1117P - Overall survival (OS) in patients with metastatic BRAF V600-mutant melanoma treated with encorafenib plus binimetinib (ENCO+BINI): Comparing real-world vs clinical trial data

Background

ENCO+BINI, a combination BRAF and MEK inhibitor therapy, prolonged OS in patients with BRAF V600-mutant metastatic melanoma in the multinational, phase III COLUMBUS clinical trial. We assessed how the real-world effectiveness of ENCO+BINI compares to efficacy observed in clinical trials after accounting for differences in patient profiles across these settings.

Methods

Patients treated with ENCO+BINI were drawn from the COLUMBUS trial and from Flatiron Health, an EMR-derived database of academic and community cancer clinics in the US. Included patients were adults with metastatic BRAF V600E/K mutated melanoma without central nervous system metastases who were untreated or had prior 1L immunotherapy (IO) and ECOG performance status (PS) of 0/1. OS was compared between ENCO+BINI patients treated in Flatiron vs. COLUMBUS, adjusting for age, sex, race, BMI, ECOG PS, LDH, prior 1L IO, prior medication/surgery, time since metastasis, and time from initial diagnosis to metastasis.

Results

This study included 275 patients treated with ENCO+BINI (192 from COLUMBUS, 83 from Flatiron). At baseline, patients in Flatiron had worse LDH (42% > ULN vs 29%), worse ECOG (46% vs 29% with ECOG PS of 1), and were more likely to have had prior 1L IO (36% vs 9%). Fewer patients in Flatiron had therapies after ENCO+BINI discontinuation (28% vs 43%). Survival at one (75% vs 75%) and 2 years (52% vs 58%) was similar, while median OS was numerically shorter in Flatiron (24.0 vs 33.6 months; p=0.35). OS was not significantly different between Flatiron and COLUMBUS in adjusted analyses (HR: 1.03 [0.62, 1.72]; p=0.90). Adjustments for sites/number of metastases and subsequent therapies, which may impact longer-term OS, may warrant consideration in the future.

Conclusions

Real world data suggests that clinical outcomes, including OS, for patients with metastatic BRAF V600-mutant melanoma treated with ENCO+BINI, are similar to those from trials, after accounting for differences in patient profiles. This indicates that clinical trial efficacy of ENCO+BINI translates to effectiveness in a broader real-world population, including patients treated with prior 1L IO.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Pfizer Inc.

Disclosure

G.K. In: Financial Interests, Personal, Principal Investigator: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Merck; Financial Interests, Personal, Advisory Board: Novartis, Bristol Myers Squibb, Regeneron, Sanofi, Castle Biosciences, Array; Financial Interests, Institutional, Principal Investigator: Regeneron, Idera, Array Biosciences, Xencor, Checkmate Pharmaceuticals, Instil Bio. K. Chen: Other, Institutional, Full or part-time Employment: Pfizer Inc. G. Sajeev, R. Simpson, S. Kalia, D. Christensen, D. Liu, J. Signorovitch: Other, Institutional, Full or part-time Employment: Analysis Group, Inc. which received consulting fees from Pfizer for this research. N. Rezai: Financial Interests, Institutional, Full or part-time Employment: Pfizer Inc. A. di Pietro: Financial Interests, Institutional, Full or part-time Employment: Pfizer Slr.