Efficacy, Safety, and Biomarker Analysis of Combined PD-L1 (Atezolizumab) and VEGF (Bevacizumab) Blockade in Advanced Malignant Peritoneal Mesothelioma

Kanwal Raghav(The University of Texas MD Anderson Cancer Center), Suyu Liu(The University of Texas MD Anderson Cancer Center), Michael J. Overman(The University of Texas MD Anderson Cancer Center), Anneleis F. Willett(The University of Texas MD Anderson Cancer Center), Mark Knafl(The University of Texas MD Anderson Cancer Center), Szu-Chin Fu(The University of Texas MD Anderson Cancer Center), Anaís Malpica(The University of Texas MD Anderson Cancer Center), Seema Prasad(The University of Texas MD Anderson Cancer Center), Richard E. Royal(The University of Texas MD Anderson Cancer Center), Christopher P. Scally(The University of Texas MD Anderson Cancer Center), Paul F. Mansfield(The University of Texas MD Anderson Cancer Center), Ignacio I. Wistuba(The University of Texas MD Anderson Cancer Center), P. Andrew Futreal(The University of Texas MD Anderson Cancer Center), Dipen M. Maru(The University of Texas MD Anderson Cancer Center), Luisa M. Solis Soto(The University of Texas MD Anderson Cancer Center), Edwin R. Parra(The University of Texas MD Anderson Cancer Center), Honglei Chen(The University of Texas MD Anderson Cancer Center), Pamela Villalobos(The University of Texas MD Anderson Cancer Center), Anuj Verma(The University of Texas MD Anderson Cancer Center), Armeen Mahvash(The University of Texas MD Anderson Cancer Center), Patrick Hwu(The University of Texas MD Anderson Cancer Center), Patricia Cortazar(Kaiser Permanente South San Francisco Medical Center), Edward McKenna(Kaiser Permanente South San Francisco Medical Center), Cindy Yun(Kaiser Permanente South San Francisco Medical Center), Shannon Dervin(Kaiser Permanente South San Francisco Medical Center), Katja Schulze(Kaiser Permanente South San Francisco Medical Center), Walter C. Darbonne(Kaiser Permanente South San Francisco Medical Center), Ajaykumar C. Morani(The University of Texas MD Anderson Cancer Center), Scott Kopetz(The University of Texas MD Anderson Cancer Center), Keith F. Fournier(The University of Texas MD Anderson Cancer Center), Scott E. Woodman(The University of Texas MD Anderson Cancer Center), James C. Yao(The University of Texas MD Anderson Cancer Center), Gauri R. Varadhachary(The University of Texas MD Anderson Cancer Center), Daniel M. Halperin(The University of Texas MD Anderson Cancer Center)
Cancer Discovery
July 14, 2021
10.1158/2159-8290.cd-21-0331
Cited by 72Open Access
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Abstract

Abstract Malignant peritoneal mesothelioma (MPeM) is a rare but aggressive malignancy with limited treatment options. VEGF inhibition enhances efficacy of immune-checkpoint inhibitors by reworking the immunosuppressive tumor milieu. Efficacy and safety of combined PD-L1 (atezolizumab) and VEGF (bevacizumab) blockade (AtezoBev) was assessed in 20 patients with advanced and unresectable MPeM with progression or intolerance to prior platinum–pemetrexed chemotherapy. The primary endpoint of confirmed objective response rate per RECISTv1.1 by independent radiology review was 40% [8/20; 95% confidence interval (CI), 19.1–64.0] with median response duration of 12.8 months. Six (75%) responses lasted for >10 months. Progression-free and overall survival at one year were 61% (95% CI, 35–80) and 85% (95% CI, 60–95), respectively. Responses occurred notwithstanding low tumor mutation burden and PD-L1 expression status. Baseline epithelial–mesenchymal transition gene expression correlated with therapeutic resistance/response (r = 0.80; P = 0.0010). AtezoBev showed promising and durable efficacy in patients with advanced MPeM with an acceptable safety profile, and these results address a grave unmet need for this orphan disease. Significance: Efficacy of atezolizumab and bevacizumab vis-à-vis response rates and survival in advanced peritoneal mesothelioma previously treated with chemotherapy surpassed outcomes expected with conventional therapies. Biomarker analyses uncovered epithelial–mesenchymal transition phenotype as an important resistance mechanism and showcase the value and feasibility of performing translationally driven clinical trials in rare tumors. See related commentary by Aldea et al., p. 2674. This article is highlighted in the In This Issue feature, p. 2659

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