As reported in The Lancet by Becker et al, an interim analysis of a European phase II study (ADMEC-O) showed that adjuvant nivolumab was associated with a numeric benefit in disease-free survival vs observation in patients with completely resected Merkel cell carcinoma.
Study Details
In the open-label trial, 179 patients from sites in Germany and the Netherlands were randomly assigned 2:1 between October 2014 and August 2020 to receive nivolumab at 480 mg every 4 weeks for 1 year (n = 118) or observation (n = 61). Adjuvant radiotherapy was more common in the control group (surgery plus radiotherapy in 74% vs 50%). The primary endpoint was landmark disease-free survival at 12 and 24 months in the intention-to-treat population.
Disease-Free Survival
Median follow-up at interim analysis was 24.3 months (interquartile range = 19.2–33.4 months). Median disease-free survival was not reached in either group. For the nivolumab group vs the control group, disease-free survival was 85% (95% confidence interval [CI] = 77%–91%) vs 77% (95% CI = 64%–86%) at 1 year and 84% (95% CI = 76%–90%) vs 73% (95% CI = 59%–83%) at 2 years (hazard ratio [HR] = 0.58, 95% CI = 0.30–1.12).
KEY POINTS
- Disease-free survival was 85% in the nivolumab group vs 77% in the control group at 1 year.
- Rates at 2 years were 84% vs 73%.
Overall survival results were not mature. For the nivolumab group vs the control group, overall survival was 94% (95% CI = 87%–97%) vs 96% (95% CI = 87%–99%) at 1 year and 94% (95% CI = 87%–97%) vs 92% (95% CI = 80%–97%) at 2 years.
Adverse Events
Grade 3 or 4 adverse events occurred in 48 (42%) of 115 patients who received at least one dose of nivolumab and 7 (11%) of 61 patients in the control group. Adverse events were considered treatment-related in 20% of the nivolumab group; the most commonly reported events in the nivolumab group were increased lipase (4%) and rash (3%). Treatment-related adverse events led to discontinuation of nivolumab in 21% of patients. Immune-mediated adverse events occurred in 61% of patients in the nivolumab group and were grade 3 or 4 in 16%. No treatment-related deaths were reported.
The investigators concluded, “Adjuvant therapy with nivolumab resulted in an absolute risk reduction of 9% (1-year disease-free survival) and 10% (2-year disease-free survival). The present interim analysis of ADMEC-O might suggest clinical use of nivolumab in this area of unmet medical need. However, overall survival events rates, with 10 events in the active treatment group and 6 events in the half-the-size observation group, are not mature enough to draw conclusions. The explorative data of our trial support the continuation of ongoing, randomized trials in this area. ADMEC-O suggests that adjuvant immunotherapy is clinically feasible in this area of unmet medical need.”
Dirk Schadendorf, MD, of University Hospital Essen, is the corresponding author for The Lancet article.
Disclosure: The study was funded by Bristol Myers Squibb. For full disclosures of the study authors, visit thelancet.com.
