RELATIVITY-047 at 4 Years: What Long-Term Data Mean for Sarah’s Treatment Options
Panelists discuss the prioritization of immunotherapy over targeted therapy for BRAF-mutant metastatic melanoma, highlighting updated RELATIVITY-047 data supporting nivolumab plus relatlimab for its durable efficacy and favorable toxicity profile, and emphasizing the importance of individualized treatment selection based on evolving evidence, patient goals, and comparative analyses of combination regimens.
The discussion turned toward the application of long-term data for combination immunotherapies in treating BRAF-mutant metastatic melanoma. While direct trial comparisons are lacking, evidence from studies such as DREAMseq has shown that starting with immunotherapy provides better long-term outcomes than targeted BRAF/MEK inhibition. Panelists emphasized that for eligible patients, particularly younger ones, immunotherapy should be prioritized as first-line treatment. The choice between different combination regimens—namely, nivolumab with relatlimab or with ipilimumab—is then guided by considerations of efficacy, toxicity, and patient-specific goals.
Updated 4-year data from the RELATIVITY-047 trial support the use of nivolumab plus relatlimab, showing durable progression-free survival benefits with a more favorable toxicity profile than traditional ipilimumab-based regimens. One key takeaway was that monotherapy with PD-1 inhibitors is no longer considered an appropriate frontline option for patients with advanced, treatment-naive melanoma, as combination approaches have shown superior outcomes. For patients with BRAF mutations, while targeted therapy remains an option, the preference remains immunotherapy first, reserving BRAF/MEK inhibitors for later lines if needed.
An indirect comparison between the combination regimens was discussed using statistical methods that adjust for baseline differences between trials. This analysis found that both combination therapies have comparable efficacy, with survival curves aligning closely. However, nivolumab plus relatlimab appeared slightly more favorable in melanoma-specific survival—potentially due to the broader availability of second-line treatments today. Additionally, toxicity profiles clearly favored the relatlimab-based combination, reinforcing its value in delivering meaningful clinical benefits with a more manageable safety burden. This nuanced understanding helps clinicians better tailor treatment sequencing and combination choices in managing advanced melanoma.
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