Abstract 1915P
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.
Resources from the same session
1465P - Potential impact of APC mutation on survival via immune evasion through WNT signaling activation in HER2-positive gastric cancer treated with trastuzumab (tmab), nivolumab (nivo), and chemotherapy
Presenter: Takeru Wakatsuki
Session: Poster session 18
1468P - cGAS-driven inflammation in chromosomally unstable oesophagogastric adenocarcinoma
Presenter: Eileen Parkes
Session: Poster session 18
1469P - Development of an efficacy prediction model for concurrent chemoradiotherapy in esophageal squamous cell carcinoma using deep learning and multimodal data integration
Presenter: Xin Yang
Session: Poster session 18
1470TiP - Phase I trial of intraperitoneal infusion of GAIA-102 of NK-Like CD3-negative cells for gastric/pancreatic cancer
Presenter: Eiji Oki
Session: Poster session 18
1471TiP - MK-2870-015: A phase III study of trophoblast antigen 2 (TROP2)-directed antibody-drug conjugate (ADC) sacituzumab tirumotecan (sac-TMT) vs treatment of physician’s choice (TPC) for previously treated metastatic gastroesophageal adenocarcinoma (GEA)
Presenter: Zev Wainberg
Session: Poster session 18
1472TiP - Organ preservation with durvalumab-based immunotherapy in combination with chemoradiation as definitive therapy for early stage, cT1 and cT2N0, esophageal adenocarcinoma: A prospective, multicenter study of the FLOT-AIO Gastric Cancer Group – The IKF-057/ PRESTO trial
Presenter: Nils Homann
Session: Poster session 18
1473TiP - Neoadjuvant SOX combined with cadonilimab (AK104) for PD-L1 negative upper GC/GEJC patients
Presenter: Zhen Yuan
Session: Poster session 18
1474TiP - A randomized phase II study of disitamab vedotin (DV) plus toripalimab and chemotherapy versus DV plus toripalimab versus chemotherapy as perioperative treatment for HER2-expressing locally advanced gastric or gastroesophageal junction adenocarcinoma (GC/GEJ)
Presenter: Ziyu Li
Session: Poster session 18