Dr Bhatia on Adjuvant Avelumab in Patients With Merkel Cell Carcinoma and Lymph Node Metastases

“[The] HR was an impressive 0.55, with a P value of .07, which does not quite meet the level of statistical significance, but we feel that the results are going to be very meaningful in the clinic.”

Shailender Bhatia, MD, director of the Melanoma and Renal Cancer Team and a professor in the Clinical Research Division at Fred Hutch Cancer Center, the Lyn and Daniel Lerner Endowed Chair for Merkel Cell Carcinoma, and a professor in the Division of Hematology and Oncology at the University of Washington, discussed primary results from the phase 3 ADAM trial (NCT03271372) evaluating adjuvant avelumab (Bavencio) in patients with Merkel cell carcinoma (MCC) and clinically detected lymph node metastases.

The investigator-initiated study, conducted without a contract research organization or cooperative group, randomly assigned 100 patients with stage III MCC after definitive surgery or radiation to adjuvant avelumab (n = 48) or placebo (n = 52); Bhatia credited the multi-institutional academic collaboration for completing the trial with limited resources.

Safety with avelumab was consistent with prior experience with immune checkpoint inhibitors in the adjuvant setting, Bhatia said, reporting a grade 3 or higher treatment-related adverse effect rate of approximately 15% and a discontinuation rate of 7% to 8% due to toxicity.

For the primary end point of relapse-free survival (RFS), patients in the placebo arm experienced disease relapse at a rate of approximately 40%, with most recurrences in the first year, Bhatia noted. In the avelumab arm, only 12% of patients had relapsed at 1 year, representing an absolute risk reduction of 28%, although Bhatia observed later recurrences in years 2 and 3 before the curve appeared to stabilize. Because the avelumab arm was, on average, 5 years older than the placebo arm, non-MCC deaths may have pulled down the composite RFS curve, Bhatia explained; the adjusted HR for RFS was 0.55 (P = .07). An exploratory analysis of relapse events alone showed an HR of 0.47, a roughly 50% reduction in relapse risk, according to Bhatia. Distant metastasis-free survival also favored avelumab, though to a lesser degree than RFS, he said. MCC-specific survival was favorable in both arms, suggesting that patients who relapsed on placebo were effectively salvaged with subsequent immunotherapy, Bhatia said.

Bhatia concluded that the findings will help inform clinic discussions and allow individualization of the risk-benefit calculus of adjuvant therapy in MCC.