Highlights on melanoma/skin cancer 3

Prof Dr Jean-François Baurain, a medical oncologist at the Cliniques Universitaires Saint-Luc, Brussels presents an update on advanced melanoma from ASCO.

An updated analysis of the RELATIVITY-047 trial, which compared nivolumab monotherapy to a combination of nivolumab and relatlimab in patients with previously untreated metastatic or unresectable melanoma, has demonstrated an OS benefit with the combination therapy. The median OS for the nivolumab and relatlimab combination is reported at 51 months, which is comparable to the median OS observed with the nivolumab and ipilimumab combination. Clinicians are keen to determine the optimal first-line therapy for this patient population. Although an indirect comparison between the nivolumab-relatlimab and nivolumab-ipilimumab regimens did not reveal a significant difference in efficacy, there seems to be a notable difference in toxicity profile. First-line treatment with nivolumab and relatlimab is associated with lower toxicity, but these findings should be interpreted with caution due to differences in study designs and the evolving treatment landscape.

The benefit of induction treatment with targeted therapy using BRAF and MEK inhibitors prior to dual immunotherapy in patients with advanced BRAF-V600E/K mutant melanoma remains uncertain. The EBIN study, an EORTC randomized phase II trial, assessed the efficacy of an initial treatment with encorafenib and binimetinib followed by ipilimumab and nivolumab, compared to ipilimumab and nivolumab alone in patients with advanced BRAF-V600E/K-mutated melanoma. The study results indicated a clear initial benefit of starting with targeted therapy; however, this advantage rapidly diminished, showing no long-term benefit. A post-hoc subgroup analysis revealed that patients with very high lactate dehydrogenase levels and those with liver metastases experienced improved outcomes from the sequential treatment approach.

Immunotherapy is the current standard of care for advanced melanoma; however, a majority of patients do not achieve long-term benefit. The combination of pembrolizumab with lifileucel, a tumor-infiltrating lymphocyte (TIL) cell therapy, has demonstrated promising efficacy and durability in patients with untreated advanced melanoma and will be further evaluated in a phase 3 study. Additionally, the RELATIVITY-048 study investigated the triplet combination of nivolumab, relatlimab, and ipilimumab, showing encouraging efficacy without introducing new safety concerns. This combination will be further assessed in larger clinical trials.

In the second-line treatment of advanced melanoma, the ILLUMINATE 301 study with tilsotolimod added to ipilimumab did not improve response rates or overall survival (OS) in patients with PD-1 refractory advanced melanoma. These findings underscore the importance of moving away from arbitrary second-line treatments and highlight the necessity of using biomarkers to select appropriate patients for therapy.

Prof Baurain concludes his overview by highlighting some promising research in the second-line treatment for advanced melanoma as well as in uveal melanoma.