Oncologists throughout France have joined the U.S.-based National Comprehensive Cancer Network (NCCN) in upgrading their recommended standard-of-care treatment regimen for unresectable pleural mesothelioma.
Both groups have added bevacizumab (Avastin) to the traditional cisplatin and pemetrexed chemotherapy combination, expecting to see longer patient survival.
“This is a major advancement for the care of mesothelioma patients,” Dr. Gerard Zalcman, head of thoracic oncology at Bichat-Claude Bernard Hospital, told Asbestos.com. “Clearly, this drug can change the natural history of this tumor.”
Bevacizumab is known as an angiogenesis drug. It works by inhibiting a specific protein that stimulates the formation of new blood vessels in tumors, effectively slowing the growth of cancer cells. Bevacizumab works best in combination with chemotherapy.
A recent phase III clinical trial — led by The French Cooperative Thoracic Intergroup — showed an almost three-month improvement in median overall survival and progression-free survival for those receiving bevacizumab.
The trial was part of a study review published recently by Future Oncology and co-authored by Zalcman.
The NCCN, which includes almost 30 leading cancer centers in the U.S., offers guidelines to assist oncologists in making treatment decisions.
These guidelines often serve as a precursor to approval changes from the U.S. Food and Drug Administration (FDA), which hasn’t changed the cisplatin and pemetrexed standard-of-care regimen since 2004.
Zalcman believes the high cost of bevacizumab — $8,000-$10,000 monthly — has restricted its use outside the U.S. and France and will slow approval by the FDA.
He believes nintedanib, another angiogenesis inhibitor drug, likely will see FDA approval first because of projected lower costs.
The efficacy of nintedanib is still being studied in a phase III trial, but early results have been encouraging and showed even better survival times than bevacizumab.
Nintedanib, also known by brand name Ofev, already has FDA approval for pulmonary fibrosis. Oncologists in Europe are using it to treat certain lung cancer patients.
The lack of progress in pleural mesothelioma treatment has been a continued frustration for many oncologists.
Less than a third of those diagnosed with pleural mesothelioma are eligible for aggressive surgery.
According to the recent review, median overall survival is just 8-14 months for advanced disease, which includes the majority of patients, and 12-36 months for those with localized tumors.
The FDA first approved bevacizumab in 2004 to treat metastatic colon cancer. It also has been used to treat certain types of lung cancer.
According the Zalcman’s review, treatment with bevacizumab added to the chemotherapy regimen was reasonably well tolerated but did include more serious side effects.
There was a higher risk for bleeding, pulmonary hemorrhage, hypertension and arterial embolism.
In the phase III study, more patients treated with bevacizumab stopped treatment because toxicity than those receiving only chemotherapy.
However, fewer patients taking bevacizumab stopped treatment because of disease progression, compared to the chemotherapy group.
The move to add bevacizumab to the standard-of-care regimen intensified after Zalcman’s first study presentation at the American Society of Clinical Oncology (ASCO) annual meeting in 2015. The phase III study showed a median overall survival increase from 16.1 months to 18.8 months.
The NCCN changed its recommendation to add bevacizumab in 2016.
“I’ve seen the results. I absolutely believe in this approach,” Zalcman said. “I’m seeing the overall survival benefits. It works.”