Adjuvant immunotherapy with nivolumab (NIVO) versus observation in completely resected Merkel cell carcinoma (MCC): Disease-free survival (DFS) results from ADMEC-O, a randomized, open-label phase II trial

Merkelcell.org Summary

’Adjuvant’ therapy is given to patients when there is no clear evidence of cancer, but the goal is to decrease the risk the cancer will come back following initial therapy. In this meeting abstract presented at the European Society for Medical Oncology by Dr. Juergen Becker, the authors report early findings that suggest that giving adjuvant nivolumab (a PD1 inhibitory immune stimulating drug) decreases the risk that a patient’s MCC would recur by more than 40%. If subsequent work on this adjuvant trial (and several other trials ongoing around the world) continues in this direction, it would support the notion that for high-risk patients who can tolerate such a drug, adjuvant therapy may make sense. At this point, such therapy should be limited to clinical trials as the rigorous data are not in hand yet and insurance companies and cancer guidelines are not yet supportive of this approach.

Abstract

Background

MCC is a rare, immunogenic but aggressive skin cancer. Even after complete resection and radiation relapse rates are high. PD-1/PD-L1 immune checkpoint inhibitors (ICI) showed clinical benefit in locally advanced MCC. ADMEC-O is the first trial to investigate the efficacy/safety of adjuvant PD-1 blockade by ICI in completely resected MCC, i.e. in a situation with no systemic Standard of Care.

Methods

This multicenter phase 2 trial enrolled MCC patients (pts) (any stage, ECOG PS 0-1) with tumor lesions completely resected within 12 weeks prior to a 2:1 randomization to either NIVO 480 mg Q4W for up to 1 year, or observation, stratified by stage of disease (AJCC I/II vs. III/IV), age (<65 vs. ≥65 years) and gender. DFS was the primary endpoint, overall survival (OS) and adverse events (AE) secondary endpoints. This planned interim analysis was triggered when the Last Patient In was followed for at least 1 year.

Results

From 03/2017 until 08/2020 179 pts (NIVO, n=118; observation, n=61) were enrolled from 20 centers (ITT population; 62% male, 68% ≥65 years, 67% stage III/IV), with baseline characteristics well balanced across both arms. At this interim analysis with a median follow-up of 24.3 months (IQR 19.2-33.4), all pts had ended treatment. DFS rates at 12 and 24 months favored NIVO with 87.9% vs 78.5%, and 86.9% vs 74.3%, respectively. OS results are not yet mature. Treatment was well tolerated, with 41% of NIVO pts and 31% of pts in the observation group experiencing grade 3/4 AEs; only 5% of pts discontinued due to adverse events. No treatment-related deaths were reported. Table: 787O

* HR: hazard ratio for the median provided by a univariate Cox model; CI, Confidence interval; NR, not reached

Conclusions

In this first randomized trial for MCC, a hazard ratio for DFS of 0.56 (95% CI 0.28-1.15) in favor of NIVO was observed at a median follow-up of 2 years, suggesting clinical benefit in this unmet medical need. Remarkably, the spontaneous course of MCC was considerably better than historical data would have suggested.