Abstract 91P
Background
BRAF V600E mutation in mCRC is a biomarker of poorer prognosis and is present in 10% of pts. To date, there are no 1L treatments targeted for BRAF V600E-mutant mCRC. This study described the real-world clinical outcomes of pts with BRAF V600E-mutant mCRC treated with 1L standard of care (SOC) regimens.
Methods
Adult pts with BRAF V600E-mutant mCRC who received 1L chemotherapy regimens (FOLFOX, FOLFIRI, CAPOX, FOLFOXIRI, with/without bevacizumab [± BEV]) were identified from Flatiron Health data (2013 – 2020). Pts with a record of mismatch repair deficient/microsatellite instability-high mCRC and an Eastern Cooperative Oncology Group Performance Status > 1 were excluded. The objective response rate (ORR) was calculated as the proportion of pts achieving complete or partial response on 1L therapy, with duration of response (DOR) estimated in this group using the Kaplan-Meier (KM) method. Progression-free survival (PFS) and overall survival (OS) were estimated using KM analyses. Sensitivity analyses were conducted to assess the robustness of DOR and PFS results to alternative censoring specifications. Analyses were conducted overall, and separately in pts receiving FOLFOX ± BEV and FOLFIRI ± BEV.
Results
Of 209 pts (mean [standard deviation] age: 64.4 [12.8] years; White: 72.2%), 127 (60.8%) received FOLFOX ± BEV and 49 (23.4%) received FOLFIRI ± BEV. Over a median follow up of 10.7 months, ORR was 45.0% (95% confidence interval [CI]: 38.2‒52.0) and median DOR was 6.5 months (5.7‒6.9). Median PFS and OS were 6.8 months (5.9‒7.9) and 14.3 months (12.2‒18.3). ORR and median DOR were 48.0% (39.1–57.0) and 6.2 months (4.2‒8.1) for FOLFOX ± BEV, and 44.9% (30.9–59.7) and 6.5 months (5.7–10.3) for FOLFIRI ± BEV. Median PFS and OS were 6.3 months (5.5‒7.9) and 12.7 months (11.4–19.6) for FOLFOX ± BEV, and 7.9 months (6.0‒9.7) and 17.2 months (12.2–26.8) for FOLFIRI ± BEV. Consistent results were observed across sensitivity analyses.
Conclusions
Response to 1L SOC regimens for BRAF V600E-mutant mCRC is still limited and pts treated with 1L SOC have poor survival outcomes. Our findings underscore an unmet need for novel, effective therapies that are targeted to this population.
Legal entity responsible for the study
The authors.
Funding
Pfizer, Inc.
Disclosure
A. Parikh: Financial Interests, Personal, Advisory Role: Lilly, Checkmate Pharmaceuticals, Biofidelity, Guardant Health, FMI, AbbVie, Value Analytics Labs, Bayer, Taiho Oncology, Delcath Systems, Seagen, CVS, SAGA Diagnostics, Scarce, Inc, Illumina, UpToDate, Takeda, Mirati, Pfizer, Inivata, Xilio Therapeutics, Sirtex, Science for America; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Karkinos Healthcare; Financial Interests, Institutional, Research Grant: Plexxikon, Bristol Myers Squibb, Genentech, Novartis Pharmaceuticals UK Ltd., PureTech, PMV Pharma, Mirati Therapeutics, Daiichi Sankyo, Erasca, Inc, Takeda, Syndax; Financial Interests, Personal, Stocks/Shares: C2i Genomics, XGenomes, Cadex, Vionix, Parithera; Financial Interests, Personal, Advisory Board: AZ, Hookipa, Kahar Medical; Financial Interests, Personal, Other, Steering Committee: Exilixis; Financial Interests, Personal, Other, DSMC: Roche. J. Tabernero: Financial Interests, Personal, Advisory Board, scientific consultancy role: Orion Biotechnology, AstraZeneca, Boehringer Ingelheim, Chugai, Daiichi Sankyo, F. Hoffmann-La Roche Ltd., Genentech Inc., Ikena Oncology, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Seattle Genetics, Servier, Taiho, Scandion Oncology, Ona Therapeutics, Sotio Biotech, Inspirna Inc, Scorpion Therapeutics, Tolremo Therapeutics, CARSgen Therapeutics, hC Bioscience Inc, Takeda Pharmaceuticals International AG, Alentis Therapeutics, Immodulon Therapeutics; Financial Interests, Personal, Invited Speaker, educational collaboration: Medscape Education, Physicians Education Resource (PER), PeerView Institute for Medical Education, Imedex/HMP; Financial Interests, Personal, Advisory Board: Cardiff Oncology, Aveo Oncology; Financial Interests, Personal, Stocks/Shares: Oniria Therapeutics, 1TRIALSP, Alentis Therapeutics, Pangaea Oncology; Financial Interests, Institutional, Research Grant, ACRCelerate: Colorectal Cancer Stratified: Fundación Científica de la Asociación Española Contra el Cáncer; Financial Interests, Institutional, Research Grant, OPTIMISTICC: Opportunity to Investigate the Microbiome’s Impact on Science and Treatment In Colorectal Cancer: Cancer Research UK; Financial Interests, Institutional, Funding, Clinical Trials & Research: Amgen Inc, AstraZeneca Pharmaceuticals LP, Bristol Myers Squibb International Corporation, Celgene International SARL, Debiopharm International SA, F. Hoffmann-La Roche Ltd., Genentech Inc, Janssen-Cilag International NV, Merck Health KGaA, Merck, Sharp & Dohme de España, SA, Novartis Farmacéutica SA, PharmaMar SA, Sanofi-Aventis Recherche & Développement, Servier, Taiho Pharma USA, Inc, BeiGene, Boehringer Ingelheim, Menarini, Merus N V, Pfizer, Mirati; Non-Financial Interests, Member of Board of Directors, Board of Directors: Cancer Core Europe, Spanish Association Against Cancer -AECC; Non-Financial Interests, Member of Board of Directors, General Assembly: Horizon Europe Cancer Mission; Non-Financial Interests, Leadership Role, External Scientific Committee: Institute for Health Research INCLIVA e Clinical Hospital of Valencia, IdiSNA eUniversidad de Navarra; Non-Financial Interests, Leadership Role, Scientific Advisory Board: Spanish National Cancer Research Centre (CNIO); Non-Financial Interests, Advisory Role, International Scientific Evaluation Committee: Bosch Health Campus (BHC); Non-Financial Interests, Advisory Role, Review Board: National Decade Against Cancer (NCT) - German Consortium for Translational Cancer Research (DKTK); Non-Financial Interests, Advisory Role, Scientific Advisory Board: Karolinska Comprehensive Cancer Centre; Non-Financial Interests, Advisory Role, International Review Committee (IRC): Oncode Institute; Non-Financial Interests, Advisory Role, Scientific Advisory Board (SAB): Oslo University Hospital Comprehensive Cancer Centre (OUH CCC); Non-Financial Interests, Leadership Role, Governance Advisory Committee: European Organization for Research and Treatment of Cancer -EORTC; Non-Financial Interests, Leadership Role, Vice Chairman: World Innovative Networking (WIN) Consortium in Personalized Cancer Medicine; Non-Financial Interests, Other, Coordinating PI & Steering Committee Member. Clinical Trials & Research: Array Biopharma Inc., AstraZeneca Pharmaceutical LP, Boehringer Ingelheim, MedImmune, Menarini, Merck Healthcare KGaA, Merck, Sharp & Dohme de España SA, Pfizer, Servier; Non-Financial Interests, Principal Investigator, Clinical Trials & Research: Array Biopharma Inc., AstraZeneca Pharmaceutics LP, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb International Corporation, Celgene International SARL, Debiopharm International SA, F. Hoffmann-La Roche Ltd., Genentech Inc., HalioDX SAS, Hutchinson Medipharma, Janssen-Cilag International NV, MedImmune, Menarini, Merck Healthcare KGaA, Merck, Sharp & Dohme de España SA, Merus NV, Mirati, Novartis Farmacéutica SA, Pfizer, Sanofi-Aventis Recherche & Développement, Servier, Taiho Pharma USA Inc; Non-Financial Interests, Other, Steering Committee Member. Clinical Trials & Research: Debiopharm International SA, F. Hoffmann-La Roche Ltd., Genentech Inc., HalioDX SAS, Hutchinson Medipharma, Janssen-Cilag International NV, Merus NV, Taiho Pharma USA Inc; Non-Financial Interests, Other, Coordinating PI. Clinical Trials & Research: Mirati; Non-Financial Interests, Member: AACR, ASCO, EACR, EORTC, SEOM; Other, President: Oncology Master Plan e Catalonia Department of Health; Other, Advisory Committee: Advisory Committee on Pharmaceutical Provision Financing under the Spanish National Health System. M.E. M.C. Vieira: Financial Interests, Personal, Full or part-time Employment: Pfizer, Inc.; Financial Interests, Personal, Stocks/Shares: Pfizer, Inc., Novartis. K. Kponee-Shovein, M. Cheng, J. Liu, H. Kang: Financial Interests, Institutional, Sponsor/Funding, I am an employee of Analysis Group, which received funding from Pfizer Inc. for conducting this study: Pfizer, Inc. B. Li, X. Zhang: Financial Interests, Personal, Full or part-time Employment: Pfizer Inc.; Financial Interests, Personal, Stocks/Shares: Pfizer Inc.