Platinum/Pemetrexed Active in Mesothelioma After First-Line Immunotherapy
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A study of the German MesoNet cohort demonstrates that treating pleural mesothelioma with platinum plus pemetrexed after first-line nivolumab plus ipilimumab yields a median overall survival of 11.5 months.
According to results from a retrospective study of the German MesoNet cohort, published in Clinical Lung Cancer, second-line platinum plus pemetrexed produced a median overall survival (OS) of 11.5 months (95% CI, 8.6-13.8) and disease control in 72% of patients with pleural mesothelioma whose disease had progressed after first-line nivolumab (Opdivo) plus ipilimumab (Yervoy).
Among 135 patients treated with first-line nivolumab plus ipilimumab across the MesoNet cohort's 12 participating German cancer centers, 57 patients (42%) went on to receive second-line therapy, and 41 of those patients (72%) received platinum plus pemetrexed. Median progression-free survival (PFS) with the regimen was 5.8 months (95% CI, 4.1-7), and partial responses were observed in 28% of patients, contributing to the overall 72% disease control rate.
Study Design
Nivolumab plus ipilimumab has been a standard first-line option for unresectable pleural mesothelioma since its October 2020 FDA approval, based on the phase 3 CheckMate 743 trial (NCT02899299), which showed an OS benefit over platinum plus pemetrexed chemotherapy. No regimen carries formal approval for use after first-line immunotherapy fails, leaving clinicians to extrapolate second-line decisions largely from first-line efficacy data.
This retrospective, multicenter analysis drew on the MesoNet real-world cohort of patients with pleural mesothelioma treated across 12 cancer centers in Germany. The primary objective was to evaluate outcomes among patients who received second-line platinum plus pemetrexed after progressing on first-line nivolumab plus ipilimumab; a secondary objective was to characterize subsequent treatment patterns in the broader cohort. Investigators, led by Rajiv Shah, MD, of the Department of Thoracic Oncology at Thoraxklinik, Heidelberg University Hospital, and the National Center for Tumor Diseases Heidelberg, assessed radiologic response, OS, and PFS from the start of second-line treatment.
With a median OS of 11.5 months and median PFS of 5.8 months, second-line platinum plus pemetrexed showed clinical activity regardless of patients' response to prior immunotherapy, according to the study authors. Subtype analysis showed a trend toward longer median OS with nonepithelioid vs epithelioid histology (13 months vs 9.5 months). The authors noted that these findings support platinum plus pemetrexed as an active regimen in the post-immunotherapy setting, even though no second-line treatment currently carries formal approval for pleural mesothelioma.
Clinical Context and Limitations
No prospective trials have evaluated platinum plus pemetrexed specifically after first-line nivolumab plus ipilimumab, and current guideline recommendations for this sequence rely largely on efficacy data generated in the first-line setting, the study authors noted. The retrospective design, the real-world cohort's inherent selection for patients fit enough to receive second-line therapy, and the absence of a comparator arm limit conclusions about the regimen's added benefit beyond natural history. The authors concluded that the real-world activity observed supports platinum plus pemetrexed as an effective second-line option but that careful patient selection and earlier treatment initiation remain critical given the high rate of attrition.
