1915P - Phase I trial of adjuvant pembrolizumab after radiation therapy for lung-intact malignant pleural mesothelioma

Background

This study assessed the safety of pembrolizumab after radiotherapy (RT) for patients with malignant pleural mesothelioma (MPM) who evaded extrapleural pneumonectomy.

Methods

Two cohorts were accrued and monitored for toxicity: one receiving extensive hemithoracic RT (Cohort 1), and the other receiving limited field palliative RT (Cohort 2). In Cohort 1, nonmetastatic patients received induction platinum/pemetrexed, then pleurectomy/decortication when feasible, followed by hemithoracic RT in 25 fractions. After RT, all patients received pembrolizumab at 200mg given every 3 weeks until progression, unacceptable toxicity, or 2 years. Primary endpoint was high-grade adverse events (AEs) monitored for 4 months after RT. Secondary endpoints included overall survival (OS) and progression-free survival (PFS) evaluated on imaging every 6 weeks for 2 years then every 12 weeks.

Results

Twenty-four patients were enrolled (12 per Cohort). Median follow-up was 15.5 months. Four patients came off study early within the post-treatment monitoring period (2 for AEs possibly related to treatment). Nine Grade 3 and one Grade 4 treatment-related AEs were recorded among 3 patients (12.5%): 2 (17%) in Cohort 1 vs. 1 (8%) in Cohort 2 (p=1.00). Grade 3 AEs included anorexia, dysphagia, dyspnea, esophagitis, gastritis, lymphopenia, mucositis, and pneumonitis. One Grade 4 lymphopenia occurred in Cohort 1. No treatment-related deaths were observed, though two unrelated deaths (1 in each cohort) occurred within 30 days. Median PFS was 5.9 months (95% CI: 4.2-9.8), demonstrating no significant difference between Cohort 1: 7.7 months (95% CI: 4.2-19.8) and Cohort 2: 4.0 months (95% CI: 3.3-11.4, log-rank p=0.336). Median OS was 14.6 months (95% CI: 9.8-20.7), with no significant difference between Cohort 1: 12.2 months (95% CI: 7.7-23.6) and Cohort 2: 16.3 months (95% CI: 6.3-22.2, log-rank p=0.697).

Conclusions

Pembrolizumab is well-tolerated after RT for MPM with acceptable safety profile. The study seems to suggest no difference in outcomes with extensive hemithoracic RT compared to limited-field palliative RT for lung-intact MPM.

Clinical trial identification

NCT02959463.

Editorial acknowledgement

Legal entity responsible for the study

UT MD Anderson Cancer Center.

Funding

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA provided drug and financial support for the study.

Disclosure

S.H.H. Lin: Financial Interests, Personal, Other, Consultant: XRAD Therapeutics; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Full or part-time Employment: The University of Texas MD Anderson Cancer Center; Financial Interests, Personal, Ownership Interest, Co-Founder and Scientific Advisor: Seek Diagnostics; Financial Interests, Personal, Research Grant: STCube Pharmaceuticals, Beyond Spring Pharmaceuticals; Financial Interests, Personal, Funding: Nektar Therapeutics. L.A. Byers: Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme Corp, Arrowhead, Chugai Pharmaceutical Co., Genentech Inc, AbbVie, Jazz Pharmaceuticals, Puma Biotechnology, Amgen, Daiichi Sanyo, BeiGene; Financial Interests, Personal, Advisory Board, Per our institutional policy compensation from any consulting/etc. would always be <25000 for any 12 month period: AstraZeneca Pharmaceuticals; Financial Interests, Institutional, Funding, Research funding: AstraZeneca Pharmaceuticals, Amgen. All other authors have declared no conflicts of interest.