Treatment of patients with BRAF V600–mutant melanoma includes BRAF/MEK-inhibitor combinations based on demonstrated benefits on progression-free survival ( PFS ) and overall survival ( OS ).
To better understand the proportion of patients who derive long-lived benefit and their characteristics, researchers have performed an updated analysis of overall survival and other endpoints from the COLUMBUS trial.
In Part 1 of COLUMBUS, 577 patients with advanced / metastatic BRAF V600‒mutant melanoma, untreated or progressed after first-line immunotherapy, were randomized 1:1:1 to Encorafenib ( Braftovi ) 450 mg QD + Binimetinib ( Mektovi ) 45 mg BID ( Encorafenib 450 + Binimetinib ) versus Vemurafenib ( Zelboraf ) 960 mg BID or Encorafenib 300 mg QD.
An updated analysis including progression-free survival, overall survival, objective response rate ( ORR ), and safety was conducted after an additional 24 months’ follow-up from the initial analysis.
The study is ongoing.
At data cutoff ( November 2019 ), events had occurred in 65%, 59%, and 75% of patients in the Encorafenib 450 + Binimetinib, Encorafenib 300, and Vemurafenib treatment arms, respectively.
Across arms, median follow-up for overall survival was 60.6 months, with median overall survival of 33.6 months ( 95% CI, 24.4–39.2 ) for Encorafenib 450 + Binimetinib, 23.5 months ( 95% CI, 19.6–33.6 ) for Encorafenib 300, and 16.9 months ( 95% CI, 14.0–24.5 ) for Vemurafenib.
Compared to Vemurafenib, Encorafenib 450 + Binimetinib decreased the risk of death by 38% ( hazard ratio, HR=0.62 [ 95% CI, 0.49–0.79 ] ).
Updated median progression-free survival was Encorafenib 450 + Binimetinib, 14.9 months ( 95% CI, 11.0–20.2 ), Encorafenib 300, 9.6 months ( 95% CI, 7.4–14.8 ), and Vemurafenib, 7.3 months ( 95% CI, 5.6–7.9 ).
Progression-free survival was longer for Encorafenib 450 + Binimetinib vs Vemurafenib ( HR=0.52 [ 95% CI, 0.40–0.67 ] ).
A landmark analysis showed a higher rate of overall survival for Encorafenib 450 + Binimetinib at each year analyzed, with overall survival rates at 4 years of 39%, 37%, and 26% Encorafenib 450 + Binimetinib, Encorafenib 300, and Vemurafenib, respectively.
Updated safety analysis confirmed the beneficial long-term tolerability of Encorafenib 450 + Binimetinib.
In conclusion, in the COLUMBUS trial, results for updated progression-free survival and overall survival with Encorafenib 450 + Binimetinib continue to demonstrate long-term benefits in patients with BRAF V600‒mutated melanoma. ( Xagena )
Source: American Society of Clinical Oncology ( ASCO ) Virtual Meeting, 2020