Standard of care treatment for malignant pleural mesothelioma may be changing soon, based on discussions last week at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago.
Bevacizumab, a drug that restricts the growth of new blood vessels within tumors, should be added to the standard pemetrexed and cisplatin chemotherapy regimen, according to multiple doctors who attended the conference.
The drug, also known by its brand name Avastin and manufactured by Genentech, Inc., already is used regularly for colorectal cancers and some types of lung cancer. Its first FDA approval was in 2004 for metastatic colon cancer.
"It provides a significantly longer survival in patients with MPM, with acceptable toxicity, making this triplet a new treatment paradigm," wrote Dr. Gerald Zalcman, of the French Cooperative Thoracic Intergroup, in the abstract he presented at the 2015 ASCO meeting.
His lecture, and the move to change the standard of care, stems from the latest phase III randomized clinical trial that used 448 patients with unresectable pleural mesothelioma from 2008-2014. Half the patients received the bevacizumab, and everyone received the pemetrexed and cisplatin combination.
Living Longer with Bevacizumab
The median overall survival for those getting the bevacizumab was 18.6 months, compared to 16.1 months for those without it. The median progression-free survival was 9.6 months for the bevacizumab group, but only 7.5 months for the group without it.
Although the side effects were significantly higher for the group getting the bevacizumab, they were determined mostly to be manageable. The toxicities were similar to those seen in patients using the drug for other cancers, including hypertension, creatinine elevations and hemorrhage.
Of those getting the bevacizumab, 45 patients lived longer than 30 months. Only 36 with just the standard chemotherapy survived as long.
Need for a New Standard of Care for Mesothelioma
The push to change the standard of care for mesothelioma is not surprising.
It has been in place since 2003, when pemetrexed was added to cisplatin. And the survival times have remained stubbornly low, especially compared with other cancers that have seen more progress.
Dr. Natasha Leighi, from Prince Margaret Cancer Centre in Toronto, called the study's results "practice changing" during a discussion at ASCO.
"Demand for a new standard of care will exist irrespective of the cost," said Dr. Anna Nowak, of Sir Charles Gairdner Hospital in Perth, Australia. "It may be a new standard of care for some, and not for others."
Leighi said it could "cause financial toxicity."
The current use of bevacizumab with other cancers is restricted by cost-benefit calculations used by some health insurance plans and by countries with national health care systems. Estimated monthly costs are $8,000-$10,000.
During the recent trial, bevacizumab was given intravenously with chemotherapy once every three weeks for six cycles. Men with a median age of 65 comprised three-quarters of all patients in that trial, and 80 percent of all patients had the epithelioid variety of mesothelioma.
Unlike the chemotherapy drugs that attack rapidly dividing cancer cells, bevacizumab restricts the flow of necessary nutrients and oxygen the cells need to divide and grow.
Leighi predicted during discussion that the trial, along with previous evidence, will soon change the standard of care.
More Discussions About Mesothelioma at ASCO Meeting
There were other abstracts involving mesothelioma presented at the ASCO, adding even more optimism about potential treatment advances.
Dr. Raffit Hassan, mesothelioma specialist from the National Cancer Institute, detailed results of a phase I trial involving immunotherapy drug CRS-207 in combination with standard chemotherapy.
Disease control was obtained in 30 of the 32 trial participants. There was partial response in 19 patients and stable disease in 11. CRS-207 is given by vaccination. Median duration of response was 5 months and median progression-free survival was 7.4 months.
Dr. Diego Cortinovis, San Gerardo Hospital in Monza, Italy, reported impressive results for the anti-tumor drug trabectedin in a phase II study involving second-line treatment for sarcomatoid/biphasic mesothelioma. Trabectedin has been used effectively in soft-tissue sarcomas and for relapsed ovarian cancers.