The U.S. Food and Drug Administration (FDA) expanded its approval of pembrolizumab for first-line treatment of metastatic non-small cell lung cancer last week, moving it closer to becoming a viable treatment option for patients with pleural mesothelioma.
Pembrolizumab is marketed by Merck & Co. under the brand name Keytruda.
It helps the body’s immune system detect and destroy cancer cells.
The FDA approved its first-line use in combination with pemetrexed and carboplatin, two chemotherapy agents used regularly for mesothelioma.
Pembrolizumab, the most well-known immunotherapy drug, is being studied for use with various cancers in more than 400 clinical trials worldwide, including 10 for mesothelioma but none in combination with chemotherapy.
The FDA previously approved its use for melanoma, head and neck cancers and Hodgkin lymphoma.
Before last week’s expansion, pembrolizumab was approved for non-small cell lung cancer (NSCLC), but only as a single agent and only with tumors that expressed the PD-L1 protein.
That protein is found in many cancers, but only in half of mesothelioma patients. This was the first approval as part of a chemotherapy combination and the first without a need for PD-L1 expression.
“Now that there is clinical evidence the combination is effective in a common malignancy like lung cancer, the next logical step is to test it in other cancer types, including rare ones like mesothelioma,” Dr. Raymond Wong, research scientist at the Pacific Mesothelioma Center in Los Angeles, told Asbestos.com. “The outcome of those trials could very well result in a new first-line treatment for mesothelioma.”
The recent FDA approval is based on data from the latest clinical trial that demonstrated almost double the effectiveness in patients diagnosed with NSCLC who were given the study drug.
Fifty-five percent of the patients responded well to the combination of pembrolizumab and chemotherapy, compared to just 29 percent who received chemotherapy alone. None had previously received any systemic therapy.
Of the responders getting pembrolizumab, 93 percent went for at least six months, compared to 81 percent for those receiving only chemotherapy.
The median progression-free survival was 13 months for those getting the combination and just 8.9 months for patients receiving chemotherapy alone.
“This approval marks an important milestone in the treatment of lung cancer…irrespective of PD-L1 expression,” Dr. Corey Langer, lead investigator in the clinical trial, said in a press release. “Physicians should continue to use each patient’s individual characteristics — including biomarker status, histology, and other clinical factors — to determine the best treatment plan for each person.”
The addition of pembrolizumab did increase chances of serious side effects from 28 percent (who did not receive it) to 41 percent (who received it). The most common side effects were nausea, fatigue and constipation.
Acute kidney problems were the most common problem among the 10 percent who discontinued use of pembrolizumab.
Pembrolizumab already has shown effectiveness with some mesothelioma patients who are receiving the drug under the Merck Access Program.
Mesothelioma survivor Walter Merth, who is being treated at the Abramson Cancer Center in Philadelphia, started taking the drug early in 2016 when his cancer re-emerged just two months after aggressive surgery.
He credited the drug for his significant turnaround.
In an ongoing multicenter clinical trial involving pembrolizumab and second-line therapy, more than half of the 25 mesothelioma patients in the study experienced initial tumor reduction with an average time before disease progression of six months.
“It seems to work well in certain cases,” said Dr. Tawee Tanvetyanon, oncologist at the Moffitt Cancer Center in Tampa. “We still don’t have enough data to say for sure, but yes, it [pembrolizumab] could become the next big thing for mesothelioma.”