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Real-world analysis of a drug combination for malignant peritoneal mesothelioma

A recent phase II study used real-world evidence to assess responses to a combination treatment of atezolizumab and bevacizumab in patients with advanced malignant peritoneal mesothelioma, a rare cancer in the lining of the abdomen.

Malignant peritoneal mesothelioma

Malignant peritoneal mesothelioma (MPeM) is a rare, lethal cancer with a 5-year survival rate lower than 20%. MPeM arises from mesothelial cells that line the serosal layer of the peritoneum. The condition typically presents with abdominal discomfort, distension and ascites. In contrast with its more common analogue malignant pleural mesothelioma (MPM), MPeM is far less frequent, with an estimated 2,458 new cases per year in the US, compared with 275 new MPM cases per year.

MPeM has a weaker association with asbestos exposure, affects women more frequently, occurs at a younger age and is diagnosed more often in advanced stages of disease compared with MPM. Moreover, MPeM and MPM have been identified as molecularly dissimilar, with copy number gains and BAP1 mutations more common in MPeM.

Treatments for malignant peritoneal mesothelioma

MPeM treatment strategies vary by patient and disease factor. Optimal cytoreductive surgery (CRS), hyperthermic intraoperative peritoneal perfusion with chemotherapy (HIPEC) and early postoperative intraperitoneal chemotherapy (EPIC) can result in good outcomes for select patients. However, a substantial proportion of these patients still require systemic therapy and have limited survival. Despite the recognised clinico-molecular and epidemiological differences, systemic therapy for MPeM is largely based on data extrapolated from MPM or scant retrospective/prospective evidence. Therefore, a consensus regarding optimal treatments for MPeM is lacking.

The National Comprehensive Cancer Network (NCCN) previously recommended first-line platinum chemotherapy for both MPM and MPeM. However, after disease progression there is no established treatment strategy or any FDA-approved treatments for advanced MPeM.

Evaluation of drug combination for advanced MPeM treatment

In this single-centre study, the team conducted a multicohort basket trial to evaluate the effectiveness of atezolizumab and bevacizumab in a variety of advanced cancers. The combined treatment with these drugs is commonly known as AtezoBev. Atezolizumab is an immune checkpoint inhibitor that targets PD-L1. Meanwhile, bevacizumab is a targeted therapy that slows the growth factor – VEGF.

Since historical data regarding MPeM is scarce, the researchers leveraged real-world evidence to evidence any benefits identified from AtezoBev treatment. The study reported data from 20 patients included in the MPeM cohort, for which the median age was 63 years, 60% of the participants were women and 75% reported that they had not been exposed to asbestos. Additionally, trial participants were 80% white, 10% Hispanic, 5% black and 5% other.

Prior to enrolling in this trial, patients who received standard of care chemotherapy progressed to next treatment at 8.3 months, compared to 17.6 months with AtezoBev on the study. Overall, the median response duration was 12.8 months.

Progression-free and overall survival at one year were 61% and 85%, respectively. It was found that the treatment was well-tolerated, with the most common adverse events being hypertension and anaemia. The lead researcher on this study, Associate Professor Kanwal Raghav, said that ‘patients treated on this regiment surpassed outcomes expected with conventional therapies’. Moreover, Raghav states that ‘this data shows that this is a reasonable treatment option and reiterates the importance of clinical trials for rare cancers to extend patient survival’.

Summary

This study evaluated the effectiveness of a drug combination treatment consisting of atezolizumab and bevacizumab in patients with advanced malignant peritoneal mesothelioma. It was found that AtezoBev treatment improved progression-free and overall survival rates and the treatment regimen was well tolerated in the trial participants. However, additional trials with larger patient numbers are needed to validate these study results to determine if this drug combination could be given as a frontline treatment or to improve surgical outcomes.

Image credit: kjpargeter – Freepik

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