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

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.

SUBMITTER: Raghav K 

PROVIDER: S-EPMC8563380 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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

Raghav Kanwal K   Liu Suyu S   Overman Michael J MJ   Willett Anneleis F AF   Knafl Mark M   Fu Szu-Chin SC   Malpica Anais A   Prasad Seema S   Royal Richard E RE   Scally Christopher P CP   Mansfield Paul F PF   Wistuba Ignacio I II   Futreal Andrew P AP   Maru Dipen M DM   Solis Soto Luisa M LM   Parra Cuentas Edwin R ER   Chen Honglei H   Villalobos Pamela P   Verma Anuj A   Mahvash Armeen A   Hwu Patrick P   Cortazar Patricia P   McKenna Edward E   Yun Cindy C   Dervin Shannon S   Schulze Katja K   Darbonne Walter C WC   Morani Ajaykumar C AC   Kopetz Scott S   Fournier Keith F KF   Woodman Scott E SE   Yao James C JC   Varadhachary Gauri R GR   Halperin Daniel M DM  

Cancer discovery 20210714 11

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 objecti  ...[more]

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