Lung cancer benefits from the combination of EGFR-TK inhibitors and patritumab deruxtecan17/01/2022
Encouraging results with polatuzumab vedotin in lymphoma patients31/01/2022
In patients with untreated, advanced melanoma, the combination of two immune checkpoint inhibitors increase progression-free survival
Together with the PD-1 inhibitor nivolumab relatlimab, a novel antibody that blocks an immune checkpoint found on the surface of T cells, offers benefit in patients with advanced melanoma: as shown in a paper on New England Journal of Medicine, progression-free survival rates were 47.7% in the combination therapy arm versus 36% in the nivolumab monotherapy arm.
The international, multicentric phase II/III Relativity-047 clinical trial enrolled 714 patients with untreated, unresectable stage III or IV melanoma. Patients were randomized to receive a fixed dose combination of relatlimab and nivolumab or nivolumab alone intravenously every four weeks. At the time of data cutoff in March 2021, median follow-up was more than 13 months, with 65.8% of patients having discontinued treatment mostly because of disease progression (36.3% in the combination arm vs 46% in the monotherapy arm). The progression-free survival rates were 47.7% in the combination arm versus 36% in the monotherapy arm, with a 25% lower risk of disease progression or death in the combination arm. Treatment-related adverse events occurred more frequently in the combination arm (18.9% vs. 9.7% in the monotherapy arm) but no new safety signals were identified and safety profile was manageable, with no differences in health-related quality of life across both treatment arms.
Lead author Hussein Twabi, MD Anderson Cancer Center, said: «The results from this global effort advance the field of immunotherapy by establishing a third class of immune checkpoint inhibitors through the LAG-3 pathway (lymphocyte-activation gene 3, an immune checkpoint on T cells, ed.) and have the potential to be practice-changing. We’ve seen historic developments in melanoma treatment over the last decade with the combination of PD-1 and CTLA-4 inhibitors, which work well but also carry substantial toxicity. This study represents a significant and long-awaited next step toward providing patients with effective and safer treatment options». The Food and Drug Administration granted priority review to the combination in September 2021 based on the results of Relativity-047 study. «We now have evidence of a clear benefit for combination therapy compared to single-agent PD-1 inhibitors, regardless patient subgroups (such as tumor stage or PD-1 and LAG-3 expression, ed.), and we’re looking forward to seeing response and overall survival data», said Tawbi.