The National Comprehensive Cancer Network (NCCN) has changed its first-line treatment recommendation for unresectable pleural mesothelioma, believing it will extend patient survival significantly.
The NCCN advisory panel recently added the monoclonal antibody bevacizumab to the long-standing chemotherapy combination of pemetrexed and cisplatin.
Bevacizumab, also known by brand name Avastin, inhibits the formation of new blood vessels in tumors, effectively slowing the growth of cancer cells. It has successfully treated some types of lung and colorectal cancers.
The NCCN recommendation is expected to be a precursor to the U.S. Food and Drug Administration (FDA) changing its only approved standard-of-care regimen (pemetrexed and cisplatin) for mesothelioma, which has stood since 2004.
The recommendation will soon be incorporated into the NCCN Guidelines for Patients, according to a panel spokesperson. The Journal of the National Comprehensive Cancer Network already has published it.
Bevacizumab improved survival time by 2.7 months in a recent randomized phase III clinical trial in France. The trial included 448 mesothelioma patients at 73 different sites from 2008 to 2014. All patients received a combination of pemetrexed and cisplatin, but nearly half also received bevacizumab.
The median overall survival time was 18.8 months for those also receiving bevacizumab, but 16.1 months for those receiving only the other two drugs. Those treated with bevacizumab had a median progression-free survival advantage of 9.6 months compared to 7.5 months for those not getting it.
Patients taking bevacizumab experienced more adverse side effects, but these were deemed mostly manageable, which helped lead to the NCCN recommendation.
Forty-five patients receiving bevacizumab lived at least 30 months, while only 36 of those not taking the third drug lived that long. Trial investigators believe the bevacizumab lowered the risk of death by 23 percent.
The NCCN comprises 27 prominent cancers centers around the country, including:
The group’s panel recommendation stems from considerable success with bevacizumab in clinical trials. It was discussed extensively at the American Society of Clinical Oncology (ASCO) annual meeting earlier this year in Chicago.
“The 2.7 month OS [overall survival] improvement could be viewed as slight, but it still accounts for the longest OS improvement ever obtained in a large controlled trial of pleural mesothelioma, a disease in which no progress has been accomplished since the approval of pemetrexed [more than] 10 years ago,” the panel wrote.
Also, a recent and encouraging report from China documented the addition of bevacizumab to the standard cisplatin/pemetrexed. Although it included just one mesothelioma patient and follow-up chemotherapy, it demonstrated a 14-month progression-free survival.
Pleural mesothelioma is a rare and aggressive cancer caused by exposure to asbestos fibers that can become lodged in the thin lining around the lungs. The microscopic fibers cause inflammation and scarring that may eventually lead to mesothelioma, an incurable condition with a prognosis of 9-12 months.
The NCCN guidelines still recommend surgery for patients with early-stage mesothelioma if they are healthy enough and have the epithelioid subtype of disease. The majority of patients, though, are not surgical candidates, which would include them in the new recommendations.
The downside of the new recommendations is the cost — estimated at $8,000-$10,000 monthly for bevacizumab.
Many insurance companies restrict its current use with other cancers because of cost-benefit calculations.
The FDA first approved bevacizumab in 2004 for metastatic colon cancer. The NCCA guidelines are designed to assist oncologists making treatment decisions but they are under no obligation to follow them.