乌鸦传媒

A combination of atezolizumab (Tecentriq) and bevacizumab appeared effective and safe in patients with advanced malignant peritoneal mesothelioma, according to results from a small single-arm trial.

The combination achieved an objective response rate (ORR) of 40% in patients who had progressed on or were resistant to prior platinum-pemetrexed (Alimta) chemotherapy, reported Kanwal Raghav, MD, of MD Anderson Cancer Center in Houston, and colleagues in .

The responses were "robust and durable ... with meaningful prolongation of survival," the team wrote.

"There is absolutely no other therapy approved for use in this setting," Raghav told 乌鸦传媒. "The only treatments we use are cytotoxic chemotherapies, like gemcitabine, all of which have response rates of less than 10%."

Malignant peritoneal mesothelioma is an aggressive, although extremely rare (only about 275 new cases per year in the U.S.), malignancy that has few treatment options.

Therapy for the disease is largely based on data extrapolated from studies of pleural mesothelioma, Raghav explained. "But there are many differences between these diseases. Epidemiologically speaking, pleural mesothelioma is associated with lots of asbestos exposure, but peritoneal mesothelioma might not be. And peritoneal mesothelioma is more common in women than men and is diagnosed at an earlier age and more often with advanced disease."

He noted that National Comprehensive Cancer Network guidelines recommend first-line platinum-pemetrexed chemotherapy for both types of mesothelioma, "but after failure of this first-line therapy there is no recommended standard or FDA-approved therapy for advanced [malignant peritoneal mesothelioma], and a critical unmet need of novel therapies for this novel disease exists."

Atezolizumab, an immune checkpoint inhibitor, targets PD-L1, while bevacizumab is a targeted therapy that inhibits vascular endothelial growth factor (VEGF). The combination has been shown effective in advanced hepatocellular carcinoma and is FDA approved for that indication in first-line.

"Our hypothesis was that the disease is immunologically active, but there is a VEGF axis that is suppressing the immune system and if we inhibit the VEGF axis and bring in the immune checkpoint inhibitor, we might be able to get better responses, just like what has been seen with hepatocellular carcinoma," Raghav said.

The study included 20 patients; median age was 63, 12 were women, and 15 self-reported that they had not been exposed to asbestos.

Atezolizumab was administered at a fixed dose of 1,200 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 the study was ORR per Response Evaluation Criteria in Solid Tumors v.1.1 by independent radiology review. In addition to the finding of an ORR of 40%, when patients responded, "they responded for a long time," Raghav said.

The median duration of response was 12.8 months, and of the eight patients who responded, six had responses that lasted for at least 10 months -- "which is unprecedented for this disease, and we still have patients in this study who have been on this treatment for over 2 years and they are still doing great," Raghav said.

The 1-year, progression-free survival rate was 61%, and overall survival was 85%.

Treatment-related adverse events (TRAEs) of any grade were reported in 85% of patients, the researchers reported. Grade 3 TRAEs occurred in 10 patients, the most common of which were hypertension and anemia. Two patients had grade 3 immune-related AEs (pancreatitis and proteinuria) that were managed with corticosteroids and required treatment discontinuation.

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