e-Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2020

Encorafenib plus cetuximab with or without binimetinib for BRAF V600E metastatic colorectal cancer: Updated survival results from a randomized, three-arm, phase III study versus choice of either irinotecan or FOLFIRI plus cetuximab (BEACON CRC) (#242)

Timothy Price 1 , Scott Kopetz 2 , Axel Grothey 3 , Eric Van Cutsem 4 , Rona Yaeger 5 , Harpreet Singh Wasan 6 , Takayuki Yoshino 7 , Jayesh Desai 8 , Fortunato Ciardiello 9 , Fotios Loupakis 10 , Yong S Hong 11 , Neeltje Steeghs 12 , Tormod K Guren 13 , Hendrik-Tobias Arkenau 14 , Pilar Garcia-Alfonso 15 , Lorraine Chantrill 16 17 , Niall Tebbutt 18 , Andrew Strickland 19 , Chris Karapetis 20 , Felicity Murphy 21 , Ashwin Gollerkeri 22 23 , Kati Maharry 22 23 , Janna Christy-Bittel 22 23 , Josep Tabernero 24
  1. Medical Oncology Unit, Queen Elizabeth Hospital and University of Adelaide, Adelaide, SA, Australia
  2. MD Anderson Cancer Center, The University of Texas , Houston, TX, America
  3. West Cancer Center, Germantown, TN, America
  4. University Hospitals Gasthuisberg Leuven, KU Leuven, Leuven, Belgium
  5. Memorial Sloan Kettering Cancer Center, New York, NY, America
  6. Hammersmith Hospital, Imperial College Health Care Trust, London, England, United Kingdom
  7. National Cancer Center Hospital East, Kashiwa, Japan
  8. Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
  9. University of Campania, Naples, Italy
  10. Istituto Toscano Tumori, Pisa, Italy
  11. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
  12. Netherlands Cancer Institute, Amsterdam, Netherlands
  13. Department of Oncology, Oslo University Hospital, Oslo, Norway
  14. Sarah Cannon Research Institute UK Limited, London, England, United Kingdom
  15. Hospital General Universitario Gregorio Marañón, Madrid, Spain
  16. St Vincent’s Hospital, Sydney, NSW, Australia
  17. Illawarra Cancer Care Centre, Wollongong Hospital, Wollongong, NSW, Australia
  18. Medical Oncology, Austin Health, Melbourne, VIC, Australia
  19. Monash Health and Monash University, Melbourne, VIC, Australia
  20. Flinders Medical Centre and Flinders University, Adelaide, SA, Australia
  21. The Mater Hospital, Brisbane, QLD, Australia
  22. Pfizer Inc., Cambridge, MA, America
  23. Pfizer Inc., Boulder, CO, America
  24. Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain

Background: BEACON CRC is a randomized, phase 3 study which evaluated the triplet of encorafenib (ENCO) + binimetinib (BINI) + cetuximab (CETUX) and the doublet of ENCO + CETUX vs. investigator’s choice of irinotecan + CETUX or FOLFIRI + CETUX in patients (pts) with BRAFV600E metastatic colorectal cancer (mCRC) whose disease had progressed after 1-2 prior regimens in the metastatic setting. Primary endpoints were overall survival (OS) and objective response rate (ORR; by blinded central review) for triplet vs control. In a previous interim analysis, triplet and doublet improved OS and ORR versus standard of care. Here we report on an updated analysis.

Methods: Updated analysis includes 6 months of additional follow-up and response data for all randomized pts. The study is ongoing.

Results: Pts received triplet (n=224), doublet (n=220), or control (n=221). Median OS was 9.3 months (95% confidence interval [CI]:8.2, 10.8) for triplet and 5.9 months (95% CI:5.1-7.1) for control (hazard ratio [HR] (95% CI): 0.60 (0.47-0.75)). Median OS for doublet was 9.3 months (95% CI: 8.0-11.3) (HR vs. control: 0.61 (0.48-0.77). Confirmed ORR was 26.8% (95% CI: 21.1%-33.1%) for triplet, 19.5% (95% CI: 14.5%-25.4%) for doublet, and 1.8% (95% CI: 0.5%-4.6%) for control. Retrospective subgroup analyses suggested some pts may benefit more from triplet than doublet therapy (Table). Both triplet and doublet showed improved OS compared to control in all subgroups. Adverse events were consistent with prior analysis, with grade ≥3 adverse events in 65.8%, 57.4%, and 64.2% for triplet, doublet and control, respectively.

Conclusions: The updated analysis of the BEACON CRC study confirmed that encorafenib + cetuximab with or without binimetinib improved OS and ORR in previously treated pts with BRAF V600E mCRC compared with standard chemotherapy. Clinical trial information: NCT02928224.