ANCHOR CRC: Triple therapy combo improves ORR in BRAF V600E-mutant mCRC

The combination of encorafenib (ENCO) + binimetinib (BINI) + cetuximab (CETUX) improves objective response rate (ORR) in patients with BRAF^V600E-mutant metastatic colorectal cancer (mCRC) in the first-line setting, according to the ANCHOR CRC* trial presented at ESMO GI 2020.

“BRAF^v600e mutation occurs in 10–15 percent of patients with mCRC and confers a poor prognosis,” according to lead author Dr Axel Grothey from West Cancer, University of Tennessee in Germantown, Tennessee, US. “[Moreover,] recent studies with chemotherapy-based regimens have shown poor outcomes”. [Br J Cancer 2009;101:715-721]

This stage 1 analysis of ANCHOR CRC evaluated 40 patients (mean age 67 years, 61 percent were aged ≥65 years) with centrally confirmed BRAF^v600E-mutant mCRC who had no prior treatment with any RAF, MEK, or anti-EGFR inhibitors. Participants received oral ENCO 300 mg QD and BINI 45 mg BID + intravenous CETUX (250 mg/m² after a first dose of 400 mg/m²) weekly for the first 28 weeks, followed by once every 2 weeks (500 mg/m²). Patients continued treatment until disease progression, unacceptable toxicity, or consent of study withdrawal. [ESMO GI 2020, abstract LBA-5]

At baseline, 78 percent and 51 percent of patients had metastases in ≥2 organs and peritoneal metastasis, respectively. 

As per the investigator’s assessment, a high confirmed ORR was noted in 50 percent (95 percent confidence interval [CI], 34–66) of patients, with 85 percent demonstrating a reduction in tumour size (partial response [50 percent] and stable disease [35 percent]).

The median progression-free survival was 4.9 months (95 percent CI, 4.4–8.1).

The most common grade ≥3 adverse events (AEs) reported were diarrhoea (15 percent), anaemia (12 percent), and acute kidney injury (12 percent). “[Most] AEs were comparable to those observed with the same triple combination in BEACON [CRC]** study,” Grothey noted. [NEJM 2019;381:1632-1643]

“Despite the high risk features of the population enrolled in stage 1, including high proportion of patients ≥65 years old and advanced stage at diagnosis (multiple metastatic sites with frequent peritoneal carcinomatosis), most patients [who received the first-line therapy of ENCO + BINI + CETUX] had tumour regression,” Grothey said. 

“[Therefore,] having reached the minimal number of confirmed responses in stage 1, the futility analysis allowed for enrolment of additional patients in stage 2, [which is still ongoing],” Grothey added.

“The triplet combination was well tolerated and manageable with no unexpected toxicities,” he noted.

*ANCHOR CRC: encorAfenib, biNimetinib and Cetuximab in subjects witH previOusly untreated BRAF-mutant ColoRectal Cancer

**BEACON CRC: 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