The combination of PD-L1 and VEGF blockade demonstrated durable efficacy in patients with malignant peritoneal mesothelioma (MPeM), according to results of a phase 2 study published in Cancer Discovery.
The researchers indicated that the combination treatment with atezolizumab and bevacizumab was well-tolerated and led to robust and durable responses in patients with MPeM, addressing “a grave unmet need for this orphan disease.”
Although select patients have experienced success with optimal cytoreductive surgery and hyperthermic intraoperative peritoneal perfusion with chemotherapy, a significant proportion of patients with MPeM need systemic therapy and have limited survival.
The National Comprehensive Cancer Network recommends first-line platinum-pemetrexed chemotherapy for this rare life-threatening malignancy. However, there is no approved therapy after first-line therapy failure, pointing to a critical unmet need for patients with MPeM.
Investigators from the University of Texas MD Anderson Cancer Center designed a multicohort basket trial to evaluate atezolizumab plus bevacizumab in a variety of advanced rare cancers including MPeM.
The MPeM component of the phase 2 trial (ClinicalTrials.gov Identifier: NCT03074513) included 20 patients with unresectable and advanced MPeM who had disease progression or intolerance to first-line platinum-pemetrexed chemotherapy. The MPeM cohort had a median age of 63 years. A majority of these patients self-reported no prior asbestos exposure and 60% of the patients were women.
Patients received atezolizumab at a fixed dose of 1200 mg in combination with bevacizumab at a dose of 15 mg/kg intravenously every 21 days until disease progression or unacceptable toxicity.
The primary endpoint of confirmed objective response rate was achieved in 8 of 20 patients (40%; 95% CI, 19.1-64.0), with a median response duration of 12.8 months. Of the 8 responders, 6 had responses that lasted for more than 10 months. The patients had durable responses to the combination treatment regardless of response characteristics on prior chemotherapy.
The median follow-up was 23.5 months. The median progression-free survival (PFS) was 17.6 months (95% CI, 9.1-not reached). The 1-year PFS rate was 61% (95% CI, 35-80).
At the data cutoff, the median overall survival (OS) was not reached, and the 1-year OS was 85% (95% CI, 60-95). Responses were noted despite low tumor mutational burden and PD-L1 expression.
Treatment-related adverse events (AEs) were reported in 17 (85%) patients. Hypertension and anemia were the most common grade 3 AEs and occurred in 10 (50%) patients. There were no grade 4 or 5 AEs reported.
Transcriptomic profiling showed a correlation between baseline epithelial-mesenchymal transition (EMT) gene expression and the degree of therapeutic resistance or response to the combination of atezolizumab and bevacizumab (r=0.80; P =.0010). A high EMT gene expression score correlated with poor overall response rates.
“This study establishes a promising treatment option for our patients who suffer from this morbid cancer and represents an unprecedented effort to bridge the gap of dedicated research in this orphan disease,” the study authors wrote.
Disclosures: This research was partly supported by F Hoffmann-La Roche/Genentech. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Raghav K, Liu S, Overman MJ, et al. Efficacy, safety and biomarker analysis of combined PD-L1 (atezolizumab) and VEGF (bevacizumab) blockade in advanced malignant peritoneal mesothelioma. Cancer Discov. Published online July 14, 2021. doi:10.1158/2159-8290.CD-21-0331