New Drug Combination Shows Promise for Peritoneal Mesothelioma

Researchers at MD Anderson Cancer Center in Houston have uncovered a new, promising treatment option for patients with peritoneal mesothelioma, potentially filling a gaping void that exists today.

The immunotherapy drug combination of Tecentriq and Avastin, known generically as atezolizumab and bevacizumab, respectively, showed unusual efficacy in a recent study of 20 patients with this rare cancer.

Although some patients have previously found significant success and extended survival with the cytoreductive surgery and hyperthermic intraperitoneal chemotherapy combination, or HIPEC, those with unresectable disease have been left with no good options.

Until now, possibly.

The unique synergy between the study’s two drugs produced a safe and durable response with mesothelioma patients regardless of tumor mutational burden or biomarkers previously thought to predict effectiveness.

Cancer Discovery published the study July 14.

“The combination of bevacizumab and atezolizumab showed promising tumor shrinkage,” MD Anderson Cancer Center oncologist and lead study author Dr. Kanwal Raghav told The Mesothelioma Center at Asbestos.com. “This combination is a very good and reliable second-line option for patients.”

Efficacy of Drug Combination Impresses Researchers

According to the study, all participants started second-line treatment after experiencing disease progression following earlier standard chemotherapy, the aggressive surgical procedure or both.

The effectiveness was impressive.

Median duration of response was 12.8 months. Estimated progression-free survival was 17.6 months.  By comparison, patients receiving standard chemotherapy entered the study with median disease progression of 8.3 months.

“We were not surprised, but definitely impressed by the degree of activity,” Raghav said.

Median overall survival has not been reached, but the one-year survival rate was 85%. Progression-free survival at one year was 65%. Disease control was seen in 95% and 85% of patients at 12 and 18 weeks, respectively.

The study was part of a multicohort clinical trial at MD Anderson evaluating this drug combination in several rare, solid cancers, including appendiceal and pancreatic cancer and pleural mesothelioma, which is primarily caused by exposure to asbestos. Results from the other cancers have not yet been released.

Peritoneal mesothelioma patients received the drugs intravenously every 21 days until disease progression or unacceptable toxicity. Patients received a median of 15 cycles of treatment.

At the data cutoff of 23.5 months, six patients were still receiving treatment. There was treatment discontinuation for 10 participants because of disease progression, two due to toxicity, one by death and one by optional withdrawal.

All study participants at MD Anderson were enrolled between March 30, 2017, and Feb. 12, 2019.

“Patients treated on this regimen surpassed outcomes expected with conventional therapies,” Raghav said in an MD Anderson statement. “This data shows that this is a reasonable treatment option and reiterates the importance of clinical trials for rare cancers to extend patient survival.”

Two-Drug Synergy Is Key

Previously, both drugs have been tried individually in treating mesothelioma but lacked sustainability. Together, though, the synergy was dramatic.

Tecentriq is a type of immunotherapy drug known as an immune checkpoint inhibitor that targets a cell surface protein called PD-L1, which helps control the immune system but stops it from attacking cancer cells.

The way Tecentriq works is similar to Keytruda or Opdivo, which have received approvals for pleural mesothelioma treatment  – but not peritoneal mesothelioma – from the U.S. Food and Drug Administration. Tecentriq has been approved for certain non-small cell lung cancers and bladder cancers.

Avastin, known as an angiogenesis drug, is a different type of immunotherapy that works by inhibiting another specific protein and restricting the development of new blood vessels.

“The efficacy in our cohort is conceivably a result of complex synergistic interactions,” the authors wrote.

More Clinical Trials Needed

Study authors emphasized that a larger number of patients in additional clinical trials are needed to validate their study results and determine if the combination should be used as a first-line treatment.

“I am very encouraged by the responses to this treatment,” Raghav said. “There is a grave, unmet need for patients with peritoneal mesothelioma. We’re hopeful that with additional research, this will provide a better treatment option for these patients.”

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