The U.S. Food and Drug Administration (FDA) has approved encorafenib (Braftovi®, Array BioPharma/Pfizer) in combination with cetuximab (Erbitux®; Eli Lilly and Company) for the treatment of adult patients with metastatic colorectal cancer (mCRC) with a BRAF V600E mutation, detected by an FDA-approved test, after prior therapy.
According to recent data from the American Cancer Society (ACS) colorectal cancer is the second most common cause of cancer death in the United States when men and women are combined. In 2020, an estimated 104,610 new cases of colon and 43,340 cases of rectal cancer are expected to be diagnosed, and an estimated 53,200 people are expected to die from the disease.
New treatment combination
The efficacy of the combination was evaluated in a randomized, active-controlled, open-label, multicenter, 3-arm Phase III study (NCT02928224). In this trial, eligible patients were required to have BRAF V600E mutation-positive metastatic CRC (detected by the Qiagen companion diagnostics’ therascreen® BRAF V600E RGQ PCR test) with disease progression after one or two prior regimens.
As part of the trial, 220 patients were randomized to encorafenib (300 mg orally once daily) in combination with cetuximab and 221 patients were randomized to the control arm of either irinotecan (OniIvyde®; Ipsen Biopharm) or FOLFIRI* with cetuximab.
The major efficacy outcome measure was overall survival (OS). Additional efficacy outcome measures included progression-free survival (PFS), overall confirmed response rate (ORR), and duration of response (DoR). ORR and DoR were assessed by blinded independent central review in the subset of the first 220 patients randomized to receive either encorafenib plus cetuximab or the control arm.
Median OS was 8.4 months (95% CI: 7.5, 11.0) in the encorafenib and cetuximab arm compared to 5.4 months (95% CI: 4.8, 6.6) in the control arm (HR 0.60; 95% CI: 0.45, 0.79; p=0.0003). Median PFS was 4.2 months (95% CI: 3.7, 5.4) in the encorafenib and cetuximab arm compared to 1.5 months (95% CI: 1.4, 1.7) in the control arm (HR 0.40; 95% CI: 0.31, 0.52; p< 0.0001). ORR was 20% (95% CI: 13%, 29%) and 2% (95% CI: 0%, 7%), respectively. Median DOR was 6.1 months (95% CI: 4.1, 8.3) for the encorafenib and cetuximab arm and not reached (95% CI: 2.6, NR) in the control arm.
The most common adverse reactions (≥25%) for encorafenib with cetuximab were fatigue, nausea, diarrhea, dermatitis acneiform, abdominal pain, decreased appetite, arthralgia, and rash.
* FOLFIRI is a chemotherapy regimen consisting of leucovorin calcium (calcium folinate), 5-fluorouracil (5FU), and irinotecan used in the treatment of advanced-stage and metastatic colorectal cancer.
Click here to view full prescribing information for encorafenib (Braftovi®, Array BioPharma/Pfizer)
Study of Encorafenib + Cetuximab Plus or Minus Binimetinib vs. Irinotecan/Cetuximab or Infusional 5-Fluorouracil (5-FU)/Folinic Acid (FA)/Irinotecan (FOLFIRI)/Cetuximab With a Safety Lead-in of Encorafenib + Binimetinib + Cetuximab in Patients With BRAF V600E-mutant Metastatic Colorectal Cancer (BEACON CRC) – NCT02928224
 Siegel RL, Miller KD, Goding Sauer A, et al. Colorectal cancer statistics, 2020 [published online ahead of print, 2020 Mar 5]. CA Cancer J Clin. 2020;10.3322/caac.21601. doi:10.3322/caac.21601