NEW YORK – The US Food and Drug Administration on Friday granted accelerated approval to Pfizer's Braftovi (encorafenib) plus Eli Lilly's Erbitux (cetuximab) with chemotherapy for patients with newly diagnosed, metastatic colorectal cancer whose tumors harbor a BRAF V600E mutation.
The agency approved Braftovi, a BRAF inhibitor, with the EGFR-targeting monoclonal antibody Erbitux and mFOLFOX6 chemotherapy based on results from the Phase III BREAKWATER clinical trial. In BREAKWATER, Pfizer initially randomized patients to three different treatment arms. Patients had to be BRAF V600E mutation-positive according to Qiagen's Therascreen PCR test.
In the first treatment arm, patients received Braftovi once daily and Erbitux every two weeks; in the second treatment arm, patients received Braftovi once daily and Erbitux and mFOLFOX6 every two weeks; and in the third treatment arm, patients received either mFOLFOX6 chemotherapy, FOLFOXIRI chemotherapy, or CAPOX chemotherapy, all with or without Genentech's Avastin (bevacizumab). However, Pfizer subsequently amended the trial and only randomized patients to either Braftovi-Erbitux-mFOLFOX6 or chemo.
Among the first 110 patients randomized to each arm, the overall response rate was 61 percent in the Braftovi-Erbitux-mFOLFOX6 arm, versus 40 percent in the control arm. The median duration of response was 13.9 months for patients on Braftovi-Erbitux-chemo versus 11.1 months in the control arm.
Although progression-free survival and overall survival data are not yet available from BREAKWATER, the FDA said that these outcomes will provide the post-marketing confirmatory evidence needed to convert the accelerated approval into a full approval.
In 2020, the FDA approved Braftovi and Erbitux for BRAF V600E metastatic colorectal cancer patients who'd received prior therapy. The new approval moves this indication to the treatment-naïve setting.