According to the phase 2 EBIN trial, there was no difference in progression-free survival between upfront combined immunotherapy and targeted therapy induction followed by combined immunotherapy for patients with advanced BRAF-V600E/K mutant melanoma.

These results were first presented by Carolina Robert, MD, Gustave Roussy Cancer Campus, Villejuif, France, at the 2024 American Society for Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

As Dr Robert explained, the optimal sequence of treatments for patients with advanced BRAF-V600E/K melanoma is combined immunotherapy followed by targeted therapy at progression. She added, “the benefit of induction treatment with targeted therapy followed by immunotherapy without waiting for progression is still unclear.”

In this trial, patients were randomized on a 1-to-1 basis to receive either combined, upfront immunotherapy with 3 mg/kg nivolumab plus 1mg/kg ipilimumab every 3 weeks for 4 cycles followed by 480 mg nivolumab every 4 weeks (combined immunotherapy arm, n = 131), or 3 months of targeted therapy induction with 450 mg encorafenib daily plus 45 mg binimetinib twice a day, followed by the combined immunotherapy regimen (sequential arm, n = 136), for a total treatment duration of 2 years in both arms. If patients in the sequential arm progressed, they were allowed to rechallenge with targeted therapy. The primary end point was superiority of the sequential arm in PFS, stratified by stage and lactate dehydrogenase (LDH).

Among the patients enrolled, there were 129 patients with LDH above upper limit normal and 74 patients with liver metastasis. At a median follow-up duration of 21 months, there was “no evidence of a longer PFS” in the sequential arm, as Dr Robert and coauthors stated (hazard ratio [HR], 0.87; P = .36). In a pre-specified subgroup analysis, the hazard ratio for the combined immunotherapy arm vs the sequential arm was 2.09 among  patients with LDH ≤ upper limit normal or M1a, 0.74 among patients with M1b/c with LDH ≤ upper limit normal, 0.86 among patients with LDH > upper limit normal but ≤ twice upper limit normal, and 0.46 among patients with LDH > twice upper limit normal. In a post-hoc subgroup analysis the treatment HR was 0.48 for patients with liver metastases.

While “there is no different in PFS between the two treatment arms for unselected patients,” Dr Robert concluded, “data supports the hypothesis that patients with very high LDH (>2ULN) and those with liver metastases benefit from the sequential approach in terms of PFS.”

Source:

Robert C, Dutriaux C, Oppong FB, et al. Combination of encorafenib and binimetinib followed by ipilimumab and nivolumab versus ipilimumab and nivolumab in patients with advanced BRAF-V600E/K-mutated melanoma: The primary analysis of an EORTC randomized phase II study (EBIN). Presented at 2024 ASCO Annual Meeting. May 31-June 4, 2024; Chicago, IL. Abstract #LBA 9503