First-line avelumab in a cohort of 116 patients with metastatic Merkel cell carcinoma (JAVELIN Merkel 200)

• Verfasst von: D'Angelo, Sandra P. [VerfasserIn]
• Verfasst von: Lebbe, Celeste [VerfasserIn]
• Verfasst von: Mortier, Laurent [VerfasserIn]
• Verfasst von: Brohl, Andrew S. [VerfasserIn]
• Verfasst von: Fazio, Nicola [VerfasserIn]
• Verfasst von: Grob, Jean-Jacques [VerfasserIn]
• Verfasst von: Prinzi, Natalie [VerfasserIn]
• Verfasst von: Hanna, Glenn J. [VerfasserIn]
• Verfasst von: Hassel, Jessica C. [VerfasserIn]
• Verfasst von: Kiecker, Felix [VerfasserIn]
• Verfasst von: Georges, Sara [VerfasserIn]
• Verfasst von: Ellers-Lenz, Barbara [VerfasserIn]
• Verfasst von: Shah, Parantu [VerfasserIn]
• Verfasst von: Guezel, Gulseren [VerfasserIn]
• Verfasst von: Nghiem, Paul [VerfasserIn]
• Titel: First-line avelumab in a cohort of 116 patients with metastatic Merkel cell carcinoma (JAVELIN Merkel 200)
• Titelzusatz: primary and biomarker analyses of a phase II study
• Verf.angabe: Sandra P. D'Angelo, Celeste Lebbe, Laurent Mortier, Andrew S. Brohl, Nicola Fazio, Jean-Jacques Grob, Natalie Prinzi, Glenn J. Hanna, Jessica C. Hassel, Felix Kiecker, Sara Georges, Barbara Ellers-Lenz, Parantu Shah, Gulseren Guezel, Paul Nghiem
• Jahr: 2021
• Umfang: 10 S.
• Fussnoten: Gesehen am 24.01.2022
• Titel Quelle: Enthalten in: Journal for ImmunoTherapy of Cancer
• Ort Quelle: London : BioMed Central, 2013
• Jahr Quelle: 2021
• Band/Heft Quelle: 9(2021), 7, Artikel-ID e002646, Seite 1-10
• ISSN Quelle: 2051-1426
• DOI: doi:10.1136/jitc-2021-002646
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: chemotherapy
• Sach-SW: clinical trials
• Sach-SW: gene expression profiling
• Sach-SW: immunotherapy
• Sach-SW: independent predictor
• Sach-SW: outcomes
• Sach-SW: phase II as topic
• Sach-SW: profile
• Sach-SW: safety
• Sach-SW: skin neoplasms
• Sach-SW: tumor
• Sach-SW: tumor biomarkers
• K10plus-PPN: 178698492X

Abstract

Background Avelumab (anti-programmed death ligand 1 (PD-L1)) is approved in multiple countries for the treatment of metastatic Merkel cell carcinoma (mMCC), a rare and aggressive skin cancer. We report efficacy and safety data and exploratory biomarker analyses from a cohort of patients with mMCC treated with first-line avelumab in a phase II trial. Methods Patients with treatment-naive mMCC received avelumab 10 mg/kg intravenously every 2 weeks. The primary endpoint was durable response, defined as objective response (complete or partial response; assessed by independent review) lasting >= 6 months. Additional assessments included progression-free survival (PFS), overall survival (OS), safety, and biomarker analyses. Results In 116 patients treated with avelumab, median follow-up was 21.2 months (range: 14.9-36.6). Thirty-five patients had a response lasting >= 6 months, giving a durable response rate of 30.2% (95% CI: 22.0% to 39.4%). The objective response rate was 39.7% (95% CI: 30.7% to 49.2%). Median PFS was 4.1 months (95% CI: 1.4 to 6.1) and median OS was 20.3 months (95% CI: 12.4 to not estimable). Response rates were numerically higher in patients with PD-L1+ tumors, Merkel cell polyomavirus (MCPyV)-negative tumors, and tumors with increased intratumoral CD8(+) T-cell density. Exploratory analyses did not identify a biomarker that could reliably predict a response to first-line treatment with avelumab; however, a novel gene expression signature to identify the presence of MCPyV+ tumors was derived. Treatment-related adverse events (any grade) occurred in 94 (81.0%) patients, including grade 3/4 events in 21 (18.1%) patients; no treatment-related deaths occurred. Conclusion In patients with mMCC, first-line treatment with avelumab led to responses in 40% and durable responses in 30%, and was associated with a low rate of grade 3/4 treatment-related adverse events.