The updated survival results from the COLUMBUS trial of combination therapy with encorafenib plus binimetinib continued to show improvement over single-agent therapies and may represent a promising new treatment option for patients with BRAF V600–mutant melanoma. These results were presented (abstract 9512) during a poster session at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, held in Chicago.
“This is an update on the results presented at ASCO last year,” said study author Helen Gogas, MD, PhD, of the National and Kapodistrian University of Athens and Laikon Hospital in Greece. “[These results] led to the FDA registration of this combination for BRAF-positive patients.”
The COLUMBUS trial included 577 patients with advanced or metastatic BRAF V600–mutant melanoma who were either untreated or had progressed after first-line immunotherapy. They were randomized 1:1:1 to receive a combination of encorafenib (450 mg daily) plus binimetinib (45 mg twice daily); vemurafenib alone (960 mg twice daily); or encorafenib alone (300 mg daily).
The updated analysis included measures for progression-free survival (PFS), overall survival (OS), objective response rate (ORR), duration of response (DOR), and safety and tolerability. Patient data were also analyzed by prognostic subgroups, including elevated lactate dehydrogenase (LDH) levels and the degree of organ involvement.
“What is nice is that the curves for both PFS and OS continue to separate,” said Gogas, “and again with the extended follow-up, we have exactly the same median PFS for the combination in comparison with a single agent.”
The median follow-up duration for OS was 48.8 months; at that time, the median OS was 33.6 months (95% CI, 24.4–39.2 months) for combination therapy, 23.5 months (95% CI, 19.6–33.6 months) for encorafenib monotherapy, and 16.9 months (95% CI, 14.0–24.5 months) for vemurafenib monotherapy. The combination therapy decreased the risk of death by 39% compared with vemurafenib monotherapy (hazard ratio [HR], 0.61; 95% CI, 0.48–0.79).
The median PFS was 14.9 months (95% CI, 11.0–20.2 months) for the combination therapy, 9.6 months (95% CI, 7.4–14.8 months) for encorafenib monotherapy, and 7.3 months (95% CI, 5.6–8.2 months) for vemurafenib monotherapy. PFS was longer with the combination therapy than with vemurafenib monotherapy (HR, 0.52; 95% CI, 0.40–0.67).
Overall response was confirmed in both a blinded independent central review and a local review. In the central review, the ORR was 64% for patients in the combination therapy group, 52% for patients in the encorafenib monotherapy group, and 41% for patients in the vemurafenib monotherapy group. In the local review, these rates were 76%, 58%, and 49%, respectively.
The investigators reported safety and tolerability results consistent with the previous results. Grade 3/4 adverse event rates were 68% for the combination therapy, 68% for encorafenib monotherapy, and 66% for vemurafenib monotherapy. Treatment discontinuation rates were 16%, 15%, and 17%, respectively. Dose reduction rates were 55%, 71%, and 62% for the 3 groups, respectively.
All-cause mortality rates were 13%, 8%, and 11% for patients in the combination, encorafenib, and vemurafenib groups, respectively.
“The updated results are reassuring [in] that we didn’t have any surprises,” concluded Gogas.