First-Line Opdivo-Novel Therapy Combo More Than Doubles Survival in Advanced Skin Cancer


The use of Opdivo combined with the novel therapy relatlimab resulted in a significant improvement of progression-free survival compared to treatment with Opdivo, alone, in patients with previously untreated, unresectable or metastatic melanoma.

Treatment with a novel drug combination more than doubled progression-free survival in patients with previously untreated, unresectable or metastatic melanoma, compared to treatment with one drug.

The data, which were presented during a virtual news briefing ahead of the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, demonstrated that adding relatlimab to Opdivo (nivolumab) induced a median progression-free survival (time during and after treatment when a patient lives with cancer without disease progression) of 10.2 months versus 4.63 months with treatment with single-agent Opdivo.

Moreover, the 12-month progression-free survival (PFS) rate with the combination was 47.7% compared to 36% with single-agent Opdivo.

“Our findings demonstrate that relatlimab plus (Opdivo) is a potential novel treatment option for this patient population,” lead study author Dr. Evan J. Lipson, of the Bloomberg~Kimmel Institute for Cancer Immunotherapy and Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University in Baltimore, said in a presentation on the data.

Because PD-L1 inhibitors have been shown to improve survival in several tumor types, including melanoma, investigators began to examine novel immune checkpoint inhibitor combinations to derive further clinical benefit with manageable risk.

Relatlimab is an antibody that was developed to block LAG-3, which is responsible for T-cell inhibition and helps cancer cells avoid immune attacks. The agent is designed to help reinvigorate T cells to target cancer cells.

Previous data involving this combination showed that the doublet elicited an objective response rate of 11.5% with a disease control rate of 49% among 68 patients with melanoma who received previous immunotherapy. Notably, 57% of these patients had previously received an anti–CTLA-4 agent and 46% had received three more prior lines of treatment.

“In support of this approach are results from trials that led up to the current study in which administration of relatlimab plus (Opdivo) caused tumors to shrink in some patients with advanced melanoma who had already progressed through anti–PD-1 alone,” Lipson noted.

A total of 714 patients were enrolled onto the phase 2/3 trial and randomized them 1:1 to receive either a single fixed-dose intravenous (IV) infusion of 160 milligrams (mg) of relatlimab plus 480 mg of Opdivo every four weeks or 480 mg of IV Opdivo every four weeks.

“[The combination] is administered as a single intravenous infusion to reduce preparation and infusion times and minimize the risk of administration errors,” Lipson explained.

Measuring progression-free survival served as the main goal of the study. Other goals included evaluating overall survival (OS) and objective response rate.

Treatment with the combination was associated with a manageable safety profile, with no unexpected safety signals observed during the study. Among those who received the combination, 97.2% of patients experienced a side effect, of which 40.3% were considered more serious or severe; in the group who received single-agent Opdivo, these rates were 94.4% and 33.4%, respectively.

The most common treatment-related side effects reported in the combination group and single-agent group included itchy skin (23.4% vs 15.9%, respectively), fatigue (23.1% vs 12.8%), and rash (15.5% vs 12.0%). The most frequently experienced serious or severe treatment-related side effect in the combination group included fatigue (1.1%), rash (0.8%), joint pain (0.8%), and diarrhea (0.8%). In the single-agent group, the most notable serious or severe treatment-related side effects were itchy skin (0.6%), rash (0.6%) and diarrhea (0.6%).

Less than 15% (14.6%) of patients who received the combination experienced a treatment-related side effect that led to treatment discontinuation; 8.5% of which discontinued treatment due to serious or severe side effects. Comparatively, 6.7% and 3.1% of patients who received single-agent Opdivo, respectively, discontinued treatment. Three patients in the combination group died due to treatment-related hemophagocytic lymphohistiocytosis (rare, systemic inflammatory syndrome), acute edema of the lung and pneumonitis. In total, two patients in the single-agent Opdivo group died due to sepsis and myocarditis, as well as worsening pneumonia.

A follow-up study evaluating overall survival is currently underway.

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