Background Prior to the approval of immune checkpoint inhibitors, patients with metastatic Merkel cell carcinoma (mMCC), a rare and aggressive neuroendocrine skin carcinoma, had a poor prognosis (5-year overall survival [OS] rate of approximately 17%). Avelumab, an anti–PD-L1 antibody, has been approved in multiple countries for the treatment of mMCC based on the results of the phase 2 JAVELIN Merkel 200 trial (NCT02155647). In the primary analysis of part B of the trial, which investigated avelumab as first-line (1L) treatment for mMCC and was reported after 15 months of follow-up in all patients, the objective response rate was 39.7%, the durable (≥6 months) response rate was 30.2%, and median OS was 20.3 months. Here, we report findings after 4 years of follow-up.

Methods Eligible patients had histologically confirmed stage IV mMCC and had received no prior systemic therapy. Patients received avelumab 10 mg/kg intravenously every 2 weeks as monotherapy until confirmed disease progression, unacceptable toxicity, or withdrawal of consent. Here, patient disposition and long-term OS were analyzed.

Results A total of 116 patients received 1L avelumab treatment. At data cutoff (February 2, 2022), median follow-up was 54.3 months (range, 48.0-69.7 months) and 72 patients (62.1%) had died. At last follow-up, 7 patients (6.0%) remained on treatment and were progression-free, 22 patients (19.0%) had discontinued treatment but remained in follow-up, and 87 patients (75.0%) had discontinued from the trial. Reasons for treatment discontinuation were disease progression in 54 (46.6%), adverse event in 27 (23.3%), withdrawal of consent in 6 (5.2%), death in 5 (4.3%), loss to follow-up in 1 (0.9%), and other reasons in 16 (13.8%). Median OS was 20.3 months (95% CI, 12.4-42.0 months) and OS rates (95% CIs) after 2, 3, and 4 years were 49% (40%-58%), 44% (34%-53%), and 38% (29%-47%), respectively. Median OS was 38.7 months (95% CI, 11.3 months to not estimable) in patients with PD-L1+ tumors (n=21) and 16.1 months (95% CI, 9.6-42.0 months) in patients with PD-L1− tumors (n=87). Overall, 48 patients (41.4%) had received ≥1 subsequent anticancer drug therapy, most commonly etoposide (20 [17.2%]), carboplatin (18 [15.5%]), and avelumab (post-trial; 14 [12.1%]).

Conclusions Avelumab 1L monotherapy in patients with mMCC resulted in a 4-year OS rate of 38%. OS rates were numerically higher than those seen in historical studies of 1L chemotherapy. These results further support the use of avelumab as a standard-of-care treatment for patients with mMCC.

Acknowledgements This trial was sponsored by the healthcare business of Merck KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945) as part of an alliance between the healthcare business of Merck KGaA, Darmstadt, Germany and Pfizer. Medical writing support was provided by Eleanor Bishop of ClinicalThinking and was funded by the healthcare business of Merck KGaA, Darmstadt, Germany and Pfizer.

Trial Registration NCT02155647 (ClinicalTrials.gov)

Ethics Approval The trial protocol was approved by the independent ethics committee or institutional review board at each participating center