Glutsch, Valerie and Schummer, Patrick and Kneitz, Hermann and Gesierich, Anja and Goebeler, Matthias and Klein, Detlef and Posch, Christian and Gebhardt, Christoffer and Haferkamp, Sebastian and Zimmer, Lisa and Becker, Juergen C. and Leiter, Ulrike and Weichenthal, Michael and Schadendorf, Dirk and Ugurel, Selma and Schilling, Bastian (2022) Ipilimumab plus nivolumab in avelumab-refractory Merkel cell carcinoma: a multicenter study of the prospective skin cancer registry ADOREG. JOURNAL FOR IMMUNOTHERAPY OF CANCER, 10 (11): e005930. ISSN , 2051-1426
Full text not available from this repository. (Request a copy)Abstract
Merkel cell carcinoma is a rare, highly aggressive skin cancer with neuroendocrine differentiation. Immune checkpoint inhibition has significantly improved treatment outcomes in metastatic disease with response rates to programmed cell death protein 1/programmed cell death 1 ligand 1 (PD-1/PD-L1) inhibition of up to 62%. However, primary and secondary resistance to PD-1/PD-L1 inhibition remains a so far unsolved clinical challenge since effective and safe treatment options for these patients are lacking.Fourteen patients with advanced (non-resectable stage III or stage IV, Union international contre le cancer 2017) Merkel cell carcinoma with primary resistance to the PD-L1 inhibitor avelumab receiving subsequent therapy (second or later line) with ipilimumab plus nivolumab (IPI/NIVO) were identified in the prospective multicenter skin cancer registry ADOREG. Five of these 14 patients were reported previously and were included in this analysis with additional follow-up. Overall response rate, progression-free survival (PFS), overall survival (OS) and adverse events were analyzed.All 14 patients received avelumab as first-line treatment. Thereof, 12 patients had shown primary resistance with progressive disease in the first tumor assessment, while two patients had initially experienced a short-lived stabilization (stable disease). Six patients had at least one systemic treatment in between avelumab and IPI/NIVO. In total, 7 patients responded to IPI/NIVO (overall response rate 50%), and response was ongoing in 4 responders at last follow-up. After a median follow-up of 18.85 months, median PFS was 5.07 months (95% CI 2.43-not available (NA)), and median OS was not reached. PFS rates at 12 months and 24 months were 42.9% and 26.8 %, respectively. The OS rate at 36 months was 64.3%. Only 3 (21%) patients did not receive all 4 cycles of IPI/NIVO due to immune-related adverse events.In this multicenter evaluation, we observed high response rates, a durable benefit and promising OS rates after treatment with later-line combined IPI/NIVO. In conclusion, our patient cohort supports our prior findings with an encouraging activity of second-line or later-line IPI/NIVO in patients with anti-PD-L1-refractory Merkel cell carcinoma.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | OPEN-LABEL; POLYOMAVIRUS; BLOCKADE; Skin Neoplasms; CTLA-4 Antigen; Programmed Cell Death 1 Receptor; B7-H1 Antigen; Drug Therapy; Combination |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Dermatologie und Venerologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 01 Feb 2024 08:11 |
| Last Modified: | 01 Feb 2024 08:11 |
| URI: | https://pred.uni-regensburg.de/id/eprint/58470 |
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