Efficacy of nivolumab/ipilimumab as first-line treatment of pleural mesothelioma in the German real-world setting.

8085 Background: The approval of nivolumab/ipilimumab (IO) has extended the first-line treatment options in unresectable pleural mesothelioma (PM). In the Checkmate 743 trial, first-line IO treatment resulted in similar survival benefit for both non-epithelioid (NE) and epithelioid (E) subtype with median survival of 18 months. However, data about efficacy in unselected populations from the real-world setting are scarce. Methods: We retrospectively collected clinical data of patients (pts) with PM diagnosed between 2010-2023 from twelve centers in Germany and analyzed cases that received at least one cycle of IO in the first-line setting. Median progression-free (mPFS) and overall survival (mOS) were estimated using Kaplan-Meier method and compared using the log-rank method. All statistical analyses were conducted using R software (4.3.2). Results: Overall 1574 patients were collected, of which 931 received any first-line systemic treatment and 135 were treated with IO in the first-line. The latter were mostly male (85%), older than 65 years (78%), current or former smokers (54%), and had E histology (67%). Mean age was 72 (standard deviation SD 8.4) years. The ECOG PS score (PS) was ≥2 in 5 cases only, but not available in 23. Only 64/135 (47%) pts went on to receive any second-line treatment, i.e. platinum/pemetrexed in 47, monochemotherapy (pemetrexed, gemcitabine or vinorelbine) in 15, IO re-challenge in 1 and nivolumab in 1. With median follow-up of 9 months (IQR 4.8-14.5), the mOS for the entire cohort was 13.6 mo (95% confidence interval CI 10.64-17.35). By histology, the mOS in NE was 16.6 mo vs. 13.6 mo in E histology HR 0.89 (95%CI 0.54-1.48), p=0.65. The mOS difference in pts with PS 0 vs 1 vs. >=2 was 16.6 mo vs. 12.8 mo vs. 3.5 mo HR 1.45 (95% CI 0.90-2.36); p=0.13. 2/5 pts with PS ≥ 2 died within first 4 months. When age at diagnosis was considered, mOS in age group “< 65”, “≥ 65 to <75” and “≥75”-years were 18.8 mo, 16.6 mo, and 9.6 mo HR 1.37 (95%CI 1-1.88), p=0.047, respectively. The mOS in never (N=42) vs. current or past smokers (N=52) was 10 mo vs. 14 mo HR 0.67 (95%CI 0.39-1.14), p=0.14, respectively. The mPFS for the entire cohort was 4.76 mo (95% CI 3.7-6.7), 5.6 mo for the NE and 4.2 mo for E histology HR 0.77 (95% CI 0.51 -1.16); p=0.21. Subsequent treatment with Platin/Pemetrexed yielded a numerically longer mOS of 10 mo compared to 6.3 mo with monochemotherapy HR 1.96 (95%CI 0.88-4.3), p=0.09. Conclusions: In this real-world analysis of unselected patients, survival benefit with nivolumab/ipilimumab was somewhat less pronounced in both non-epithelioid and epithelioid subtypes compared to the Checkmate 743 trial. Older patients had worse prognosis, while there was also a tendency for shorter survival of never smokers and patients with worse ECOG performance status. Further analysis of larger real-world datasets with longer follow-up will be essential to validate these results.