Outcomes of Platinum plus /Pemetrexed Rechallenge in Pleural Mesothelioma: The Role of Platinum-Free Interval in a Multicenter Real-World Analysis.
14 affiliations
- 1Department of Thoracic Oncology, Thoraxklinik, Heidelberg University Hospital and National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and Heidelberg University Hospital, Germany; Translational Lung Research Center Heidelber, Member of the German Center for Lung Research, Heidelberg, Germany.
- 2Lung Clinic Grosshansdorf, Airway Research Center North, German Center for Lung Research (DZL), Grosshansdorf, Germany.
- 3Klinik für Pneumologie -Evangelische Lungenklinik Berlin Buch, Berlin, Germany.
- 4Department of Pneumology, Klinikum Esslingen GmbH, Esslingen, Germany.
- 5Thoraxzentrum Ruhrgebiet, Klinik für Pneumologie und Infektiologie, Sektion Thoraxonkologie, Ev. Krankenhaus Herne, Akad. Lehrkrankrankenhaus Ruhr-Universität Bochum, Herne, Germany.
- 6Department of Medicine I, University Hospital Carl Gustav Carus and NCT/UCC Dresden, a partnership between DKFZ, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, and Helmholtz-Zentrum Dresden-Rossendorf, Germany.
- 7Klinikum der Stadt Köln gGmbH, Cologne, Germany.
- 8Robert Bosch Centrum für Tumorerkrankungen, Klinik Schillerhöhe, Stuttgart, Germany.
- 9Franziskus Hospital Harderberg, Niels-Stensen-Kliniken, Department of Thoracic Oncology, Georgsmarienhütte, Germany.
- 10Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
- 11Department of Hematology and Oncology, University Department Internal Medicine-Oncology, Pius-Hospital, University Medicine Oldenburg, Oldenburg, Germany; PIUS Hospital Oldenburg, Universitätsklinik für Innere Medizin-Onkologie, Oldenburg, Germany.
- 12SLK Fachklinik Löwenstein, Löwenstein, Germany.
- 13Department of Oncology and Dermatological Oncology, IDI-IRCCS, Rome, Italy.
- 14Department of Thoracic Surgery, Thoraxklinik, Heidelberg University Hospital and NCT, NCT Heidelberg, a partnership between DKFZ and Heidelberg University Hospital, Germany; Translational Lung Research Center Heidelberg, Member of the DZL, Heidelberg, Germany.
Abstract
Real-world (rw) practice of rechallenge with platinum plus pemetrexed (PP) in pleural mesothelioma (PM) has been recommended in international guidelines, but the evidence is scarce and based on a few very small retrospective studies. In total, 612 patients with PM treated with first-line PP between 2010 and 2023 across 12 centers were retrospectively identified. Outcomes and treatment patterns were analyzed across second-line regimens, with a particular focus on PP rechallenge. The platinum-free interval (PFI) was evaluated using a two-tier classification (platinum-sensitive ≥6 mo and platinum-resistant <6 mo) as a selection criterion. Among 375 patients (61%) receiving second-line therapy, the rw median overall survival (rw-mOS) and rw median progression-free survival (rw-mPFS) were 11.6 months and 4.7 months, respectively. Patients with PP rechallenge (n = 78) had a median OS of 20.5 months, a median rwPFS of 6.8 months, and a disease control rate of 88%. Patients with platinum sensitivity derived greater benefit from rechallenge, with rw-mOS differing across PFI categories (platinum-sensitive: 21.4 mo versus platinum-resistant: 11.9 mo; p = 0.007). Outcomes with nivolumab plus ipilimumab (n = 29) were comparable to those observed with PP rechallenge (rw-mOS = 22.8 mo, rw-mPFS = 8.0 mo), with treatment-free interval (TFI) associated with improved median OS in the platinum-sensitive group compared with the platinum-resistant group (32 mo versus 18.1 mo, p = 0.03). Single-agent pemetrexed (n = 32) and single-agent chemotherapy were associated with substantially shorter rw-mOS of 11.6 and 8.0 months, respectively. In conclusion, PP rechallenge has favorable outcomes and remains a viable alternative in patients with platinum sensitivity with PM, whereas nivolumab plus ipilimumab may be considered in both TFI categories, particularly in platinum-resistant disease, in which PP rechallenge offers limited benefit. A PFI or TFI-guided approach to second-line treatment selection is supported, although prospective validation is warranted.
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BibTeX
@article{shah2026outcomes,
title = {{Outcomes of Platinum plus /Pemetrexed Rechallenge in Pleural Mesothelioma: The Role of Platinum-Free Interval in a Multicenter Real-World Analysis.}},
author = {Rajiv Shah and Martin Reck and Christian Grohé and Martin Faehling and Daniel C Christoph and Felix C Saalfeld and Eva L Buchmeier and Hans-Georg Kopp and Petra Hoffknecht and Nikolaj Frost and Frank Griesinger and Jonas Kuon and Jingting Luan and Julia Roeper and Martin Kimmich and Till Olchers and Paolo Chesi and Laura V Klotz and Inn Chung and Helge Bischoff and Michael Thomas and Petros Christopoulos},
journal = {JTO clinical and research reports},
year = {2026},
month = aug,
doi = {10.1016/j.jtocrr.2026.101073},
url = {https://europepmc.org/article/MED/42997725},
note = {CC BY},
}
RIS
TY - JOUR
TI - Outcomes of Platinum plus /Pemetrexed Rechallenge in Pleural Mesothelioma: The Role of Platinum-Free Interval in a Multicenter Real-World Analysis.
AU - Rajiv Shah
AU - Martin Reck
AU - Christian Grohé
AU - Martin Faehling
AU - Daniel C Christoph
AU - Felix C Saalfeld
AU - Eva L Buchmeier
AU - Hans-Georg Kopp
AU - Petra Hoffknecht
AU - Nikolaj Frost
AU - Frank Griesinger
AU - Jonas Kuon
AU - Jingting Luan
AU - Julia Roeper
AU - Martin Kimmich
AU - Till Olchers
AU - Paolo Chesi
AU - Laura V Klotz
AU - Inn Chung
AU - Helge Bischoff
AU - Michael Thomas
AU - Petros Christopoulos
PY - 2026
DA - 2026/08/31
JO - JTO clinical and research reports
DO - 10.1016/j.jtocrr.2026.101073
UR - https://europepmc.org/article/MED/42997725
AB - Real-world (rw) practice of rechallenge with platinum plus pemetrexed (PP) in pleural mesothelioma (PM) has been recommended in international guidelines, but the evidence is scarce and based on a few very small retrospective studies. In total, 612 patients with PM treated with first-line PP between 2010 and 2023 across 12 centers were retrospectively identified. Outcomes and treatment patterns were analyzed across second-line regimens, with a particular focus on PP rechallenge. The platinum-free interval (PFI) was evaluated using a two-tier classification (platinum-sensitive ≥6 mo and platinum-resistant <6 mo) as a selection criterion. Among 375 patients (61%) receiving second-line therapy, the rw median overall survival (rw-mOS) and rw median progression-free survival (rw-mPFS) were 11.6 months and 4.7 months, respectively. Patients with PP rechallenge (n = 78) had a median OS of 20.5 months, a median rwPFS of 6.8 months, and a disease control rate of 88%. Patients with platinum sensitivity derived greater benefit from rechallenge, with rw-mOS differing across PFI categories (platinum-sensitive: 21.4 mo versus platinum-resistant: 11.9 mo; p = 0.007). Outcomes with nivolumab plus ipilimumab (n = 29) were comparable to those observed with PP rechallenge (rw-mOS = 22.8 mo, rw-mPFS = 8.0 mo), with treatment-free interval (TFI) associated with improved median OS in the platinum-sensitive group compared with the platinum-resistant group (32 mo versus 18.1 mo, p = 0.03). Single-agent pemetrexed (n = 32) and single-agent chemotherapy were associated with substantially shorter rw-mOS of 11.6 and 8.0 months, respectively. In conclusion, PP rechallenge has favorable outcomes and remains a viable alternative in patients with platinum sensitivity with PM, whereas nivolumab plus ipilimumab may be considered in both TFI categories, particularly in platinum-resistant disease, in which PP rechallenge offers limited benefit. A PFI or TFI-guided approach to second-line treatment selection is supported, although prospective validation is warranted.
SN - 2666-3643
ER -