85MO - Management of adverse events associated with encorafenib plus cetuximab in patients with BRAF V600E mutant metastatic colorectal cancer (BEACON CRC Study)

Background

BRAF mutations occur in up to 15% of patients with metastatic colorectal cancer (mCRC),the BRAF V600E mutation is a marker of poor prognosis. In BEACON CRC study,triplet therapy encorafenib + binimetinib + cetuximab and doublet therapy with encorafenib + cetuximab demonstrated improved overall survival (OS) and objective response in patients with BRAF V600E mCRC compared with current standard of care (median OS: 9.3 months (m) [triplet] and 9.3 m [doublet] vs 5.9 m [control]; ORR:27% [triplet] 20% [doublet] vs 2% [control], p<0.0001 for both). Here, we focus on common adverse events (AEs) that occurred during the study with the doublet regimen, and best practices on managing and mitigating these events.

Methods

BEACON CRC is a randomized, 3-arm, Ph 3 study evaluating triplet (n=224) or doublet (n=220) regimens vs investigator’s choice of irinotecan or FOLFIRI + cetuximab (n=221) in patients (pts) with BRAF V600E-mutated mCRC. Incidence and severity of AEs were assessed according to the NCICTCAE, version 4.03.

Results

In the doublet arm, the most common any grade AEs were diarrhea (38%), nausea (38%), fatigue (33%), decreased appetite (31%). The most common skin-related any grade AEs were dermatitis acneiform (30%), rash (15%), dry skin (13%), pruritus (11%). Grade ≥3 AEs occurred in 57% of pts (vs 64% in the control arm) and the most common were anemia (6%), intestinal obstruction (5%), fatigue (4%), asthenia (4%), abdominal pain (3%). Common laboratory abnormalities included low hemoglobin (any grade: 39%, grade 3–4: 6%) and high creatinine (any grade: 54%, grade 3–4: 3%). Any grade arthralgia and myalgia, associated with BRAF inhibitors, occurred in 23% and 15% of pts, and led to dose reductions of either study drug in <1% of pts; no pts discontinued either drug. Discontinuation of any study drug primarily due to an AE occurred in 12% of patients (vs 17% in the control arm). Management of AEs with the doublet regimen and management of class-based AEs will be described.

Conclusions

AEs that occurred with encorafenib + cetuximab during the BEACON CRC study were generally manageable, reversible, and infrequently associated with treatment discontinuation.

Clinical trial identification

NCT02928224.

Editorial acknowledgement

Writing and editorial assistance were provided by Namiko Abe, PhD, of Caudex, funded by Pfizer.

Legal entity responsible for the study

Pfizer.

Funding

Pfizer.

Disclosure

C-F. Chiu: Research grant/Funding (institution): Array Biopharma; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): F. Hoffmann-La Roche Ltd; Research grant/Funding (institution): MSD; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Ono; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Janssen-Cilag SA. Y-M. Yeh: Research grant/Funding (institution): Pfizer. K-H. Yeh: Research grant/Funding (institution): Pfizer. J. Desai: Advisory/Consultancy: Eli Lilly; Eisai; BeiGene; Biocon; Amgen; Research grant/Funding (institution): Roche; GSK; Novartis; Bionomics; BeiGene; Eli Lilly; BMS; AstraZeneca; MedImmune. T.J. Price: Research grant/Funding (institution): Amgen; Advisory/Consultancy: MSD; Advisory/Consultancy: Amgen. N. Tebbutt: Honoraria (self), Advisory/Consultancy: Bayer; Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: Merck Serono. J. Tabernero: Honoraria (self), Advisory/Consultancy: Array Biopharma; AstraZeneca; Bayer; BeiGene; Roche Diagnostics; Boehringer Ingelheim; Chugai; F. Hoffmann-La Roche Ltd.; Merck Serono; Genentech, Inc.; Genmab A/S; HalioDX SAS; Halozyme; Imugene Limited; Inflection Biosciences Limited; Ipsen; Kura Oncology; Lilly; MSD; Menarini; VCN Biosciences. A. Grothey: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Full/Part-time employment: Array BioPharma; Research grant/Funding (self): Novartis; Research grant/Funding (self): Boehringer Ingelheim. R. Yaeger: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Full/Part-time employment: Array BioPharma; Research grant/Funding (self): Novartis; Research grant/Funding (self): Boehringer Ingelheim. A. Gollerkeri: Full/Part-time employment: Pfizer. K. Maharry: Full/Part-time employment: Pfizer. S. Kopetz: Advisory/Consultancy: Roche/Genentech; Advisory/Consultancy: EMD Serono; Advisory/Consultancy: Merck; Advisory/Consultancy: Karyopharma Therapeutics; Advisory/Consultancy: Amal Therapeutics; Advisory/Consultancy: Navire Pharma; Advisory/Consultancy: Symphogen; Advisory/Consultancy: Holy Stone; Advisory/Consultancy: Amgen; Advisory/Consultancy: Novartis; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Boston Biomedical; Advisory/Consultancy: AstraZeneca/MedImmune; Advisory/Consultancy: Bayer Healthcare; Advisory/Consultancy: Pierre-Fabre. All other authors have declared no conflicts of interest.