LBA32 - Encorafenib plus Cetuximab With or Without Binimetinib for BRAF V600E–Mutant Metastatic Colorectal Cancer: Expanded Results from a Randomized, 3-Arm, Phase III Study vs. the Choice of Either Irinotecan or FOLFIRI plus Cetuximab (BEACON CRC)

Background

Encorafenib (ENCO) + binimetinib (BINI) + cetuximab (CETUX) significantly improved overall survival (OS, HR:0.52, P < 0.0001) and objective response rates (ORR, 26% vs 2%, P < 0.0001) in patients (pts) with BRAFV600E metastatic colorectal cancer (mCRC) compared with current standard of care. This analysis focuses on the triplet ((ENCO+CETUX+BINI) and doublet (ENCO+CETUX) arms.

Methods

The BEACON CRC study was a randomized, 3-arm, phase 3 study which evaluated triplet or doublet vs. investigator’s choice of irinotecan or FOLFIRI + CETUX in 665 pts with BRAFV600E mCRC. The triplet vs doublet efficacy comparison was a secondary endpoint (not formally powered). Analyses included efficacy (OS, ORR, depth of response, and progression-free survival [PFS]), multivariate modeling, safety, and quality of life (QOL) assessments (EORTC QOL Questionnaire (QLQ C30), Functional Assessment of Cancer Therapy Colon Cancer, EuroQol 5D 5L, and Patient Global Impression of Change).

Results

224 and 220 pts were randomized to triplet and doublet, respectively. Median overall survival for triplet and doublet was 9.0 (95%CI: 8.0, 11.4) and 8.4 months (95%CI: 7.5, 11.0), respectively (HR:0.79 [95%CI: 0.59, 1.06]). ORR was 26% (95%CI: 18%, 35%) for triplet and 20% (95%CI: 13%,29%) for doublet. For pts with 1 prior therapy, ORR was 34% (95%CI: 23, 47) for triplet and 22% (95%CI: 14, 33) for doublet. Waterfall plots indicated that depth of response favored triplet. Grade 3+ adverse events (AE) were 58% in triplet and 50% in doublet. Rates of discontinuation due to an AE were similar (triplet: 7%; doublet: 8%), with median relative dose intensity maintained for both arms. There were no differences in QOL across 4 instruments. Some toxicities occurred less frequently with the triplet.

Conclusions

In BEACON CRC, triplet and doublet showed encouraging activity in BRAFV600E mCRC. Data suggest that the triplet offers improved efficacy vs doublet with some additional manageable toxicity and no impact on overall QOL. Further follow-up will better define the relative benefits of the regimens.

Clinical trial identification

NCT02928224.

Editorial acknowledgement

Editorial assistance was provided by JD Cox and Mayville Medical Communications, with funding from Array Biopharma.

Legal entity responsible for the study

Array BioPharma Inc.

Funding

Array BioPharma Inc.

Disclosure

J. Tabernero: Advisory / Consultancy: Bayer; Advisory / Consultancy: Boehringer; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: MSD; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Novartis; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Taiho; Advisory / Consultancy: Merrimack; Advisory / Consultancy: Peptomyc; Advisory / Consultancy: Rafael Pharmaceuticals; Advisory / Consultancy: Symphogen; Advisory / Consultancy: Chugai Pharma; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Merus; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Seattle Genetics; Advisory / Consultancy: Array BioPharma; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: BeiGene. A. Grothey: Honoraria (self): Elsevier; Honoraria (self): Aptitude Health; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Genentech; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Eli Lilly; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Boston Biomedical; Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Advisory / Consultancy, Research grant / Funding (institution): Array BioPharma; Advisory / Consultancy: Guardant Health; Advisory / Consultancy, Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Eisai; Travel / Accommodation / Expenses: MSD; Travel / Accommodation / Expenses: Boehringer Ingelheim. E. Van Cutsem: Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): Eli Lilly; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Servier; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Celgene; Advisory / Consultancy: MSD; Advisory / Consultancy, Research grant / Funding (institution): Merck KGaA; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: AstraZeneca; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Ipsen; Research grant / Funding (institution): Merck. R. Yaeger: Research grant / Funding (institution), Travel / Accommodation / Expenses: Array BioPharma; Research grant / Funding (institution): GSK; Research grant / Funding (institution): Novartis; Speaker Bureau / Expert testimony: Sysmex; Research grant / Funding (institution): Symphogen; Licensing / Royalties: Biocartis. H. Wasan: Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution): Merck KGaA; Honoraria (self), Speaker Bureau / Expert testimony: Celgene; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Sirtex Medical; Honoraria (self): Array BioPharma; Honoraria (self), Advisory / Consultancy: Shire; Honoraria (self): Genentech; Honoraria (self), Advisory / Consultancy: ERYTECH Pharma; Advisory / Consultancy: Roche; Advisory / Consultancy: Incyte; Speaker Bureau / Expert testimony: Servier; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): MSD. T. Yoshino: Research grant / Funding (institution): Chugai Pharma; Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Sumitomo Dainppon; Research grant / Funding (institution): GSK. J. Desai: Advisory / Consultancy, Research grant / Funding (institution): Eli Lilly; Advisory / Consultancy, Research grant / Funding (institution): Bionomics; Advisory / Consultancy: Eisai; Advisory / Consultancy, Research grant / Funding (institution): BeiGene; Advisory / Consultancy: Ignyta; Research grant / Funding (institution): Roche; Research grant / Funding (institution): GSK; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Ipsen. F. Ciardiello: Advisory / Consultancy, Research grant / Funding (institution): Genentech; Advisory / Consultancy, Research grant / Funding (institution): Merck KGaA; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): Amgen; Advisory / Consultancy: Pfizer; Research grant / Funding (institution): Servier; Research grant / Funding (institution): Symphogen; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Ipsen. N. Steeghs: Research grant / Funding (institution): AstraZeneca/MedImmune; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): GSK; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Blueprint Medicines; Research grant / Funding (institution): AB Science; Research grant / Funding (institution): Deciphera; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Merus; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Incyte. H. Arkenau: Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): GSK; Research grant / Funding (institution): Servier; Research grant / Funding (institution): Astellas; Research grant / Funding (institution): Array BioPharma; Research grant / Funding (institution), Travel / Accommodation / Expenses: Iovance; Full / Part-time employment: SCRI. A. Gollerkeri: Full / Part-time employment: Pfizer Inc.. M. Pickard: Full / Part-time employment: Pfizer Inc.. K. Maharry: Full / Part-time employment: Pfizer Inc.. J.L. Christy-Bittel: Full / Part-time employment: Pfizer Inc.. L. Anderson: Full / Part-time employment: Pfizer Inc.. S. Kopetz: Shareholder / Stockholder / Stock options: MolecularMatch; Research grant / Funding (institution), Shareholder / Stockholder / Stock options: Navire ; Advisory / Consultancy: Roche; Advisory / Consultancy, Research grant / Funding (institution): Genentech; Advisory / Consultancy, Research grant / Funding (institution): EMD Serono; Advisory / Consultancy: Merck; Advisory / Consultancy: Karyopharm; Advisory / Consultancy: Amal Therapeutics; Advisory / Consultancy: Symphogen; Advisory / Consultancy: Holy Stone; Advisory / Consultancy, Research grant / Funding (institution): Biocartis; Advisory / Consultancy, Research grant / Funding (institution): Amgen; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Boehringer Ingelheim; Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Guardian Health; Research grant / Funding (institution): Array BioPharma; Research grant / Funding (institution): MedImmune. All other authors have declared no conflicts of interest.