KEY TAKEAWAYS
- The COLUMBUS phase 3 trial aimed to evaluate 7-year outcomes of Enco + Bini vs Enco alone in BRAF V600–mutant metastatic melanoma.
- The result concluded that Enco + Bini shows sustained efficacy & safety in BRAF V600 melanoma over 7 years.
In the randomized, two-part, multicenter investigation Phase 3 COLUMBUS study, the combination therapy of Encorafenib (Enco) and Binimetinib (Bini), as well as the solitary administration of Enco demonstrated significant enhancements in both progression-free survival (PFS) and overall survival (OS) rates when compared to vemurafenib (Vemu). These favorable outcomes were observed in patients grappling with metastatic melanoma harboring the BRAF V600 mutation.
Herein, Andrew M. Haydon and other researchers presented the findings derived from the exhaustive 7-year analysis carried out in the context of COLUMBUS part 1.
In the interventional study, advanced or metastatic melanoma patients characterized by the BRAF V600 mutation underwent a 1:1:1 randomization to receive either enco 450 mg once daily plus bini 45 mg twice daily, vemu 960 mg twice daily or enco 300 mg once daily. These patients were either treatment (tx)-naive or experienced disease progression after first-line (1L) immunotherapy, with no prior use of BRAF/MEK inhibitors. Randomization was stratified based on cancer stage (IIIB + IIIC + IVM1a + IVM1b vs IVM1c), ECOG performance status (0 vs 1), and prior 1L immunotherapy (yes vs no).
About 577 patients were randomly assigned to receive either enco + bini (n=192), vemu (n=191), or enco alone (n=194). The updated analyses were performed with a minimum follow-up of more than 93 months. In the enco + bini arm, the 7-year PFS and OS rates were 21.2% (95% CI: 14.7, 28.4) and 27.4% (95% CI: 21.2, 33.9), respectively. For the vemu arm, the corresponding rates were 6.4% (95% CI: 2.1, 14.0) for PFS and 18.2% (95% CI: 12.8, 24.3) for OS.
Treatment-emergent adverse events (TEAEs) occurring in ≥30% of patients with enco + bini included nausea, diarrhea, vomiting, arthralgia, and fatigue. Grade 3/4 TEAEs with ≥5% incidence in the enco + bini group were increased γ-glutamyltransferase, increased blood creatine phosphokinase, hypertension, increased alanine aminotransferase (ALT), and anemia.
Across all treatment arms, 16% to 20% of patients discontinued treatment due to adverse events. Following treatment discontinuation, 15% of patients from the enco + bini arm, 42% from the vemu arm, and 28% from the enco alone arm received BRAF/MEK inhibitor treatment. Additionally, 42% from the enco + bini arm, 49% from the vemu arm, and 43% from the enco alone arm received checkpoint inhibitors.
The result concluded that with a median follow-up duration of 100 months, the 7-year analysis of COLUMBUS part 1 affirms the enduring efficacy and established safety profile of enco + bini in patients with BRAF V600–mutant metastatic melanoma. There were no indications of new safety concerns emerging from the long-term follow-up.
This study is sponsored by Pfizer.
Source: https://cslide.ctimeetingtech.com/asia2023/attendee/confcal/show/session/78
Clinical Trial: https://clinicaltrials.gov/study/NCT01909453
Haydon AM, Schadendorf D, Dummer R, et al. “COLUMBUS 7-year update: A randomized, open-label, phase III trial of encorafenib (Enco) + binimetinib (Bini) vs vemurafenib (Vemu) or Enco in patients (Pts) with BRAF V600-mutant melanoma.” Presented at ESMO Asia Congress 2023. (Abstract: 602P).
