The phase 3, randomized BEACON trial that evaluated chemotherapy-free triplet and doublet regimens in patients with metastatic colorectal cancer (mCRC) harboring a BRAF V600E mutation has been described as “the single worst” trial by Vinay Prasad, MD, MPH, Oregon Health & Science University. However, several of the criticisms that he made during an episode of his podcast Plenary Session do not appear to be shared widely by oncologists who specialize in CRC.1
For example, Dr Prasad argued that the control arm was “flawed” and that cetuximab has “no role” by itself in BRAF V600E-mutated CRC.
Recently reported in the New England Journal of Medicine, the BEACON trial randomly assigned patients to 1 of 3 treatment arms: a triplet regimen of encorafenib, binimetinib, and cetuximab, a doublet regimen of encorafenib and cetuximab, or the control group, in which patients received the investigators’ choice of cetuximab and irinotecan or cetuximab and FOLFIRI (folinic acid, fluorouracil, and irinotecan).2
And while clinical trials have shown that cetuximab in combination with a chemotherapy regimen is largely ineffective for this patient population, at the time when the trial was initiated in 2016, cetuximab and irinotecan or cetuximab and FOLFIRI were still being used in clinical practice.3
“Hindsight is 20-20,” Marwan Fakih, MD, medical oncologist at City of Hope, Duarte, California, and codirector of City of Hope’s Gastrointestinal Cancer Program, told Cancer Therapy Advisor (Dr Fakih was not involved in the BEACON trial). He agreed that now, cetuximab plus irinotecan is known to be “not very effective” in the second- or third-line setting.
Another criticism was the lack of “basic” information reported in the manuscript, such as not reporting how many patients on the control arm received which regimen, the therapies received before and after study treatment, how long patients had been living with a metastatic cancer diagnosis before study enrollment, and the proportion of patients who had de novo stage 4 disease compared with those who initially had localized disease that metastasized at relapse. The concern was that these factors could have affected median overall survival (OS), which was 9 months in the triplet arm, 8.4 months in the doublet arm, and 5.4 months in the control arm.1,2