diff --git a/content/somatic_variant.tsv b/content/somatic_variant.tsv index 2e8477b..aa8b849 100644 --- a/content/somatic_variant.tsv +++ b/content/somatic_variant.tsv @@ -250,6 +250,12 @@ GATA3 10 8106058 8106058 T A c.881T>A p.M294K Missense 4 Breast Cancer Invasiv IDH1 Acute Myeloid Leukemia Relapsed or refractory Acute Myeloid Leukemia AML Ivosidenib IDH1 inhibition Targeted therapy 1 FDA-Approved "The U.S. Food and Drug Administration (FDA) granted approval for ivosidenib, a small molecule inhibitor of isocitrate dehydrogenase (IDH)1 on July 20, 2018, for treatment of adults with relapsed or refractory acute myeloid leukemia (R/R AML) with susceptible IDH1 mutation as detected by an FDA-approved test." FDA "Agios Pharmaceuticals, Inc.. Tibsovo (ivosidenib) [package insert]. U.S. Food and Drug Administration website. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211192s001lbl.pdf. Revised October 2020. Accessed November 12, 2020." https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211192s001lbl.pdf NCT02074839 11/12/20 IDH1 Glioma Glioma GNOS Alkylating chemotherapy Alkylating chemotherapy Chemotherapy 1 Guideline Mutation of IDH1 is associated with a survival benefit in patients treated with alkylating chemotherapy (but not untreated patients). Guideline "National Comprehensive Cancer Network. Central Nervous System Cancers NCCN Evidence Blocks for Gliomas (Version 1.2016). Accessed November 5, 2016." https://www.nccn.org/professionals/physician_gls/pdf/cns_blocks.pdf 11/3/17 IDH1 Glioma Glioma GNOS 1 Guideline Mutation of IDH1 is associated with a survival benefit in patients treated with alkylating chemotherapy (but not untreated patients). Guideline "National Comprehensive Cancer Network. Central Nervous System Cancers NCCN Evidence Blocks for Gliomas (Version 1.2016). https://www.nccn.org/professionals/physician_gls/pdf/cns_blocks.pdf. Accessed November 5, 2016." https://www.nccn.org/professionals/physician_gls/pdf/cns_blocks.pdf 11/3/17 +IDH1 2 209113112 209113112 C T c.395G>A p.R132H Missense 4 rs121913500 Acute Myeloid Leukemia Newly diagnosed AML who are greater than or equal to 75 years of age and who have comorbidities that preclude the use of intensive induction chemotherapy. Relapsed or refractory AML. Acute Myeloid Leukemia AML Ivosidenib IDH1 inhibition Targeted therapy 1 FDA-Approved "The U.S. Food and Drug Administration (FDA) granted approval to ivosidenib, an isocitrate dehydrogenase-1 (IDH1) inhibitor, indicated for the treatment of adult patients with a susceptible IDH1 mutation as detected by an FDA approved test with newly-diagnosed AML who are greater than or equal to 75 years old or who have comorbidities that preclude the use of intensive induction chemotherapy as well as relapsed or refractory AML." FDA "Servier Pharmaceuticals LLC. Tibsovo (ivosidenib) [package insert]. U.S. Food and Drug Administration website. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/211192_s008lbl.pdf. Revised August 2021. Accessed September 2nd, 2021." https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/211192_s008lbl.pdf 9/2/21 +IDH1 2 209113113 209113113 G A c.394C>T p.R132C Missense 4 rs121913499 Acute Myeloid Leukemia Newly diagnosed AML who are greater than or equal to 75 years of age and who have comorbidities that preclude the use of intensive induction chemotherapy. Relapsed or refractory AML. Acute Myeloid Leukemia AML Ivosidenib IDH1 inhibition Targeted therapy 1 FDA-Approved "The U.S. Food and Drug Administration (FDA) granted approval to ivosidenib, an isocitrate dehydrogenase-1 (IDH1) inhibitor, indicated for the treatment of adult patients with a susceptible IDH1 mutation as detected by an FDA approved test with newly-diagnosed AML who are greater than or equal to 75 years old or who have comorbidities that preclude the use of intensive induction chemotherapy as well as relapsed or refractory AML." FDA "Servier Pharmaceuticals LLC. Tibsovo (ivosidenib) [package insert]. U.S. Food and Drug Administration website. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/211192_s008lbl.pdf. Revised August 2021. Accessed September 2nd, 2021." https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/211192_s008lbl.pdf 9/2/21 +IDH1 2 209113112 209113112 C T c.395G>A p.R132H Missense 4 rs121913500 Cholangiocarcinoma Locally advanced or metastatic Cholangiocarcinoma CHOL Ivosidenib IDH1 inhibition Targeted therapy 1 FDA-Approved "The U.S. Food and Drug Administration (FDA) granted approval to ivosidenib, an isocitrate dehydrogenase-1 (IDH1) inhibitor, indicated for the treatment of adult patients with a susceptible IDH1 mutation as detected by an FDA approved test with locally advanced or metastatic cholangiocarcinoma who have been previously treated." FDA "Servier Pharmaceuticals LLC. Tibsovo (ivosidenib) [package insert]. U.S. Food and Drug Administration website. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/211192_s008lbl.pdf. Revised August 2021. Accessed September 2nd, 2021." https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/211192_s008lbl.pdf 9/2/21 +IDH1 2 209113113 209113113 G A c.394C>T p.R132C Missense 4 rs121913499 Cholangiocarcinoma Locally advanced or metastatic Cholangiocarcinoma CHOL Ivosidenib IDH1 inhibition Targeted therapy 1 FDA-Approved "The U.S. Food and Drug Administration (FDA) granted approval to ivosidenib, an isocitrate dehydrogenase-1 (IDH1) inhibitor, indicated for the treatment of adult patients with a susceptible IDH1 mutation as detected by an FDA approved test with locally advanced or metastatic cholangiocarcinoma who have been previously treated." FDA "Servier Pharmaceuticals LLC. Tibsovo (ivosidenib) [package insert]. U.S. Food and Drug Administration website. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/211192_s008lbl.pdf. Revised August 2021. Accessed September 2nd, 2021." https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/211192_s008lbl.pdf 9/2/21 +IDH1 Acute Myeloid Leukemia Newly diagnosed AML who are greater than or equal to 75 years of age and who have comorbidities that preclude the use of intensive induction chemotherapy. Relapsed or refractory AML. Acute Myeloid Leukemia AML Ivosidenib IDH1 inhibition Targeted therapy 1 FDA-Approved "The U.S. Food and Drug Administration (FDA) granted approval to ivosidenib, an isocitrate dehydrogenase-1 (IDH1) inhibitor, indicated for the treatment of adult patients with a susceptible IDH1 mutation as detected by an FDA approved test with newly-diagnosed AML who are greater than or equal to 75 years old or who have comorbidities that preclude the use of intensive induction chemotherapy as well as relapsed or refractory AML." FDA "Servier Pharmaceuticals LLC. Tibsovo (ivosidenib) [package insert]. U.S. Food and Drug Administration website. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/211192_s008lbl.pdf. Revised August 2021. Accessed September 2nd, 2021." https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/211192_s008lbl.pdf 9/2/21 +IDH1 Cholangiocarcinoma Locally advanced or metastatic Cholangiocarcinoma CHOL Ivosidenib IDH1 inhibition Targeted therapy 1 FDA-Approved "The U.S. Food and Drug Administration (FDA) granted approval to ivosidenib, an isocitrate dehydrogenase-1 (IDH1) inhibitor, indicated for the treatment of adult patients with a susceptible IDH1 mutation as detected by an FDA approved test with locally advanced or metastatic cholangiocarcinoma who have been previously treated." FDA "Servier Pharmaceuticals LLC. Tibsovo (ivosidenib) [package insert]. U.S. Food and Drug Administration website. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/211192_s008lbl.pdf. Revised August 2021. Accessed September 2nd, 2021." https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/211192_s008lbl.pdf 9/2/21 IDH2 15 90631934 90631934 C T c.419G>A p.R140Q Missense 4 rs121913502 Acute Myeloid Leukemia Relapsed or refractory Acute Myeloid Leukemia AML Enasidenib IDH2 inhibition Targeted therapy 1 FDA-Approved The U.S. Food and Drug Administration (FDA) granted regular approval to enasidenib for the treatment of adult patients with relapsed or refractory acute myeloid leukemia with an isocitrate dehydrogenase-2 (IDH2) mutation as detected by an FDA-approved test. FDA "Celgene Corporation. Idhifa (enasidenib) [package insert]. U.S. Food and Drug Administration website. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/209606s002lbl.pdf. Revised September 2019. Accessed November 12, 2020." https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/209606s002lbl.pdf NCT01915498 11/12/20 IDH2 15 90631837 90631837 C A c.516G>T p.R172S Missense 4 Acute Myeloid Leukemia Relapsed or refractory Acute Myeloid Leukemia AML Enasidenib IDH2 inhibition Targeted therapy 1 FDA-Approved The U.S. Food and Drug Administration (FDA) granted regular approval to enasidenib for the treatment of adult patients with relapsed or refractory acute myeloid leukemia with an isocitrate dehydrogenase-2 (IDH2) mutation as detected by an FDA-approved test. FDA "Celgene Corporation. Idhifa (enasidenib) [package insert]. U.S. Food and Drug Administration website. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/209606s002lbl.pdf. Revised September 2019. Accessed November 12, 2020." https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/209606s002lbl.pdf NCT01915498 11/12/20 IDH2 15 90631837 90631837 C T c.515G>A p.R172K Missense 4 Acute Myeloid Leukemia Relapsed or refractory Acute Myeloid Leukemia AML Enasidenib IDH2 inhibition Targeted therapy 1 FDA-Approved The U.S. Food and Drug Administration (FDA) granted regular approval to enasidenib for the treatment of adult patients with relapsed or refractory acute myeloid leukemia with an isocitrate dehydrogenase-2 (IDH2) mutation as detected by an FDA-approved test. FDA "Celgene Corporation. Idhifa (enasidenib) [package insert]. U.S. Food and Drug Administration website. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/209606s002lbl.pdf. Revised September 2019. Accessed November 12, 2020." https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/209606s002lbl.pdf NCT01915498 11/12/20 @@ -295,6 +301,10 @@ KIT 4 Melanoma Melanoma MEL Imatinib KIT inhibition Targeted therapy 1 KIT 4 11 Gastrointestinal Stromal Tumor Gastrointestinal Stromal Tumor GIST Imatinib KIT inhibition Targeted therapy 1 Guideline Approximately 90% of patients have diseases that respond to imatinib when their tumors have a KIT exon 11 mutation. Guideline "National Comprehensive Cancer Network. Gastrointestinal Stromal Tumors (GIST) NCCN Evidence Blocks (Version 2.2019). https://www.nccn.org/professionals/physician_gls/pdf/melanoma_blocks.pdf. Accessed August 10th, 2019." https://www.nccn.org/professionals/physician_gls/pdf/sarcoma_blocks.pdf 8/10/19 KIT 4 9 Gastrointestinal Stromal Tumor Gastrointestinal Stromal Tumor GIST Imatinib KIT inhibition Targeted therapy 1 Guideline "Approximately 50% of patients have diseases that respond to imatinib when their tumors have a KIT exon 9 mutation, and the likelihood of response improves with use of 800 mg dosage rather than the standard 400 mg." Guideline "National Comprehensive Cancer Network. Gastrointestinal Stromal Tumors (GIST) NCCN Evidence Blocks (Version 2.2019). https://www.nccn.org/professionals/physician_gls/pdf/melanoma_blocks.pdf. Accessed August 10th, 2019." https://www.nccn.org/professionals/physician_gls/pdf/sarcoma_blocks.pdf 8/10/19 KIT 4 Thymic carcinomas Thymic Carcinoma THYC Sunitinib KIT inhibition Targeted therapy 1 Guideline Sunitinib is recommended for patients with c-KIT mutations. Guideline "National Comprehensive Cancer Network. Thymomas and Thymic Carcinomas NCCN Evidence Blocks (Version 1.2021). https://www.nccn.org/professionals/physician_gls/pdf/thymic_blocks.pdf. Accessed November 19th, 2020." https://www.nccn.org/professionals/physician_gls/pdf/thymic_blocks.pdf 11/16/20 +KIT 4 55599321 55599321 A T c.2447A>T p.D816V Missense 17 Gastrointestinal Stromal Tumor Gastrointestinal Stromal Tumor GIST Avapritinib KIT inhibition Targeted therapy 1 Preclinical Avapritnib inhibited the autophosphorylation of KIT p.D816V in cellular assays relative to wild-type KIT. FDA "Blueprint Medicines Corporation. Ayvakit (avapritinib) [package insert]. U.S. Food and Drug Administration website. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/212608s007lbl.pdf. Accessed September 2nd, 2021." https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/212608s007lbl.pdf 9/2/21 +KIT 4 17 Gastrointestinal Stromal Tumor Gastrointestinal Stromal Tumor GIST Avapritinib KIT inhibition Targeted therapy 1 Preclinical Avapritnib inhibited the the profileration of KIT mutant cell lines. Avapritnib also had anti-tumor activity in mice implanted with an imatinib-resistant patient-derived xenograft model of human GIST with an activating KIT exon 11 or 17 variant. FDA "Blueprint Medicines Corporation. Ayvakit (avapritinib) [package insert]. U.S. Food and Drug Administration website. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/212608s007lbl.pdf. Accessed September 2nd, 2021." https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/212608s007lbl.pdf 9/2/21 +KIT 4 Mast Cell Leukemia Mast Cell Leukemia SMMCL Avapritinib KIT inhibition Targeted therapy 1 Preclinical Avapritnib inhibited the the profileration of KIT mutant cell lines. FDA "Blueprint Medicines Corporation. Ayvakit (avapritinib) [package insert]. U.S. Food and Drug Administration website. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/212608s007lbl.pdf. Accessed September 2nd, 2021." https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/212608s007lbl.pdf 9/2/21 +KIT 4 11 Gastrointestinal Stromal Tumor Gastrointestinal Stromal Tumor GIST Avapritinib KIT inhibition Targeted therapy 1 Preclinical Avapritnib had anti-tumor activity in mice implanted with an imatinib-resistant patient-derived xenograft model of human GIST with an activating KIT exon 11 or 17 variant. FDA "Blueprint Medicines Corporation. Ayvakit (avapritinib) [package insert]. U.S. Food and Drug Administration website. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/212608s007lbl.pdf. Accessed September 2nd, 2021." https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/212608s007lbl.pdf 9/2/21 KRAS 12 Lung Cancer Non-Small Cell Lung Cancer NSCLC Palbociclib + Trametinib CDK4/6 inhibition + MEK inhibition Targeted therapy 1 Preclinical "The combination of palbociclib and trametinib has shown antitumor and radiosensitizing activity in preclinical models of non-small cell lung cancer, and is currently in a phase III clinical trial for non-small cell lung cancer." Journal "Tao Z, Le blanc JM, Wang C, et al. Coadministration of Trametinib and Palbociclib Radiosensitizes KRAS-Mutant Non-Small Cell Lung Cancers In Vitro and In Vivo. Clin Cancer Res. 2016;22(1):122-33." https://doi.org/10.1158/1078-0432.CCR-15-0589 10.1158/1078-0432.CCR-15-0589 26728409 NCT02154490 9/14/18 KRAS 12 Ovarian Cancer "Ovarian Cancer, Other" OOVC Buparlisib + Trametinib PI3K/AKT/mTOR inhibition + MEK inhibition Targeted therapy 1 Clinical trial A phase 1b trial including 21 ovarian cancer patients demonstrated increased survival and an average PFS of 7 months when treated with a combination of buparlisib and trametinib (RP2D of buparlisib 60mg and trametinib 1.5mg daily). Journal "Bedard PL, Tabernero J, Janku F, et al. A phase Ib dose-escalation study of the oral pan-PI3K inhibitor buparlisib (BKM120) in combination with the oral MEK1/2 inhibitor trametinib (GSK1120212) in patients with selected advanced solid tumors. Clin Cancer Res. 2015;21(4):730-8." https://doi.org/10.1158/1078-0432.CCR-14-1814 10.1158/1078-0432.CCR-14-1814 25500057 NCT01155453 1/29/19 KRAS 12 2 Colorectal Cancer Primary or Metastatic Colorectal Adenocarcinoma COADREAD Cetuximab EGFR inhibition Targeted therapy 1 Guideline "Patients with primary or metastatic colorectal cancer and known KRAS mutations (exon 2, 3, and 4) should not be treated with either cetuximab or panitumumab. NCCN Guidelines colorectal cancer COL-B 4 of 5. " Guideline "National Comprehensive Cancer Network. Colon Cancer NCCN Evidence Blocks (Version 4.2018). https://www.nccn.org/professionals/physician_gls/pdf/colon_blocks.pdf. Accessed March 20th, 2019." https://www.nccn.org/professionals/physician_gls/pdf/colon_blocks.pdf 6/13/19 @@ -376,7 +386,10 @@ PALB2 Pancreatic Cancer Pancreatic Adenocarcinoma PAAD Platinum Plati PALB2 Prostate Cancer Metastatic castration resistant prostate cancer Prostate Adenocarcinoma PRAD Olaparib PARP inhibition Targeted therapy 1 FDA-Approved "The U.S. Food and Drug Administration (FDA) granted approval to olaparib for adult patients with deleterious or suspected deleterous germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC), who have progressed following prior treatment with enzalutamide or abiraterone." FDA "AstraZeneca Pharmaceuticals, LP. Lynparza (olaparib) [package insert]. U.S. Food and Drug Administration website. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/208558s014lbl.pdf. Revised May 2020. Accessed 22 October, 2020." https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/208558s014lbl.pdf 10/22/20 PBRM1 Nonsense Renal clear cell carcinoma Metastatic Renal Clear Cell Carcinoma CCRCC Nivolumab PD-1/PD-L1 inhibition Immunotherapy 1 Clinical evidence Clinical benefit from nivolumab in clear cell renal cell carcinoma patients was associated with loss-of-function mutations in PBRM1 Journal "Miao D, Margolis CA, Gao W, et al. Genomic correlates of response to immune checkpoint therapies in clear cell renal cell carcinoma. Science. 2018;359(6377):801-806." https://doi.org/10.1126/science.aan5951 10.1126/science.aan5951 29301960 9/11/18 PDGFRA 4 Gastrointestinal Stromal Tumor Gastrointestinal Stromal Tumor GIST Imatinib PDGF-R inhibition Targeted therapy 1 Guideline "Mutations in PDGFRA are associated with response to imatinib, with the exception of p.D842V." Guideline "National Comprehensive Cancer Network. Gastrointestinal Stromal Tumors (GIST) NCCN Evidence Blocks (Version 2.2019). https://www.nccn.org/professionals/physician_gls/pdf/melanoma_blocks.pdf. Accessed August 10th, 2019." https://www.nccn.org/professionals/physician_gls/pdf/sarcoma_blocks.pdf 8/10/19 -PDGFRA 4 55152093 55152093 A T c.2525A>T p.D842V Missense 18 rs121908585 Gastrointestinal Stromal Tumor Gastrointestinal Stromal Tumor GIST Imatinib PDGF-R inhibition Targeted therapy 1 Guideline "Mutations in PDGFRA are associated with response to imatinib, with the exception of p.D842V." Guideline "National Comprehensive Cancer Network. Gastrointestinal Stromal Tumors (GIST) NCCN Evidence Blocks (Version 2.2019). https://www.nccn.org/professionals/physician_gls/pdf/melanoma_blocks.pdf. Accessed August 10th, 2019." https://www.nccn.org/professionals/physician_gls/pdf/sarcoma_blocks.pdf 8/10/19 +PDGFRA 4 55152093 55152093 A T c.2525A>T p.D842V Missense 18 rs121908585 Gastrointestinal Stromal Tumor Gastrointestinal Stromal Tumor GIST Imatinib PDGF-R inhibition Targeted therapy 0 Guideline "Mutations in PDGFRA are associated with response to imatinib, with the exception of p.D842V." Guideline "National Comprehensive Cancer Network. Gastrointestinal Stromal Tumors (GIST) NCCN Evidence Blocks (Version 2.2019). https://www.nccn.org/professionals/physician_gls/pdf/melanoma_blocks.pdf. Accessed August 10th, 2019." https://www.nccn.org/professionals/physician_gls/pdf/sarcoma_blocks.pdf 8/10/19 +PDGFRA 4 55152093 55152093 A T c.2525A>T p.D842V Missense 18 rs121908585 Gastrointestinal Stromal Tumor Gastrointestinal Stromal Tumor GIST Avapritinib KIT inhibition Targeted therapy 1 Preclinical Avapritnib inhibited the autophosphorylation of PDGFRA p.D842V in cellular assays. FDA "Blueprint Medicines Corporation. Ayvakit (avapritinib) [package insert]. U.S. Food and Drug Administration website. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/212608s007lbl.pdf. Accessed September 2nd, 2021." https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/212608s007lbl.pdf 9/2/21 +PDGFRA 4 18 Gastrointestinal Stromal Tumor Unresctable or metastatic Gastrointestinal Stromal Tumor GIST Avapritinib KIT inhibition Targeted therapy 1 FDA-Approved "The U.S. Food and Drug Administration (FDA) granted approval to avapritinib, a KIT inhibitor, for the treatment of adults with unresectable or metastatic GIST harboring a platelet-derived growth factor alpha (PDGFRA) exon 18 variant, including PDGFRA p.D842V. " FDA "Blueprint Medicines Corporation. Ayvakit (avapritinib) [package insert]. U.S. Food and Drug Administration website. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/212608s007lbl.pdf. Accessed September 2nd, 2021." https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/212608s007lbl.pdf 9/2/21 +PDGFRA 4 55152093 55152093 A T c.2525A>T p.D842V Missense 18 rs121908585 Gastrointestinal Stromal Tumor Unresctable or metastatic Gastrointestinal Stromal Tumor GIST Avapritinib KIT inhibition Targeted therapy 1 FDA-Approved "The U.S. Food and Drug Administration (FDA) granted approval to avapritinib, a KIT inhibitor, for the treatment of adults with unresectable or metastatic GIST harboring a platelet-derived growth factor alpha (PDGFRA) exon 18 variant, including PDGFRA p.D842V. " FDA "Blueprint Medicines Corporation. Ayvakit (avapritinib) [package insert]. U.S. Food and Drug Administration website. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/212608s007lbl.pdf. Accessed September 2nd, 2021." https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/212608s007lbl.pdf 9/2/21 PBRM1 Frameshift Renal clear cell carcinoma Metastatic Renal Clear Cell Carcinoma CCRCC Nivolumab PD-1/PD-L1 inhibition Immunotherapy 1 Clinical evidence Clinical benefit from nivolumab in clear cell renal cell carcinoma patients was associated with loss-of-function mutations in PBRM1 Journal "Miao D, Margolis CA, Gao W, et al. Genomic correlates of response to immune checkpoint therapies in clear cell renal cell carcinoma. Science. 2018;359(6377):801-806." https://doi.org/10.1126/science.aan5951 10.1126/science.aan5951 29301960 9/11/18 PIK3CA Breast Cancer Advanced or metastatic Invasive Breast Carcinoma BRCA Alpelisib PI3K/AKT/mTOR inhibition Targeted therapy 1 FDA-Approved "Alpelisib is a kinase inhibitor indictated in combination with fulvestrant for the treatment of postmenopausal women, and men, with HR+, HER2-negative, PIK3CA mutated, advanced or metastatic breast cancer as detected by an FDA-approved test following progression on or after an endrocrine-based regime. " FDA "Novartis Pharmaceuticals Corporation. Piqray (alpelisib) [package insert]. U.S. Food and Drug Administration website. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212526s001lbl.pdf. Revised September 2020. Accessed November 12, 2020." https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212526s001lbl.pdf 11/12/20 PIK3CA 3 Breast Cancer Breast Invasive Ductal Carcinoma IDC Pictilisib PI3K/AKT/mTOR inhibition Targeted therapy 1 Preclinical "PIK3CA, but not AKT1 mutation, increased sensitivity to the PI3K inhibitor GDC-0941 and the allosteric AKT inhibitor MK-2206" Journal "Beaver JA, Gustin JP, Yi KH, et al. PIK3CA and AKT1 mutations have distinct effects on sensitivity to targeted pathway inhibitors in an isogenic luminal breast cancer model system. Clin Cancer Res. 2013;19(19):5413-22." https://doi.org/10.1158/1078-0432.CCR-13-0884 10.1158/1078-0432.CCR-13-0884 23888070 6/13/19 diff --git a/docs/content-changelog.md b/docs/content-changelog.md index b675f7d..5c08bbb 100644 --- a/docs/content-changelog.md +++ b/docs/content-changelog.md @@ -1,6 +1,20 @@ # Content Changelog The following changes have been made to the content catalogued within the Molecular Oncology Almanac knowledge base. +## September 2021 release +Added entries: +- (FDA) _IDH1_ p.R132C, p.R132H and sensitivity to ivosidenib in acute myeloid leukemia and cholangiocarcinoma. +- (FDA) _IDH1_ somatic variants and sensitivity to ivosidenib in acute myeloid leukemia and cholangiocarcinoma. +- (FDA) _PDGFRA_ p.D842V and sensitivity to avapritinib in gastrointestinal stromal tumors. +- (Preclinical) _KIT_ p.D816V and sensitivity to avapritinib in gastrointestinal stromal tumors. +- (Preclinical) _KIT_ exon 11 and 17 somatic variants and sensitivity to avapritinib in gastrointestinal stromal tumors. +- (Preclinical) _KIT_ somatic variants and sensitivity to avapritinib in mast cell leukemia. +- (Preclinical) _PDGFRA_ p.D842V and sensitivity to avapritinib in gastrointestinal stromal tumors. +- (Preclinical) _PDGFRA_ exon 18 somatic variants and sensitivity to avapritinib in gastrointestinal stromal tumors + +Revised entries: +- (Guideline) _PDGFRA_ p.842V and sensitivity to imatinib was revised to not sensitive. + ## June 2021 release Added entries: - (FDA) _EGFR_ exon 20 insertion somatic variants and sensitivity to amivantamab-vmjw in metastatic non-small cell lung cancer. @@ -12,7 +26,7 @@ Added entries: - (FDA) _ERBB2_ amplifications and sensitivity to pembrolizumab in combination with fluoropyrimidine, trastuzumab, and platinum-based chemotherapy in gastric or gastroesophageal junction adenocarcinoma. - (Inferential) _CD274_ amplifications and sensitivity to pembrolizumab in gastric or gastroesophageal junction adenocarcinoma. -Edited entries: +Revised entries: - (Clinical evidence) _NF1_ germline variants associated with radiation therapy was not labeled with a clinical assertion. "1" has been set for adverse_event_risk. - (Inferential) _ERBB2_ amplification and sensitivity to trastuzumab was changed to an inferential assertion from FDA. The description was also updated for these entries. @@ -24,7 +38,7 @@ Added entries: - (FDA) _EGFR_ exon 19 deletions and sensitivity to osimertinib in non-small cell lung cancer. - (FDA) HER2-positive breast cancer and sensitivity to margetuximab-cmkb + chemotherapy. -Edited entries: +Revised entries: - (Guideline) _ABL1_ p.T315I suggesting sensitivity to Omacetaxine in CML has been recategorized from a targeted therapy to chemotherapy. - (Guideline) MSI-High associated with resistance to 5-Fluorouracil in colorectal adenocarcinoma. 5-Fluorouracil was reclassified as a chemotherapy therapy type instead of targeted therapy. - (Guideline) _TET2_ somatic variants suggesting sensitivity to azacitidine was changed from a targeted therapy to chemotherapy. @@ -44,7 +58,7 @@ Added entries: - (FDA) _RET_ fusions associated with sensitivity to pralsetinib in advanced or metastatic thyroid cancer. - (Inferential) _CDK274_ amplifications associated with sensitivity to chemotherapy in combination with pembrolizumab in locally recurrent or metastatic triple-negative breast cancer. -Edited entries: +Revised entries: - (Guideline) _CDK4_ amplifications associated with sensitivity to palbociclib in well-differentiated and dedifferentiated liposarcoma, updated source. - (Guideline) _KIT_ somatic variants associated with sensitivity to sunitinib in thymic carcinomas, updated source. @@ -81,5 +95,5 @@ Added entries: - (FDA) _RET_ fusions associated with sensitivity to selpercatinib in non-small cell lung cancer and thyroid cancer. - (Inferential) COSMIC Signature 3, associated with Homologous Recombination Deficiency (HRD), associated with sensitivity to bevacizumab and olaparib in advanced ovarian, fallopian tube, and peritoneal cancer. -Edited entries: +Revised entries: - (Clinical trial) _ATM_ frameshift, nonsense, and splice site somatic variants associated with sensitivity to BAY1895344 in any solid tumor. Updated disease context from "Advanced metastatic" to "Advanced or metastatic". diff --git a/docs/template-content-changelog.md b/docs/template-content-changelog.md index bbbc860..fb17c09 100644 --- a/docs/template-content-changelog.md +++ b/docs/template-content-changelog.md @@ -7,7 +7,7 @@ Use the following template for monthly entries in the content changelog. You can Added entries: - ({Evidence level of source}) {molecular feature(s)} {assertion} in {disease context} {ontology}. -Edited entries: +Revised entries: - ({Evidence level of source}) {molecular feature(s)} {assertion} in {disease context} {ontology}. {description of change}. Removed entries: