 29506987, 29857056, 34526717 |
Gene | Mutation | Cancer Type | Drug(s) | Previous Level | Current Level | Reason |
---|---|---|---|---|---|---|
ESR1 | Oncogenic ligand-binding domain in-frame insertions or deletions | Breast Cancer | Elacestrant | 3A | 2 | Inclusion in Breast Cancer NCCN guidelines (v4.2023) |
KRAS | G12C | Pancreatic Adenocarcinoma | Adagrasib, Sotorasib | 3A | 2 | Inclusion in Pancreatic Cancer NCCN guidelines (v1.2023) |
Gene | Mutation | Cancer Type | Current Level of Evidence | Drug(s) removed from OncoKB | Drug(s) remaining in OncoKB | Evidence |
---|---|---|---|---|---|---|
FGFR2 | Fusions | Cholangiocarcinoma | 1 | Infigratinib | Pemigatinib, Futibatinib | Discontinuation of infigratinib |
FGFR1 | Amplification | Lung Squamous Cell Carcinoma | 3A | Debio1347, Erdafitinib | ||
FGFR1, FGFR2, FGFR3 | Oncogenic Mutations | All Solid Tumors | 4 | Debio1347, Erdafitinib, AZD4547 |
Gene | Mutation | Cancer Type | Previous Level of Evidence | Current Level of Evidence | Drug(s) remaining in OncoKB™ | Drug(s) added to OncoKB™ | Evidence |
---|---|---|---|---|---|---|---|
ESR1 | Oncogenic Ligand-Binding Domain Missense Mutations (310_547) | Breast Cancer | 3A | 1 | Fulvestrant (Level 3A) | Elacestrant (Level 1) | FDA approval of elacestrant in breast cancer |
ESR1 | Oncogenic Ligand-Binding Domain In-Frame Insertions or Deletions (310_547) | Breast Cancer | 3A | 3A | Fulvestrant (Level 3A) | Elacestrant (Level 3A) | FDA approval of elacestrant in breast cancer (Level 1 ESR1 mutations limited to those specified in corresponding FDA-approved CDx) |
Gene | Mutation | Cancer Type | Drug(s) | Previous Level | Current Level | Evidence |
---|---|---|---|---|---|---|
ERBB2 | Amplification | Colorectal Cancer | Tucatinib + Trastuzumab | 2 | 1 | FDA approval of tucatinib + trastuzumab in colorectal cancer |
Gene | Mutation | Cancer Type | Current Level of Evidence | Drug(s) remaining in OncoKB™ | Drug(s) added to OncoKB™ | Evidence |
---|---|---|---|---|---|---|
KRAS, NRAS | Oncogenic Mutations | Colorectal Cancer | R1 | Cetuximab, Panitumumab | Tucatinib + Trastuzumab | FDA approval of tucatinib + trastuzumab in colorectal cancer |
Gene | Mutation | Cancer Type | Current Level of Evidence | Drug(s) remaining in OncoKB™ | Drug(s) added to OncoKB™ | Evidence |
---|---|---|---|---|---|---|
KRAS | G12C | Non-Small Cell Lung Cancer | 1 | Sotorasib | Adagrasib (Level 1) | FDA approval of adagrasib in NSCLC; Abstract: Spira et al. Abstract# 9002, ASCO 2022 |
Gene | Mutation | Cancer Type | Current Level of Evidence | Drug(s) remaining in OncoKB™ | Drug(s) added to OncoKB™ | Evidence |
---|---|---|---|---|---|---|
IDH1 | R132C/H/L/G/S | Acute Myeloid Leukemia | 1 | Ivosidenib | Olutasidenib (Level 1) | FDA approval of olutasidenib in AML; Abstract: Cortes et al. Abstract #6193, ASH 2022 |
Level | Gene | Mutation | Cancer Type | Drug(s) | Evidence |
---|---|---|---|---|---|
1 | RET | Fusions | All Solid Tumors | Selpercatinib | FDA approval of selpercatinib in solid tumors; Abstract: Subbiah et al. Abstract# 3094, ASCO 2022 |
3A | TP53 | Y220C | All Solid Tumors | PC14586 | Abstract: Dumbrava et al. Abstract# 3003, ASCO 2022; Abstract: Dumble et al. Abstract# LB006, AACR 2021 |
4 | PIK3CA | Oncogenic Mutations | All Solid Tumors | RLY-2608 | Abstract: Perez et al. Abstract# TPS1124, ASCO 2022 |
4 | PIK3CA | H1047R | All Solid Tumors (excluding Colorectal Cancer) | LOXO-783 | Abstract: Klippel et al. Abstract# P142, AACR-NCI-EORTC 2021 |
4 | CCNE1 | Amplification | All Solid Tumors | RP-6306, BLU-222 | Abstract: Brown et al. Abstract# 2306, AACR 2022; PMID: 35444283 |
4 | KRAS | G12D | All Solid Tumors | RMC-6236 | Abstract: Koltun et al. Abstract# 3597, AACR 2022 |
Gene | Mutation | Cancer Type | Current Level of Evidence | Drug(s) remaining in OncoKB™ | Drug(s) added to OncoKB™ | Evidence |
---|---|---|---|---|---|---|
FGFR2 | Fusions | Cholangiocarcinoma | 1 | Infigratinib, Pemigatinib | Futibatinib (Level 1) | FDA approval of futibatinib in cholangiocarcinoma; Abstract: Goyal et al. Abstract# 4009, ASCO 2022 |
MET | Amplification | Non-Small Cell Lung Cancer | 2 | Crizotinib, Capmatinib, Tepotinib | Telisotuzumab Vedotin (Level 3A) | Abstract: Camidge et al. Abstract# 9016, ASCO 2022 |
PIK3CA | C420R, E542K, E545A, E545D, E545G, E545K, Q546E, Q546R, H1047L, H1047R, H1047Y | Breast Cancer | 1 | Alpelisib + Fulvestrant | RLY-2608 + Fulvestrant (Level 4) | Abstract: Perez et al. Abstract# TPS1124, ASCO 2022 |
PIK3CA | Oncogenic Mutations (excluding C420R, E542K, E545A, E545D, E545G, E545K, Q546E, Q546R, H1047L, H1047R, and H1047Y) | Breast Cancer | 2 | Alpelisib + Fulvestrant | RLY-2608 + Fulvestrant (Level 4) | Abstract: Perez et al. Abstract# TPS1124, ASCO 2022 |
PIK3CA | H1047R | Breast Cancer | 1 | Alpelisib + Fulvestrant | LOXO-783 + Fulvestrant +/- Abemaciclib, LOXO-783 + LY3484356 +/- Abemaciclib, LOXO-783 + Aromitase Inhibitors + Abemaciclib, LOXO-783 + Nab-Paclitaxel (Level 4) | Abstract: Klippel et al. Abstract# P142, AACR-NCI-EORTC 2021 |
Level | Gene | Mutation | Cancer Type | Drug(s) | Evidence |
---|---|---|---|---|---|
1 | BRAF | V600E | All Solid Tumors (excluding Colorectal Cancer) | Dabrafenib + Trametinib | FDA approval of dabrafenib + trametinib in solid tumors |
Gene | Mutation | Cancer Type | Drug(s) | Previous Level | Current Level | Reason |
---|---|---|---|---|---|---|
BRAF | V600E | Biliary Tract Cancer, Diffuse Glioma, Encapsulated Glioma, Ganglioglioma, Pleomorphic Xanthoastrocytoma, Pilocytic Astrocytoma | Dabrafenib + Trametinib | 2 | 1 | FDA approval of dabrafenib + trametinib in solid tumors |
ERBB2 | Oncogenic Mutations | Non-Small Cell Lung Cancer | Trastuzumab Deruxtecan | 2 | 1 | FDA approval of trastuzumab deruxtecan in non-small cell lung cancer |
FGFR1 | Fusions | Myeloid/Lymphoid Neoplasms with FGFR1 Rearrangement | Pemigatinib | 2 | 1 | FDA approval of pemigatinib in myeloid/lymphoid neoplasms |
Level | Gene | Mutation | Cancer Type | Drug(s) | Evidence |
---|---|---|---|---|---|
3A | KMT2A | Fusions | B-Lymphoblastic Leukemia/Lymphoma, Acute Myeloid Leukemia | SNDX-5613 (Menin inhibitor) | PMID: 31855575; Abstract: Stein et al. Abstract# 699, ASH 2021 |
3A | NPM1 | Oncogenic Mutations | Acute Myeloid Leukemia | SNDX-5613 (Menin inhibitor) | PMID: 31855575; Abstract: Stein et al. Abstract# 699, ASH 2021 |
Gene | Mutation | Cancer Type | Drug(s) | Previous Level | Current Level | Reason |
---|---|---|---|---|---|---|
ALK | Fusions | Inflammatory Myofibroblastic Tumor | Crizotinib | 2 | 1 | FDA approval of crizotinib in inflammatory myofibroblastic tumor |
Gene | Mutation | Cancer Type | Current Level of Evidence | Drug(s) remaining in OncoKB™ | Drug(s) added to OncoKB™ | Evidence |
---|---|---|---|---|---|---|
NRG1 | Fusions | Non-Small Cell Lung Cancer | 3A | Zenocutuzumab | Seribantumab (Level 3A) | Abstract: Carrizosa et al. Abstract# 3006, ASCO 2022 |
Gene | Mutation | Cancer Type | Drug(s) | Previous Level | Current Level | Reason |
---|---|---|---|---|---|---|
BRAF | V600E | Biliary Tract Cancer | Dabrafenib + Trametinib | 3A | 2 | Listing in Hepatobiliary NCCN v1.2022; PMID: 32818466, 32758030 |
Gene | Mutation | Cancer Type | Current Level of Evidence | Drug(s) remaining in OncoKB™ | Drug(s) added to OncoKB™ | Evidence |
---|---|---|---|---|---|---|
ALK | Fusions | Inflammatory Myofibroblastic Tumor | 2 | Crizotinib, Ceritinib, Brigatinib | Brigatinib (Level 2) | Listing in Soft Tissue Sarcoma NCCN v1.2022; PMID: 28713152, 32868646, 33007314 |
ROS1 | Fusions | Non-Small Cell Lung Cancer | 1 | Crizotinib, Entrectinib | Repotrectinib (Level 3A) | FDA breakthrough therapy designation; Abstract: Cho et al. Abstract# MA11.07, IASLC 2021 |
NTRK1, NTRK2, NTRK3 | Fusions | All Solid Tumors | 1 | Larotrectinib, Entrectinib | Repotrectinib (Level 3A) | FDA breakthrough therapy designation; Abstract: Cho et al. Abstract# MA11.07, IASLC 2021 |
Gene | Mutation | Cancer Type | Current Level of Evidence | Drug(s) remaining in OncoKB™ | Drug(s) added to OncoKB™ | Evidence |
---|---|---|---|---|---|---|
EGFR | S768I, L861Q, G719 | Non-Small Cell Lung Cancer | 1 | Afatinib | Osimertinib (Level 2) | Listing in NSCLC NCCN v1.2022; PMID: 31825714 |
ROS1 | Fusions | Non-Small Cell Lung Cancer | 1 | Crizotinib, Entrectinib | Ceritinib (Level 2) | Listing in NSCLC NCCN v1.2022; PMID: 28520527 |
ROS1 | Fusions | Non-Small Cell Lung Cancer | 1 | Crizotinib, Entrectinib | Lorlatinib (Level 2) | Listing in NSCLC NCCN v1.2022; PMID: 31669155 |
MET | Amplifications | Non-Small Cell Lung Cancer | 2 | Crizotinib | Capmatinib (Level 2) | Listing in NSCLC NCCN v1.2022; PMID: 32877583 |
MET | Amplifications | Non-Small Cell Lung Cancer | 2 | Crizotinib | Tepotinib (Level 2) | Listing in NSCLC NCCN v1.2022; Abstract: Le et al. Abstract# 9021, ASCO 2021 |
KRAS | G12C | Pancreatic Cancer | 3A | Adagrasib | Sotorasib (Level 3A) | Abstract: Strickler et al. Abstract# 360490, ASCO GI 2022 |
FGFR2 | Fusions | Cholangiocarcinoma | 1 | Infigratinib, Pemigatinib | Futibatinib (Level 3A) | Abstract: Goyal et al. Abstract# CT010, AACR 2021 |
Level | Gene | Mutation | Cancer Type | Drug(s) | Evidence |
---|---|---|---|---|---|
2 | BRCA2 | Oncogenic Mutations | Uterine Sarcoma | Olaparib, Rucaparib, Niraparib | Listing in Uterine cancer NCCN v1.2022; PMID: 33970096 |
2 | PALB2 | Oncogenic Mutations | Pancreatic Cancer | Rucaparib | Listing in Pancreatic cancer NCCN v1.2022; PMID: 33970687, 34351646, 30051098 |
Gene | Mutation | Cancer Type | Drug(s) | Previous Level | Current Level | Reason |
---|---|---|---|---|---|---|
BRCA1, BRCA2 | Oncogenic Mutations | Pancreatic Cancer | PARPi | 3A | 2 | Listing of Rucaparib in Pancreatic cancer NCCN v1.2022; PMID: 33970687, 34351646, 30051098 |
Level | Gene | Mutation | Cancer Type | Drug(s) | Evidence |
---|---|---|---|---|---|
3A | EGFR | Exon 19 deletion, Exon 19 insertion, G719, L858R, L861Q, S768I | Non-Small Cell Lung Cancer | Patritumab Deruxtecan | FDA Breakthrough Therapy designation; PMID: 34548309 |
3A | EGFR | Exon 20 in-frame insertions | Non-Small Cell Lung Cancer | CLN-081 | FDA Breakthrough Therapy designation; Abstract: Piotrowska et al. Abstract# 9077, ASCO 2021. |
3A | ERBB2 | Oncogenic Mutations | Non-Small Cell Lung Cancer | Trastuzumab + Pertuzumab + Docetaxel | PMID: 35073148 |
3A | KRAS | G12C | Gastrointestinal Cancers (excluding Colorectal and Appendiceal Cancer), Pancreatic Adenocarcinoma | Adagrasib | Abstract: Bekaii-Saab et al. Abstract# 519, ASCO GI Symposium, 2022. |
Level | Gene | Mutation | Cancer Type | Drug(s) | Evidence |
---|---|---|---|---|---|
4 | STK11 | Oncogenic Mutations | Non-Small Cell Lung Cancer | Bemcentinib + Pembrolizumab | Abstract: Li et al. Abstract # 602, JITC 2021 |
Level | Gene | Mutation | Cancer Type | Drug(s) | Evidence |
---|---|---|---|---|---|
1 | ABL1 | T315I | Chronic Myelogenous Leukemia | Asciminib | FDA approval of Asciminib; Abstract: Hochhaus et al. Abstract #LBA-4, ASH 2020 |
3A | IDH1 | R132 | Glioma | Ivosidenib | PMID: 29670690, 32530764 |
3A | KRAS | G12C | Colorectal Cancer | Adagrasib, Adagrasib + Cetuximab | Abstract: Weiss et al. Abstract# LBA6, ESMO 2021 |
4 | MDM2 | Amplification | Dedifferentiated Liposarcoma, Well-Differentiated Liposarcoma | Milademetan | PMID: 23400593 |
Gene | Mutation | Cancer Type | Drug(s) | Previous Level | Current Level | Reason |
---|---|---|---|---|---|---|
ABL1 | BCR-ABL1 Fusion | Chronic Myelogenous Leukemia | Asciminib | 3A | 1 | FDA approval of Asciminib; PMID: 34407542 |
BRCA1, BRCA2 | Oncogenic Mutations | Breast Cancer | Olaparib, Talazoparib | 2 | 3A | Strict adherence to FDA drug labels for olaparib and talazoparib |
MET | Y1003mut | Non-Small Cell Lung Cancer | Tepotinib, Capmatinib | 1 | 3A | Strict adherence to FDA drug labels for tepotinib and capmatinib |
MET | Y1003mut | Non-Small Cell Lung Cancer | Crizotinib | 2 | 3A | Strict adherence to listing in NCCN Non-Small Cell Lung Cancer v7.2021 |
Level | Gene | Previous Variant Annotation | Current Variant Annotation | Cancer Type | Drug | Evidence |
---|---|---|---|---|---|---|
1 | ALK | Oncogenic Mutations | Fusions | Non-Small Cell Lung Cancer | Brigatinib | FDA drug label for brigatinib and adherence to OncoKB™ SOP v2.2 |
2 | BRAF | V600 | V600 (Excluding V600E, V600K) | Melanoma | Binimetinib + Encorafenib, Dabrafenib + Trametinib, Cobimetinib + Vemurafenib | The NCCN Melanoma: Cutaneous v2.2021 lists “BRAF V600” and is not limited to V600E/K. Therefore, according to the OncoKB™ SOP v2.2 BRAF V600 is considered Level 2, while V600E/K are Level 1. |
2 | EZH2 | Oncogenic Mutations | Oncogenic Mutations (Excluding Y646F, A692V, Y646C, Y646S, Y646N, Y646H, A682G) | Follicular Lymphoma | Tazemetostat | The NCCN B-cell lymphoma v5.2021 lists “EZH2 mutation” and is not limited to the mutations listed in the FDA-approved CDx. Therefore, according to the OncoKB™ SOP v2.2 EZH2 Oncogenic Mutations are considered Level 2, with the exception of those mutations listed in the CDx, which are Level 1. |
2 | PIK3CA | Oncogenic Mutations | Oncogenic Mutations (Excluding E545G, Q546E, E545A, H1047R, C420R, H1047Y, Q546R, H1047L, E542K, E545D, E545K) | Breast Cancer | Alpelisib+Fulvestrant | The NCCN Breast Cancer V8.2021 lists “PIK3CA activating mutation” and is not limited to the mutations listed in the FDA-approved CDx. Therefore, PIK3CA Oncogenic Mutations by OncoKB™ SOP v2.2 are considered Level 2, with the exception of those mutations listed in the CDx, which are Level 1. |
Level | Gene | Mutation | Previous Cancer Type | Current Cancer Type | Drug | Evidence |
---|---|---|---|---|---|---|
3A | PTCH1 | Truncating Mutations | Embryonal Tumor | Medulloblastoma | Sonidegib, Vismodegib | PMID: 24523439, 32923880, 26169613, 31362788, 29515801 |
Level | Gene | Mutation | Cancer Type | Drug | Evidence |
---|---|---|---|---|---|
2 | BRAF | V600E | Encapsulated Glioma, Diffuse Glioma | Dabrafenib + Trametinib, Vemurafenib + Cobimetinib | Listing in the CNS NCCN v1.2021; PMID: 28984141, 29380516, 26287849, 30351999 |
2 | BRAF | V600 | Langerhans Cell Histiocytosis | Vemurafenib, Dabrafenib | Listing in Histiocytic Neoplasms NCCN v2.2021; PMID: 30867592 |
2 | BRAF | Oncogenic Mutations, excluding V600 | Erdheim-Chester Disease | Cobimetinib, Trametinib | Listing in Histiocytic Neoplasms NCCN v2.2021; PMID: 30867592 |
Langerhans Cell Histiocytosis | Listing in Histiocytic Neoplasms NCCN v2.2021; PMID: 30867592, 32991018 | ||||
Rosai-Dorfman Disease | Listing in Histiocytic Neoplasms NCCN v2.2021; PMID: 29236635 | ||||
2 | ARAF, RAF1, KRAS, NRAS, MAP2K1, MAP2K2 | Oncogenic Mutations | Erdheim-Chester Disease | Cobimetinib, Trametinib | Listing in Histiocytic Neoplasms NCCN v2.2021; PMID: 30867592 |
Langerhans Cell Histiocytosis | Listing in Histiocytic Neoplasms NCCN v2.2021; PMID: 30867592, 32991018 | ||||
Rosai-Dorfman Disease | Listing in Histiocytic Neoplasms NCCN v2.2021; PMID: 29236635 | ||||
3A | BRAF | V600 | Histiocytosis | Vemurafenib, Dabrafenib | PMID: 25209580, 31213430, 31376203 |
3A | KRAS | Oncogenic Mutations | Histiocytosis | Cobimetinib, Trametinib | PMID: 30361829 |
3A | NRG1 | Fusions | All Solid Tumors | Zenocutuzumab | Abstract: Schram et al. Abstract# 3003, ASCO 2021 |
R2 | BTK | C481R, C481F, C481Y, T474I, T474S, T316A | Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma | Ibrutinib | PMID: 28049639, 29381098, 28418267, 32670873; Abstract: Woyach et al. Abstract# 642-CLL, ASH 2019 |
Level | Gene | Mutation | Cancer Type | Drug(s) | Evidence |
---|---|---|---|---|---|
R2 | EGFR | G724S | Non-Small Cell Lung Cancer | Osimertinib | PMID: 28838405, 30405134, 30228210, 30796031 |
Gene | Mutation | Cancer Type | Drug(s) | Previous Level | Current Level | Reason |
---|---|---|---|---|---|---|
EGFR | Exon 20 in-frame insertions | Non-Small Cell Lung Cancer | Mobocertinib | 3A | 1 | FDA approval of Mobocertinib; Abstract: Ramalingham et al. Abstract # 9014, ASCO 2021 |
Gene | Mutation | Cancer Type | Drug(s) | Previous Level | Current Level | Reason |
---|---|---|---|---|---|---|
IDH1 | R132 | Cholangiocarcinoma | Ivosidenib | 3A | 1 | FDA approval of Ivosidenib; PMID: 32416072 |
Gene | Mutation | Cancer Type | Drug(s) | Previous Level | Current Level | Reason |
---|---|---|---|---|---|---|
KIT | D816 | Mastocytosis | Avapritinib | 3A | 1 | FDA approval of Avapritinib; Abstract: Gotlib et al. Abstract# 634, ASH 2020; Abstract: DeAngelo et al. Absract# CT023, AACR 2021. |
EGFR | Exon 20 in-frame insertions | Non-Small Cell Lung Cancer | Amivantamab | 3A | 1 | FDA approval of Amivantamab; Abstract: Sabari et al. Abstract# OA04.04, WCLC, 2021. |
Level | Gene | Mutation | Cancer Type | Drug(s) | Evidence |
---|---|---|---|---|---|
1 | ERBB2 | Amplification | Esophagogastric Cancer | Pembrolizumab + Trastuzumab + Chemotherapy | FDA approval of Pembrolizumab + Trastuzumab + Chemotherapy; PMID: 33167735 |
1 | FGFR2 | Fusions | Cholangiocarcinoma | Infigratinib | FDA approval of Infigratinib; Abstract: Javle et al. Abstract# 265, ASCO 2021 |
4 | ARID1A | Truncating Mutations | All Solid Tumors | Tazemetostat | PMID: 25686104, 32506298 |
4 | ARID1A | Truncating Mutations | All Solid Tumors | PLX2853 | PMID: 29760405, 31913353 |
Gene | Mutation | Cancer Type | Drug(s) | Previous Level | Current Level | Reason |
---|---|---|---|---|---|---|
KRAS | G12C | Non-Small Cell Lung Cancer | Sotorasib | 3A | 1 | FDA approval of Sotorasib; PMID: 34096690 |
Level | Gene | Cancer Type | Drug | Previous Biomarker Association | Current Biomarker Association | Evidence |
---|---|---|---|---|---|---|
1 | EZH2 | Follicular Lymphoma | Tazemetostat | Oncogenic Mutations | Y646N, Y646F, Y646H, Y646S, Y646C, A682G, A692V | P200014 |
1 | IDH1 | AML | Ivosidenib | Oncogenic Mutations | R132C, R132H, R132G, R132S, R132L | P170041 |
1 | IDH2 | AML | Enasidenib | Oncogenic Mutations | R140Q, R140L, R140G, R140W, R172K, R172M, R172G, R172S, R172W | P170005 |
1 | PIK3CA | Breast Cancer | Alpelisib + Fulvestrant | Oncogenic Mutations | C420R, E542K, E545A, E545D, E545G, E545K, Q546E, Q546R, H1047L, H1047R, H1047Y | FoundationOne CDx - P170019/S006; Therascreen - P190001; FoundationOne Liquid CDx - P200006, P200016 |
Level | Gene | Mutation | Cancer Type | Drug(s) | Evidence |
---|---|---|---|---|---|
2 | IDH1 | Oncogenic Mutations | Chondrosarcoma | Ivosidenib | Listing in Bone Cancer NCCN v1.2021; PMID: 32208957 |
2 | JAK2 | Fusions | Myeloid/Lymphoid Neoplasms with Eosinophilia and Rearrangement of PDGFRA/PDGFRB or FGFR1 or with PCM1-JAK2 | Ruxolitinib, Fedratinib | Listing in Myeloid/Lymphoid Neoplasms with Eosinophilia and Tyrosine Kinase Fusion Genes NCCN v3.2021; PMID: 32279331 |
2 | FGFR1 | Fusions | Myeloid/Lymphoid Neoplasms with FGFR1 Rearrangement | Pemigatinib | Listing in Myeloid/Lymphoid Neoplasms with Eosinophilia and Tyrosine Kinase Fusion Genes NCCN v3.2021; PMID: 32472305; Abstract: Verstovsek et al, Abstract# 690, ASH 2018. |
3A | EGFR | Exon 20 in-frame insertions | Non-Small Cell Lung Cancer | Mobocertinib | PMID: 33632775 |
3A | EGFR | Exon 20 in-frame insertions | Non-Small Cell Lung Cancer | Amivantamab | Abstract: Sabari et al. Abstract# OA04.04, WCLC 2020. |
3A | KRAS | G12C | Non-Small Cell Lung Cancer | Adagrasib | Abstract: Janne et al. Abstract# LBA-03, EORTC 2020. |
3A | HRAS | Oncogenic Mutations | Bladder Urothelial Carcinoma | Tipifarnib | PMID: 32636318 |
3A | BRAF | V600E | Biliary Tract Cancer | Dabrafenib + Trametinib | PMID: 32818466 |
3A | TSC2 | Oncogenic Mutations | Perivascular Epithelioid Cell Tumor | ABI-009 | Abstract: Wagner et al. Abstract# 11005, ASCO 2019.; Abstract: Wagner et al. Abstract# 11516, ASCO 2020. |
Level | Gene | Mutation | Cancer Type | Drug(s) | Evidence |
---|---|---|---|---|---|
1 | MET | Exon 14 Deletion | Non-Small Cell Lung Cancer | Tepotinib | FDA approval of Tepotinib; PMID: 32469185 |
2 | ERBB2 | Amplification | Colorectal Cancer | Trastuzumab Deruxtecan | Listing in Colorectal Cancer NCCN, v2.2021; Abstract: Siena et al. Abstract# 4000, ASCO 2020. |
2 | ERBB2 | Oncogenic Mutations | Non-Small Cell Lung Cancer | Trastuzumab Deruxtecan | Listing in NSCLC NCCN, v2.2021; Abstract: Smit et al. Abstract# 9504, ASCO 2020. |
2 | ALK | Fusions | Inflammatory Myofibroblastic Tumor | Brigatinib | Listing in Soft Tissue Sarcoma NCCN, v1.2021; PMID: 27836716 |
4 | KIT | D816, D820, N822, Y823D, C809G, A829P | Gastrointestinal Stromal Tumors | Nilotinib | PMID: 19467857, 21456006 |
4 | KIT | D816, D820, N822, Y823D, C809G, A829P | Gastrointestinal Stromal Tumors | Pazopanib | PMID: 24356634 |
R1 | NTRK3 | G623R, G696A, F617L | All Solid Tumors | Larotrectinib | Inclusion as resistance mutations in FDA drug label |
R2 | NTRK1 | G623R | All Solid Tumors | Entrectinib | PMID: 28751539, 28751539, 26546295; Abstract: Drilon et al. Abstract# 4000, AACR 2019 |
Gene | Mutation | Cancer Type | Drug(s) | Previous Level | Current Level |
---|---|---|---|---|---|
NTRK1 | G623R | All Solid Tumors | Larotrectinib | R2 | R1 |
KIT | D816, D820, N822, Y823D, C809G, A829P | Gastrointestinal Stromal Tumors | Sorafenib | None | 2 |
CDK4 | Amplification | Dedifferentiated Liposarcoma, Well-Differentiated Liposarcoma | Palbociclib, Abemaciclib | None | 4 |
Level | Gene | Mutation | Cancer Type | Drug(s) | Evidence |
---|---|---|---|---|---|
1 | ALK | Fusions | Anaplastic Large-Cell Lymphoma | Crizotinib | FDA approval of Crizotinib; PMID: 23598171, 28032129, 29352732 |
1 | ERBB2 | Amplification | Breast Cancer | Margetuximab + Chemotherapy | FDA approval of Margetuximab + Chemotherapy; Abstract: Rugo et al. Abstract # 1000, ASCO 2019 |
1 | ERBB2 | Amplification | Gastric or Gastroesophageal Adenocarcinoma | Trastuzumab Deruxtecan | FDA-approval of Trastuzumab deruxtecan; PMID: 32469182 |
Gene | Mutation | Cancer Type | Drug(s) | Previous Level | Current Level |
---|---|---|---|---|---|
RET | Fusions | Non-Small Cell Lung Cancer | Vandetanib | 2 | 3A |
NRAS | Oncogenic Mutations | Melanoma | Binimetinib + Ribociclib | 3A | 4 |
MET | Amplification | Renal Cell Carcinoma | Cabozantinib | 2 | None |
CDK4 | Amplification | Dedifferentiated Liposarcoma, Well-Differentiated Liposarcoma | Palbociclib, Abemaciclib | 2 | None |
KIT | A829P, C809G, D816, D820, N822, Y823D | Gastrointestinal Stromal Tumor | Sorafenib | 2 | None |
KIT | Oncogenic Mutations | Thymic Tumor | Sunitinib | 2 | None |
Level | Gene | Mutation | Cancer Type | Drug(s) | Evidence |
---|---|---|---|---|---|
1 | RET | Fusions | Thyroid Cancer | Pralsetinib | FDA-approval of Pralsetinib; Abstract: Subbiah et al. Abstract# 109, ASCO 2020 |
Gene | Mutation | Cancer Type | Drug(s) | Previous Level | Current Level | Reason |
---|---|---|---|---|---|---|
RET | Oncogenic Mutations | Medullary Thyroid Cancer | Pralsetinib | 3A | 1 |
Level | Gene | Mutation | Cancer Type | Drug | Evidence |
---|---|---|---|---|---|
R1 | ABL1 | V299L, F317L, G250E | CML | Bosutinib | NCCN v2.2021 CML; PMID: 21865346, 22371878 |
BLL | NCCN v2.2020 ALL; PMID: 26040495 | ||||
F317V/I/C/L, T315A, V299L | CML | Dasatinib | NCCN v2.2021 CML; PMID: 17785585, 19589924, 19779040, 17710227, 17339191, 17114651 | ||
BLL | NCCN v2.2020 ALL; PMID: 17496201, 20131302, 17339191 | ||||
E255K/V, F359C/I/V, Y253H, G250E | CML | Nilotinib | NCCN v2.2021 CML; PMID: 16775235, 17785585, 23502220, 19652056, 19589924 | ||
BLL | NCCN v2.2020 ALL; PMID: 16775235, 17785585, 23502220, 19652056, 19589924 | ||||
V299L, G250E, F317V/I/C/L, T315A, E255K/V, F359C/I/V, Y253H | CML | Imatinib | NCCN v2.2021 CML; PMID: 17189410, 20010464, 19925053, 17189410, 17785585, 12623848 | ||
BLL | NCCN v2.2020 ALL; PMID: 17189410, 17405907, 11861307 |
Level | Gene | Mutation | Cancer Type | Drug(s) | Evidence |
---|---|---|---|---|---|
R1 | BTK | C481S | Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma | Ibrutinib | Listing in NCCN v4.2020 CLL; PMID: 24869598, 28418267 |
Level | Gene | Mutation | Cancer Type | Drug | Evidence |
---|---|---|---|---|---|
1 | KIT | Select Oncogenic Mutations | Gastrointestinal Stromal Tumors | Ripretinib | FDA-approval of Ripretinib; PMID: 32511981 |
1 | BRAF | V600 | Melanoma | Vemurafenib + Cobimetinib + Atezulizumab | FDA-approval of Atezulizumab; PMID: 32534646 |
2 | PDGFRA | Oncogenic Mutations | Gastrointestinal Stromal Tumors | Ripretinib | Listing in 2.2020 Soft Tissue Sarcoma NCCN; PMID: 32511981 |
Regorafenib | Listing in 2.2020 Soft Tissue Sarcoma NCCN; PMID: 23177515, 27371698 | ||||
Sunitinib | Listing in 2.2020 Soft Tissue Sarcoma NCCN; PMID: 17046465, 19282169, 25641662 | ||||
3A | BRCA1, BRCA2 | Oncogenic Mutations | Pancreatic Adenocarcinoma | Olaparib | FDA-approval of Olaparib in the germline setting; PMID: 31157963, 32444418 |
Level | Gene | Mutation | Cancer Type | Drug(s) | Evidence |
---|---|---|---|---|---|
1 | Other Biomarkers | Tumor Mutational Burden - High | All Solid Tumors | Pembrolizumab | Abstract: Marabelle et al. Abstract# 1192O, ESMO 2019, FDA-approval of Pembrolizumab |
Level | Gene | Mutation | Cancer Type | Drug(s) | Evidence |
---|---|---|---|---|---|
1 | SMARCB1 | Deletion | Epithelioid Sarcoma | Tazemetostat | Abstract: Stacchiotti et al. Abstract# 11003, JCO 2019, FDA-approval of Tazemetostat |
Gene | Mutation | Cancer Type | Drug(s) | Previous Level | Current Level | Reason |
---|---|---|---|---|---|---|
EZH2 | A682G, A692V, Y646C, Y646F, Y646H, Y646N, Y646S | Follicular Lymphoma | Tazemetostat | 3A | 1 |
Level | Gene | Mutation | Cancer Type | Drug(s) | Evidence |
---|---|---|---|---|---|
1 | BRCA1, BRCA2, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, RAD51B, RAD51C, RAD51D, RAD54L | Oncogenic Mutations | Prostate Cancer | Olaparib | PMID: 32343890, FDA-approval of Olaparib |
1 | BRCA1, BRCA2 | Oncogenic Mutations | Prostate Cancer | Rucaparib | Abstract: Abida et al. Abstract# 846PD, ESMO 2019, FDA-approval of Rucaparib |
Gene | Mutation | Cancer Type | Drug(s) | Previous Level | Current Level | Reason |
---|---|---|---|---|---|---|
ATM | Oncogenic Mutations | Prostate Cancer | Olaparib | 4 | 1 | PMID: 32343890, FDA-approval of Olaparib |
Level | Gene | Mutation | Cancer Type | Drug(s) | Evidence |
---|---|---|---|---|---|
1 | FGFR2 | Fusions | Cholangiocarcinoma | Pemigatinib | PMID: 32203698, FDA-approval of Pemigatinib |
1 | RET | Fusions | Thyroid Cancer | Selpercatinib | |
1 | ERBB2 | Amplification | Breast Cancer | Tucatinib + Trastuzumab + Capecitabine | PMID: 31825569, FDA-approval of Tucatinib |
1 | ERBB2 | Amplification | Breast Cancer | Trastuzumab Deruxtecan | PMID: 31825192, FDA-approval of Trastuzumab Deruxtecan |
2 | BRAF | V600E | Pilocytic Astrocytoma, Pleomorphic Xanthoastrocytoma and Ganglioglioma | Dabrafenib + Trametinib, Vemurafenib + Cobimetinib | Listing in 1.2020 CNS NCCN; PMID: 28984141, 29380516, 26287849, 30351999, 30120137 |
Gene | Mutation | Cancer Type | Drug(s) | Previous Level | Current Level | Reason |
---|---|---|---|---|---|---|
MET | Exon 14 Deletion | Non-Small Cell Lung Cancer | Capmatinib | 3A | 1 | |
RET | Fusions | Non-Small Cell Lung Cancer | Selpercatinib | 3A | 1 | |
RET | Oncogenic Mutations | Medullary Thyroid Cancer | Selpercatinib | 3A | 1 |
Level | Gene | Mutation | Cancer Type | Drug(s) | Evidence |
---|---|---|---|---|---|
1 | BRAF | V600E | Colorectal Cancer | Encorafenib + Cetuximab | PMID: 31566309, FDA-approval of Encorafenib + Cetuximab |
1 | NF1 | Oncogenic Mutations | Neurofibroma | Selumetinib | PMID: 28029918, 32187457, FDA-approval of Selumetinib |
2 | BRAF | V600E | Colorectal Cancer | Encorafenib + Panitumumab | Listing in 2.2020 Colon Cancer NCCN; PMID: 29431699, 31566309 |
2 | ERBB2 | Amplification | Colorectal Cancer | Trastuzumab + Lapatinib | Listing in 2.2020 Colon Cancer NCCN; PMID: 27108243 |
2 | ERBB2 | Amplification | Colorectal Cancer | Trastuzumab + Pertuzumab | Listing in 2.2020 Colon Cancer NCCN; PMID: 30857956 |
Level | Gene | Mutation | Cancer Type | Drug(s) | Evidence |
---|---|---|---|---|---|
1 | PDGFRA | D842V, D842Y, D842_H845del, D842_H845insV | Gastrointestinal Stromal Tumor | Avapritinib | Abstract: Heinrich et al. Abstract # 11022, ASCO 2019; FDA-approval of Avapritinib; 2019 |
3A | BRCA2 | Oncogenic Mutations | Pancreatic Adenocarcinoma | Rucaparib | PMID: 30051098; Abstract: Reiss Binder et al. Abstract# CT234, AACR 2019 |
4 | EGFR | L718V | Non-Small Cell Lung Cancer | Afatinib | PMID: 29571986, 31757379 |
R2 | EGFR | L718V | Non-Small Cell Lung Cancer | Osimertinib | PMID: 29568384, 29571986, 31301016, 31757379 |
R2 | KIT | A829P | Gastrointestinal Stromal Tumor | Imatinib | PMID: 18955458, 25239608, 31085175 |
R2 | KIT | A829P | Gastrointestinal Stromal Tumor | Sunitinib | PMID: 31085175 |
Level | Gene | Mutation | Cancer Type | Drug(s) | Evidence |
---|---|---|---|---|---|
1 | FLT3 | D835, I836 | AML | Gilteritinib | PMID: 28516360, 28645776 ; FDA-approval of Gilteritinib |
1 | MSI-H | Colorectal Cancer | Nivolumab + Ipilimumab | PMID: 29355075; FDA-approval of Nivolumab + Ipilimumab | |
1 | ROS1 | Fusions | NSCLC | Entrectinib | PMID: 28183697, Abstract: Drilon et al. Abstract# CT060, AACR 2017 ; FDA-approval of Entrectinib |
3A | KRAS | G12C | NSCLC | AMG-510 | Abstract: Govindan et al. ESMO 2019 |
Gene | Mutation | Cancer Type | Drug(s) | Previous Level | Current Level | Reason |
---|---|---|---|---|---|---|
NTRK1, NTRK2, NTRK3 | Fusions | All Solid Tumors | Entrectinib | 3A | 1 | FDA-approval of Entrectinib |
ERBB2 | Oncogenic Mutations | NSCLC | Ado-trastuzumab Emtansine | 3A | 2A | Listing in 1.2020 Non-Small Cell Lung Cancer NCCN |
IDH1 | Oncogenic Mutations | Cholangiocarcinoma | Ivosidenib | 2B | 3A | Abstract: Abou-Alfa et al. Abstract# LBA10_PR, ESMO 2019 |
PIK3CA | Oncogenic Mutations | Breast Cancer | Alpelisib | 3A | None | Alpelisib in combination with fulvestrant is FDA-approved to treat patients with PIK3CA mutant breast cancer |
Level | Gene | Mutation | Cancer Type | Drug(s) | Evidence |
---|---|---|---|---|---|
3A | EZH2 | Oncogenic Mutations | Follicular Lymphoma | Tazemetostat | Abstract: Morschhauser et al. Abstract# S100, EHA 2018. |
Level | Update |
---|---|
1 |
|
2A |
|
Level | Gene | Mutation | Cancer Type | Drug |
---|---|---|---|---|
1 | ABL1 | BCR-ABL1 fusion | B-Lymphoblastic Leukemia/Lymphoma (BLL) | Ponatinib |
Chronic Myelogenous Leukemia (CML) | Bosutinib | |||
T315I | BLL, CML | Ponatinib | ||
FLT3 | Internal tandem duplications (ITD) | Acute Myeloid Leukemia (AML) | Gilteritinib | |
Oncogenic Mutations | Midostaurin + High Dose Chemotherapy | |||
R1 | ABL1 | T315I | BLL, CML | Imatinib, Dasatinib, Nilotinib, Bosutinib |
2A | ABL1 | BCR-ABL1 fusion | BLL | Bosutinib, Nilotinib |
E255K, E255V, F317C, F317I, F317L, F317V, F359C, F359I, F359V, T315A, Y253H | BLL, CML | Bosutinib | ||
E255K, E255V, F359C, F359I, F359V, Y253H | Dasatinib | |||
F317C, F317I, F317L, F317V, T315A, V299L | Nilotinib | |||
3A | ABL1 | BCR-ABL1 fusion | CML | Asciminib |
E255K, E255V, F359C, F359I, F359V, Y253H | BLL, CML | Dasatinib | ||
F317C, F317I, F317L, F317V, T315A, V299L | Nilotinib | |||
FLT3 | ITD | AML | Crenolanib, Quizartinib | |
4 | SF3B1 | Oncogenic Mutations | AML, Chronic Myelomonocytic Leukemia (CMML), Myelodysplastic Syndrome (MDS) | H3B-8800 |
SRSF2 | ||||
U2AF1 | ||||
ZRSR2 |
Level | Update |
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1 |
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4 |
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Level | Update |
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1 |
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Level | Update |
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1 |
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2A |
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3A |
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4 |
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Level | Update |
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2A |
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Level | Update |
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4 |
|
Level | Update |
---|---|
3A |
|
Level | Update |
---|---|
1 |
|
Level | Update |
---|---|
1 |
|
3A |
|
Gene | Mutation | Cancer Type | Drug |
---|---|---|---|
ATM | Oncogenic Mutations | Prostate Cancer | Olaparib |
BRAF | D287H, D594A, D594G, D594H, D594N, F595L, G464E, G464V, G466A, G466E, G466V, G469A, G469E, G469R, G469V, G596D, G596R, K601N, K601T, L597Q, L597V, N581I, N581S, S467L, V459L | All Tumors | PLX8394 |
CDKN2A | Oncogenic Mutations | All Tumors | Abemaciclib, Palbociclib, Ribociclib |
EGFR | A289V, R108K, T263P | Glioma | Lapatinib |
EGFR | Amplification | Glioma | Lapatinib |
EWSR1 | EWSR1-FLI1 Fusion | Ewing Sarcoma | TK216 |
FGFR1 | Oncogenic Mutations | All Tumors | AZD4547, BGJ398, Debio1347, Erdafitinib |
FGFR2 | Oncogenic Mutations | All Tumors | AZD4547, BGJ398, Debio1347, Erdafitinib |
KRAS | Oncogenic Mutations | All Tumors | KO-947, LY3214996, Ravoxertinib, Ulixertinib |
MTOR | Oncogenic Mutations | All Tumors | Everolimus, Temsirolimus |
NF1 | Oncogenic Mutations | All Tumors | Cobimetinib, Trametinib |
PTEN | Oncogenic Mutations | All Tumors | AZD8186, GSK2636771 |
SMARCB1 | Oncogenic Mutations | All Tumors | Tazemetostat |
Level | Update |
---|---|
1 |
|
3A |
|
Level | Update |
---|---|
1 |
|
2A |
|
3A |
|
4 |
|
Level | Update |
---|---|
1 |
|
2A |
|
3A |
|
4 |
|
We are happy to announce the first release of OncoKB™, a knowledge base for precision medicine. Our goal is to comprehensively annotate the oncogenic effect of mutations observed in cancer, as well as their therapeutic implications. This release contains information about almost 3,000 alterations in 418 cancer genes. For each alteration, we categorize the biological and clinical effect, along with citations of the source of the information, and, when available, the therapeutic implications of a alteration. We have focussed on FDA-approved (Level 1) or guideline-listed (Level 2) biomarkers, as well as biomarkers that with clinical evidence for sensitivity and for which therapies are currently explored in clinical trials (Level 3). See the Levels of Evidence and Actionable Genes pages for more information.
We have also integrated information from OncoKB™ into the cBioPortal for Cancer Genomics. When exploring alterations in cbioportal.org, you will see annotations from OncoKB™ when available. Example of a lung cancer case.