Melanoma: immunotherapy works best in the morning

Melanoma immunotherapy is more effective and has fewer side effects when administered in the morning. This is one of the data from the multicenter Phase III CheckMate 238 trial, the first to confirm the 10-year efficacy of adjuvant immunotherapy, that is, administered after surgery in patients with high-risk resected melanoma. The work was presented by Paolo Ascierto, full professor of Oncology at the Federico II University and director of the Melanoma Oncology, Oncology Immunotherapy and Innovative Therapies Unit at the Pascale Institute in Naples, Italy, at the annual congress of the European Society For Medical Oncology (ESMO), under way in Berlin. The findings were published in the New England Medical Journal of Medicine.

"These data represent the longest follow-up ever recorded for an immunotherapy administered after melanoma surgery," Ascierto explained. A subsequent post-hoc analysis also suggests potentially better efficacy and tolerability of immunotherapy administered before 1 p.m., a finding that warrants further evaluation."

The study involved a total of 906 patients with high-risk resected melanoma, divided into 2 groups: in the first, patients received the drug nivolumab and in the second, ipilimumab. All patients were followed for about 10 years. "Well, nivolumab, an inhibitor of PD-1, one of the 'brakes' that prevent the immune system from attacking the tumor, demonstrated superior and durable efficacy compared with ipilimumab monotherapy on both relapse-free survival and distant metastasis-free survival," Ascierto reports.

Specifically, the 10-year recurrence-free survival rate was 44 percent for patients treated with nivolumab, compared with 37 percent for those treated with ipilimumab. A similar gap was also observed on distant metastasis-free survival: 54 percent in the nivolumab group compared with 48 percent in the ipilimumab group. More similar were the 10-year overall survival rates of 69 percent with nivolumab and 65 percent with ipilimumab. "Slight, but still significant, differences were again found in progression-free survival at second-line therapy: the analysis shows the superiority of nivolumab, with 10-year rates of 55%, compared with 47% for ipilimumab," Ascierto points out.

In a separate analysis on the same cohort of patients, the researchers made a surprising finding. Patients who received immunotherapy in the morning, specifically before 1 p.m., had a 10-year relapse-free survival of 44 percent versus 38 percent for those who received it in the afternoon. "Even wider is the discrepancy among patients who received ipilimumab alone: 43% recurrence-free survival in the morning versus 34%," Ascierto points out. In addition, the data indicate a numerically higher frequency of treatment-related adverse events with afternoon versus morning administration for both drugs. Thus, it is clear that the circadian rhythm influences the efficacy and tolerability of immunotherapy, a line of research that deserves further investigation."