Outcomes of Platinum plus Pemetrexed Rechallenge in Pleural Mesothelioma: The Role of Platinum-Free Interval in a Multicenter Real-World Analysis
Year: 2026
Type: article
Study design: Observational Study
Abstract: Background Real-world (rw) use of rechallenge with platinum/pemetrexed (PP) in pleural mesothelioma (PM) has been recommended in international guidelines, but evidence is scarce and based on few very small retrospective studies. Methods 612 patients with PM treated with first-line PP between 2010 and 2023 across twelve centers were retrospectively identified. Outcomes and treatment patterns were analyzed across second-line regimens with particular focus on PP rechallenge. Platinum-free interval (PFI) was examined using a two-tier classification (platinum-sensitive ≥6 months, platinum-resistant <6 months) as a selection criterion. Results Among 375 patients (61%) receiving second-line therapy, median overall survival (OS) and rw progression-free survival (rwPFS) were 11.6 months and 4.7 months, respectively. Patients with PP rechallenge (n=78) showed a median OS of 20.5 months, median rwPFS of 6.8 months, and disease control rate (DCR) of 88%. Platinum-sensitive patients derived greater benefit from rechallenge, with OS differing across PFI categories (platinum-sensitive 21.4 months vs. platinum-resistant 11.9 months; p=0.007). Outcomes with Nivolumab/ipilimumab (n=29) were comparable to those observed with PP rechallenge (median OS 22.8 months, median rwPFS 8.0 months), with TFI (treatment-free interval) showing improved median OS in platinum-sensitive compared to platinum-resistant group (32 months vs. 18.1 months, p=0.03). Single-agent pemetrexed (n=32) and single-agent chemotherapy were associated with substantially shorter median OS of 11.6 and 8.0 months, respectively. Conclusion PP rechallenge demonstrated favorable outcomes and remains viable alternative in platinum-sensitive patients with PM, while nivolumab/ipilimumab may be considered in both TFI categories, particularly in platinum-resistant disease where PP rechallenge offers limited benefit. A PFI/TFI-guided approach to second-line treatment selection is supported, though prospective validation is warranted.
Authors: Rajiv Shah, Martin Reck, Christian Grohé, Martin Faehling, Daniel C. Christoph, Felix C. Saalfeld, Eva L. Buchmeier, Hans-Georg Kopp, Petra Hoffknecht, Nikolaj Frost, Frank Griesinger, Jonas Kuon, Jingting Luan, Julia Roeper, Martin Kimmich, Till Olchers, Paolo Chesi, Laura V. Klotz, Inn Chung, Helge Bischoff, Michael Thomas, Petros Christopoulos
Institutions: German Cancer Research Center, University Hospital Heidelberg, National Center for Tumor Diseases, German Center for Lung Research, LungenClinic Grosshansdorf, Evangelische Lungenklinik Berlin, Klinikum Esslingen, Ruhr University Bochum, Helmholtz-Zentrum Dresden-Rossendorf, University Hospital Carl Gustav Carus, Nationales Centrum für Tumorerkrankungen Dresden, Technische Universität Dresden, Kliniken der Stadt Köln, Humboldt-Universität zu Berlin, Freie Universität Berlin, Charité – Universitätsmedizin Berlin, Pius Hospital Oldenburg, Klinik Bad Bergzabern, Istituto Dermopatico dell'Immacolata, Istituti di Ricovero e Cura a Carattere Scientifico
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,000
Funder: Bristol-Myers Squibb
OpenAlex ID: W7204800774