Abstract
Background: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer that has a poor prognosis in patients with advanced disease. Avelumab [anti-programmed death-ligand 1 (PD-L1)] became the first approved treatment for patients with metastatic MCC (mMCC), based on efficacy and safety data observed in the JAVELIN Merkel 200 trial. We report long-term overall survival (OS) data after >5 years of follow-up from the cohort of patients with mMCC whose disease had progressed after one or more prior lines of chemotherapy. Patients and methods: In Part A of the single-arm, open-label, phase II JAVELIN Merkel 200 trial, patients with mMCC that had progressed following one or more prior lines of chemotherapy received avelumab 10 mg/kg by intravenous infusion every 2 weeks until confirmed disease progression, unacceptable toxicity, or withdrawal. In this analysis, long-term OS was analyzed. Results: In total, 88 patients were treated with avelumab. At data cut-off (25 September 2020), median follow-up was 65.1 months (range 60.8-74.1 months). One patient (1.1%) remained on treatment, and an additional patient (1.1%) had reinitiated avelumab after previously discontinuing treatment. Median OS was 12.6 months [95% confidence interval (CI) 7.5-17.1 months], with a 5-year OS rate of 26% (95% CI 17% to 36%). In patients with PD-L1+ versus PD-L1− tumors, median OS was 12.9 months (95% CI 8.7-29.6 months) versus 7.3 months (95% CI 3.4-14.0 months), and the 5-year OS rate was 28% (95% CI 17% to 40%) versus 19% (95% CI 5% to 40%), respectively (HR 0.67; 95% CI 0.36-1.25). Conclusion: Avelumab monotherapy resulted in meaningful long-term OS in patients with mMCC whose disease had progressed following chemotherapy. These results further support the role of avelumab as a standard of care for patients with mMCC.
| Original language | English |
|---|---|
| Article number | 100290 |
| Journal | ESMO Open |
| Volume | 6 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 12.2021 |
Funding
This trial was sponsored by Merck (CrossRef Funder ID: 10.13039/100009945), Germany, as part of an alliance between Merck, Germany and Pfizer, United States. Medical writing support was provided by Felicia Barklund of ClinicalThinking and funded by Merck, Germany and Pfizer, United States (no grant number). The authors thank the patients and their families, investigators, co-investigators, and study teams at each of the participating centers. This trial was sponsored by Merck (CrossRef Funder ID: 10.13039/100009945), Germany, as part of an alliance between Merck, Germany and Pfizer, United States. Medical writing support was provided by Felicia Barklund of ClinicalThinking and funded by Merck, Germany and Pfizer, United States (no grant number). SPD has served in a consulting or advisory role for Adaptimmune, Amgen, GlaxoSmithKline, Immune Design, Immunocore, Incyte, Merck, and Nektar; has received travel and accommodations expenses from Adaptimmune, Merck, and Nektar; and has received institutional research funding from Amgen, Bristol Myers Squibb, Deciphera, Incyte, Merck, MSD, and Nektar. SB has served in a consulting or advisory role for Bristol Myers Squibb, Exicure, Genentech/Roche, Merck, and Sanofi/Regeneron (self and institution); has received travel and accommodations expenses from NantWorks and Sanofi/Regeneron; has received honoraria from Bristol Myers Squibb, Genentech/Roche, Merck, and Sanofi/Regeneron; and has received institutional research funding from Bristol Myers Squibb, Exicure, Immune Design, Merck, MSD, NantWorks, Nektar, Novartis, OncoSec, and Incyte. ASB has served in a consulting or advisory role for Bayer, Deciphera, and Merck; and their immediate family member has provided expert testimony for GlaxoSmithKline. OH has served in a consulting or advisory role for Aduro Biotech, Akeso Biopharma, Amgen, BeiGene, BioAtla, Bristol Myers Squibb, Genentech, GlaxoSmithKline, Idera, Immunocore, Incyte, Janssen, MSD, NextCure, Novartis, Pfizer, Regeneron, Roche, Sanofi, Seattle Genetics, Tempus, and Zelluna; has provided speaker services for Bristol Myers Squibb, Novartis, Sanofi/Regeneron, and Pfizer; has received honoraria from Bristol Myers Squibb, Pfizer, Novartis, and Sanofi/Regeneron; and has received institutional research funding from Aduro Biotech, Akeso Biopharma, Amgen, Arcus Biosciences, BioAtla, Bristol Myers Squibb, CytomX Therapeutics, Exelixis, Genentech, GlaxoSmithKline, Idera, Immunocore, Incyte, Iovance Biotherapeutics, Merck, MSD, Moderna Therapeutics, NextCure, Novartis, Pfizer, Regeneron, Roche, Sanofi, Seattle Genetics, Torque, and Zelluna. JMM has served in a consulting or advisory role for Bristol Myers Squibb, MSD, Sanofi/Regeneron, and Seattle Genetics; has received travel and accommodations expenses from Array BioPharma, Bristol Myers Squibb, Merck, and MSD; has stock and other ownership interests with Pfizer; has received honoraria from Merck and Pfizer; and has received institutional research funding from Amgen, AstraZeneca, Bristol Myers Squibb, Incyte, MacroGenics, MSD, Novartis, and Regeneron. PT has served in a consulting or advisory role for Bristol Myers Squibb, Merck, Novartis, Pierre Fabre, Roche, and Sanofi; has received travel and accommodations expenses from Bristol Myers Squibb and Pierre Fabre; and has received honoraria from Bristol Myers Squibb, CureVac, Merck, MSD, Novartis, and Roche. CL has served in a consulting or advisory role for Amgen, Bristol Myers Squibb, Merck, MSD, Novartis, Pierre Fabre, Roche, and Sanofi; has provided speaker services for Amgen, Bristol Myers Squibb, Novartis, MSD, and Roche; has received travel and accommodations expenses from Bristol Myers Squibb, MSD, Novartis, Pierre Fabre, and Sanofi; reports other relationships with Avantis Medical Systems; has received honoraria from Amgen, Bristol Myers Squibb, Incyte, MSD, Novartis, Pfizer, Pierre Fabre, and Roche; and has received institutional research funding from Bristol Myers Squibb and Roche. KDL has served in a consulting or advisory role for Array BioPharma, Iovance Biotherapeutics, Merck, Regeneron, Roche, and Sanofi; has received travel and accommodations expenses from Alkermes, Merck, Neon Therapeutics, Regeneron, and Roche/Genentech; has received honoraria from Array BioPharma and Iovance Biotherapeutics; has received institutional research funding from Alkermes, Array BioPharma, Bristol Myers Squibb, Incyte, Iovance Biotherapeutics, Kartos Therapeutics, Merck, Nektar, Neon Therapeutics, OncoSec, Regeneron, Roche/Genentech, and Ultimovacs; and has uncompensated relationships with Regeneron and Roche/Genentech. MM has served in a consulting or advisory role for Novartis and Pfizer and has received travel and accommodations expenses from Novartis. HX is an employee of EMD Serono Research & Development Institute, Inc. Billerica, MA, USA, an affiliate of Merck KGaA. GG is an employee of Merck Healthcare KGaA, Darmstadt, Germany. PTN has served in a consulting or advisory role for 4SC, Merck, MSD, Pfizer, and Sanofi/Regeneron; received travel and accommodations expenses from MSD and Sanofi/Regeneron; has a patent pending for high-affinity T-cell receptors that target the Merkel polyomavirus; and has received research funding from Bristol Myers Squibb and Merck. All other authors have declared no conflicts of interest. For all new products or new indications approved in both the European Union and the United States after 1 January 2014, Merck will share patient-level and study-level data after deidentification, as well as redacted study protocols and clinical study reports from clinical trials in patients. These data will be shared with qualified scientific and medical researchers, upon researcher's request, as necessary for conducting legitimate research. Such requests must be submitted in writing to the company's data sharing portal. More information can be found at https://www.merckgroup.com/en/research/our-approach-to-research-and-development/healthcare/clinical-trials/commitment-responsible-data-sharing.html. Where Merck has a co-research, co-development, or co-marketing/co-promotion agreement or where the product has been out-licensed, it is recognized that the responsibility for disclosure may be dependent on the agreement between parties. Under these circumstances, Merck will endeavor to gain agreement to share data in response to requests. The trial was conducted in accordance with the Declaration of Helsinki and the International Council for Harmonisation Good Clinical Practice Guidelines. The protocol was approved by the independent ethics committee or institutional review board at each participating center, and all patients provided written informed consent before enrollment.
