A dual institution real-world study of avelumab for advanced Merkel cell carcinoma

Merkelcell.org Summary

In this study, authors looked at how well avelumab, an immunotherapy drug, works in treating advanced Merkel cell carcinoma. They included patients who hadn’t gotten any treatment before and those who had received treatments like chemotherapy. The results showed that avelumab helped patients, with a 54% response rate for those who hadn’t gotten any prior treatment and 35% for those who had received previous treatments, regardless of their immune status. This study is important because it provides real-world data, which means they looked at how the drug works in regular medical practice, not just in controlled clinical trial. The findings in the real word data were consistent with previous clinical trials and provide further support for using immunotherapy as the initial treatment for advanced MCC.

Abstract

Background: Merkel cell carcinoma (MCC) is a rare, aggressive, cutaneous neoplasm with an increasing incidence rate and poor prognosis. The treatment landscape has changed dramatically over the last half decade, beginning with the 2017 approval of the anti-programmed death-ligand 1 (PD-L1) monoclonal antibody avelumab. Accelerated approval for avelumab was based on data from the JAVELIN Merkel 200 study, which demonstrated an objective response rate (ORR) of 33% in previously treated subjects (≥2L). In the first-line (1L) clinical-trial setting, avelumab was associated with an ORR of 40% and a durable response rate (DRR) of 30%. There are limited data regarding the efficacy of avelumab in the real-world setting.

Methods: We performed a Mass General Brigham (MGB) Institutional Review Board-approved retrospective study of patients with advanced MCC. Clinical data regarding the disease course, including diagnosis and treatment, were collected from the Electronic Health Record and stored in a REDCap database. Response category was assigned based on the text of the radiology reports and clinician notes. Analysis was performed in R.

Results: 1249 patients with MCC were identified; 260 received systemic therapy; 54 were treated with avelumab (our primary analysis cohort, PAC). Median age of the PAC was 74 years. 80% were male. 83% had an initial ECOG of 0 or 1. 20% were immunosuppressed at the time of MCC diagnosis. The real-world response rate (rwORR) for all patients treated with avelumab was 45.83%. rwORR in the 1L was 53.57% and 35% in the second line and beyond. The median duration of treatment response in the 1L was 518 days and 144 days for ≥2L. Median progression-free survival was 158 days and 95 days, and median overall survival was 553 days and 323 days for 1L and > 2L, respectively.

Conclusions: Our study provides important data about the real-world treatment of patients with advanced MCC. The response rate and progression-free survival were consistent with those observed in other real-world studies as well as the clinical trials. While the subjects studied in previously published studies differ from that in MGB cohort, the overall body of literature continues to demonstrate positive outcomes attributable to avelumab monotherapy in both the 1L as well as second-line or beyond and in patients with competent, as well as compromised, immune systems. Limitations of this study include its retrospective nature. Furthermore, given the small sample size, we are limited in making statistical inferences from the current data set and specific results may not be generalizable to all patients with MCC.