Platinum/Pemetrexed Active in Mesothelioma After First-Line Immunotherapy

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).¹

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.² 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.¹ 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.

Efficacy Outcomes

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.

Treatment Attrition Underscores Early Planning

Investigators also highlighted substantial attrition across lines of therapy. Of the 135 patients who began first-line nivolumab plus ipilimumab, 58% never went on to receive second-line treatment, and only 22 patients (16% of the original cohort) went on to receive third-line therapy. The study authors said this pattern points to the need for early consideration of second-line treatment while patients remain fit, cautioning that delaying the decision risks disease progression or physical decline that can foreclose further therapy.

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.

REFERENCES

1. Shah R, Buchmeier EL, Kopp HG, et al. Outcomes of platinum plus pemetrexed and treatment patterns following first-line nivolumab and ipilimumab in pleural mesothelioma: real-world results from the German MesoNet study. Clin Lung Cancer. 2026;27(6):68-74. doi:10.1016/j.cllc.2026.06.001

2. Baas P, Scherpereel A, Nowak AK, et al. First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial. Lancet. 2021;397(10272):375-386. doi:10.1016/S0140-6736(20)32714-8