There has been a setback for researchers focused on the promise of pembrolizumab for mesothelioma.
New research suggests that pembrolizumab (Keytruda) may not be the miracle mesothelioma drug that some were hoping for.
The Phase III trial results were presented at a the European Society of Medical Oncology conference now underway in Spain. They suggest that pembrolizumab for mesothelioma may be no better than chemotherapy for improving survival.
Pembrolizumab for Mesothelioma: How it Works
Malignant pleural mesothelioma is a rare but lethal cancer. It is usually associated with on-the-job asbestos exposure. There is no cure. The only drug approved for mesothelioma treatment is Alimta (pemetrexed).
Cancer researchers around the world are working hard to find other mesothelioma treatments. Pembrolizumab for mesothelioma is one of the most talked-about possibilities.
Pembrolizumab is a monoclonal antibody. It blocks a protein called PD-1 from binding to the surface of cancer cells. Scientists believe that PD-1 suppresses the immune system in up to 40 percent of people with mesothelioma.
By blocking PD-1, pembrolizumab may help turn that mechanism back on. This is why it is classified as an immunotherapy drug.
Early Promise for Keytruda
The FDA approved pembrolizumab for relapsed lung cancer in 2015. Their decision was based on the results of some promising clinical trials.
In one trial, 76 percent of mesothelioma patients responded to Keytruda. Mesothelioma tumors temporarily stopped growing in about half of the patients. About a quarter of the patients in the trial experienced some amount of tumor shrinkage.
Another trial (KEYNOTE-028) of pembrolizumab for mesothelioma showed a 20 percent response rate and progression free survival of 5.4 months. That trial focused on patients with relapsed cancer.
Disappointing Results with Pembrolizumab for Mesothelioma
In the new Phase III study, doctors divided 144 relapsed mesothelioma patients into two groups. One group received 200 mg of Keytruda every three weeks. The second group had standard chemotherapy.
Lead study author Sanjay Popat, PhD, with the UK’s Royal Marsden NHS Foundation Trust presented the data.
Dr. Popat told his colleagues that it took a median of 2.5 months for tumors to start growing again with pembrolizumab for mesothelioma. Patients on chemotherapy had a median progression-free survival of 3.4 months.
“The trial did not meet the primary endpoint of improving PFS with pembrolizumab over single-agent chemotherapy in PD-L1 unselected patients,” said Dr. Popat.
At a median follow-up of 11.8 months, the median overall survival was 10.7 months for pembrolizumab and 11.7 months for chemotherapy. Patients on pembrolizumab had a slightly lower rate of complications.
The researchers conclude that more research is needed to determine which subgroups are most likely to benefit from pembrolizumab for mesothelioma.
Popat S, Cunoni-Fontecedro A, Polydoropoulou V, et al. A multicenter randomized phase III trial comparing pembrolizumab (P) vs single agent chemotherapy (CT) for advanced pre-treated malignant pleural mesothelioma (MPM)—results from the European Thoracic Oncology Platform (ETOP 9-15) PROMISE-meso trial. Presented at: 2019 ESMO Congress; September 27 to October 1, 2019. Abstract LBA91.
Columbus, Gina, “Pembrolizumab Misses PFS Endpoint in Relapsed Malignant Pleural Mesothelioma”, OncLive website, September 30, 2019, https://www.onclive.com/conference-coverage/esmo-2019/pembrolizumab-misses-pfs-endpoint-in-relapsed-malignant-pleural-mesothelioma?p=2