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Evaluating age as a factor for survival and quality of life in patients with BRAF V600E-mutant metastatic colorectal cancer treated with encorafenib + cetuximab ± binimetinib: Subanalysis of BEACON CRC
Background
Although the majority of colorectal cancer (CRC) diagnoses occur in adults ≥50 years old (y), there has been a rise in CRC diagnoses in adults BRAF V600E-mutant metastatic CRC (mCRC). This subanalysis evaluates the effect of age on survival, QoL, and safety in patients from BEACON CRC.
Methods
BEACON CRC was a randomized, open-label, phase 3 study comparing enco+cetux±bini and investigator’s choice of irinotecan+cetux or FOLFIRI+cetux (control) in patients with previously treated BRAF V600E-mutant mCRC. PFS, OS, patient-reported QoL, and safety were assessed by age at enrollment (< 50 or ≥50 y). QoL was measured using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30) and Functional Assessment of Cancer Therapy-Colorectal (FACT-C). The Kaplan–Meier method was used to calculate median PFS and OS with 95% confidence intervals (CIs) for each subgroup. For OS, Cox proportional hazards models were used to estimate the hazard ratio (HR) with 95% CI.
Results
Patients in each treatment arm were stratified by age: < 50 y (enco+cetux+bini, n=47/224; enco+cetux, n=33/220; control, n=49/221) and ≥50 y (enco+cetux+bini, n=177/224; enco+cetux, n=187/220; control, n=172/221). Median (95% CI) PFS by age < 50 y and ≥50 y, respectively, for enco+cetux+bini was 5.0 (3.94–5.55) and 4.4 (4.17–5.55) months; for enco+cetux, 4.3 (2.92–6.01) and 4.3 (4.04–5.52) months; and for control, 1.5 (1.05–1.58) and 1.6 (1.48–2.20) months. Median OS (95% CI) by age < 50 y and ≥50 y, respectively, for enco+cetux+bini was 9.8 (7.56–12.48) and 9.0 (8.02–11.73) months; for enco+cetux, 10.3 (7.26–not reached) and 8.8 (7.89–11.24) months; and for control, 5.4 (3.75–8.90) and 6.4 (5.09–7.39) months. Within each treatment group, OS was similar between age groups: HR (95% CI) for enco+cetux+bini, 0.92 (0.60–1.40); enco+cetux, 0.63 (0.37–1.08); control, 1.24 (0.85–1.80). Mean changes from baseline in QLQ-C30 and FACT-C scores were similar within the same treatment group, regardless of age. Overall, the incidence and severity of adverse events (AEs) were similar within treatment groups, regardless of age; for enco+cetux, there were fewer grade 3/4 AEs in the < 50 y group (39.4%) than in the ≥50 y group (60.7%).
Conclusions
In this subanalysis of BEACON CRC, OS was similar between age groups for patients with BRAF V600E-mutant mCRC. Patients < 50 y had fewer grade 3/4 AEs in the enco+cetux group. This subanalysis is limited by the low number of patients. Further analyses are warranted to compare these age groups when treated with targeted therapies for mCRC.
Clinical trial identification
NCT02928224.
Editorial acknowledgement
Medical writing and editorial support were provided by Alexus Kolb, PhD, at Caudex.
Legal entity responsible for the study
Anjali Belani and Carolin Guenzel.
Funding
The BEACON trial was sponsored by Array BioPharma Inc., which was acquired by Pfizer in July 2019, and was conducted with support from Merck KGaA, Darmstadt, Germany (for sites outside of North America), ONO Pharmaceutical, and Pierre Fabre. This work was also supported by the Cancer Center Core Grant P30 CA 008748 to Memorial Sloan-Kettering Cancer Center.
Disclosures
K. Ng: Advisory / Consultancy: Seattle Genetics, Bicara Therapeutics, GlaxoSmithKline; Research grant / Funding (institution): Pharmavite, Evergrande Group, Janssen. E. Van Cutsem: Advisory / Consultancy: Abbvie, Array, Astellas, Astrazeneca, Bayer, Beigene, Biocartis, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Daiichi, Halozyme, GSK, Helsinn, Incyte, Ipsen, Janssen Research, Lilly, Merck Sharp & Dohme, Merck KGaA, Mirati, Novartis, Pierre Fabre, Roche, Seattle Genetics, Servier, Sirtex, Terumo, Taiho, TRIGR, Zymeworks; Research grant / Funding (institution): Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Novartis, Roche, Servier . R. Yaeger: Advisory / Consultancy: Mirati Therapeutics, Pfizer; Research grant / Funding (institution): Pfizer, Mirati Therapeutics, Boehringer Ingelheim. T. Yoshino: Honoraria (self): Taiho Pharmaceutical, Chugai Pharmaceutical, Eli Lilly, Merck Biopharma, Bayer Yakuhin, Ono Pharmaceutical and MSD; Research grant / Funding (institution): Ono Pharmaceutical, Sanofi, Daiichi Sankyo, PAREXEL International, Pfizer Japan, Taiho Pharmaceutical, MSD, Amgen, Genomedia, Sysmex, Chugai Pharmaceutical and Nippon Boehringer Ingelheim. J. Desai: Advisory / Consultancy: Bionomics, BeiGene, Eli Lilly, Ignyta (Inst), Eisai; Research grant / Funding (institution): Roche, Bionomics, Eli Lilly, GlaxoSmithKline, MedImmune, Bristol Myers Squibb, Novartis, BeiGene. H. Wasan: Honoraria (self): Servier, Incyte, Pierre Farbre; Advisory / Consultancy: Servier, Incyte, Pierre Farbre; Speaker Bureau / Expert testimony: Servier, Incyte, Pierre Farbre; Research grant / Funding (institution): Pfizer, Sirtex; Travel / Accommodation / Expenses: Servier, Incyte, Pierre Farbre. B. Alkuzweny: Full / Part-time employment: Pfizer. X. Zhang: Shareholder / Stockholder / Stock options: Pfizer; Full / Part-time employment: Pfizer; Spouse / Financial dependant: Pfizer. J. Tabernero: Honoraria (self): educational collaboration with Imedex, Medscape Education, MJH Life Sciences, PeerView Institute for Medical Education and Physicians Education Resource (PER).; Advisory / Consultancy: scientific consultancy role for Array Biopharma, AstraZeneca, Avvinity, Bayer, Boehringer Ingelheim, Chugai, Daiichi Sankyo, F. Hoffmann-La Roche Ltd, Genentech Inc, HalioDX SAS, Hutchison MediPharma International, Ikena Oncology, Inspirna Inc, IQVIA, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Ona Therapeutics, Orion Biotechnology, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Seattle Genetics, Scandion Oncology, Servier, Sotio Biotech, Taiho, Tessa Therapeutics and TheraMyc. S. Kopetz: Advisory / Consultancy: Roche, Redx Pharma, Jacobio, Merck, Navire Pharma, Holy Stone, Biocartis, Natera, Karyopharm Therapeutics, Repare Therapeutics, Genentech, Lilly, AstraZeneca/MedImmune, EMD Serono, Daiichi Sankyo, Amal Therapeutics, Boehringer Ingelheim, Bayer Health, Lutris, Pfizer, Amgen, Pierre Fabre, Symphogen, Novartis, Boston Biomedical, Ipsen, HalioDx, Inivata, GSK, Jazz pharmaceuticals Iylon, Xilis, Abbvie, Gilead Sciences, Mirati Therapeutics, Flame Biosciences, Servier, Carina Biotechnology, Bicara Therpeutics, Endeavor BioMedicines, Numab Pharma, Johnson & Johnson/Janssen, Genomic Health, Fro; Research grant / Funding (self): Sanofi, Biocartis, Guardant Health, Array BioPharma, Genentech/ Roche, EMD Serono, MedImmune, Novartis, Amgen, Lilly, Daiichi Sankyo; Shareholder / Stockholder / Stock options: MolecularMatch, Frontier Medicines, Lutris, Iylon. The author has declared no conflicts of interest.
