Results from a phase 3 clinical trial were recently published in the Journal of Clinical Oncology showing that a combination of chemotherapy and immunotherapy for mesothelioma improves patients’ survival more than chemotherapy alone. Researchers combined Keytruda, or pembrolizumab, with platinum and pemetrexed chemotherapy. The overall response rate for patients receiving chemotherapy and Keytruda was 63 percent versus 40 percent for those just receiving chemotherapy. The patients who received chemoimmunotherapy did better than those just receiving chemotherapy. Keytruda works by targeting the PD-1 receptor on lymphocytes, which allows the immune system to target tumors better. Patients with either PD-L1-positive or PD-L1-negative tumors experienced better survival outcomes.
Preliminary results were announced in June by the pharmaceutical company Merck. Research found that the combination of Keytruda and chemotherapy reduced the risk of death in mesothelioma patients by 21 percent. There were 440 patients in the study with pleural mesothelioma who never received prior treatment. Patients who received chemoimmunotherapy had a median overall survival of 17.3 months compared to 16.1 months for patients receiving chemotherapy alone. Patients who had non epithelioid mesothelioma cell types had better outcomes than those with epithelioid cell types. There were around 20 percent of participants with grade 3 or higher adverse events. The most common was fatigue. Researchers also found that the tolerability was acceptable.
There is another study called DREAM3R that is looking at survival outcomes for patients who receive different types of chemoimmunotherapy regimens versus chemotherapy and immunotherapy by themselves. The chemoimmunotherapy part of the study is looking at Keytruda alongside durvalumab, which is an anti-PD-L1 antibody. Researchers hope the study will not take long so we can know which treatment, either chemoimmunotherapy or Ipilimumab and nivolumab, is better. Ipilimumab and nivolumab are approved as a first line treatment for unresectable pleural mesothelioma.
Epithelioid patients do not benefit from immunotherapy, but a certain subgroup of epithelioid patients could possibly benefit from certain treatment combinations. Researchers are having trouble with receiving approval for certain treatment combinations though. Based on data from this and other studies, researchers believe these treatments should be made available to more patients. Chemoimmunotherapy is clearly better than chemotherapy alone and even though it is not yet approved by the FDA, it is still an option for patients. This is why clinical trials are so important. With treatments continuously evolving, there will be more options and better survival outcomes for patients with serious cancers like mesothelioma.
Sources:
“KEYTRUDA® (pembrolizumab) Plus Chemotherapy Significantly Improved Overall Survival Versus Chemotherapy Alone as First-Line Treatment for Unresectable Advanced Pleural Mesothelioma” Business Wire (June 3, 2023). [Link]
Meg Barbor, “Phase III Trial Reports Chemoimmunotherapy Is Superior to Chemotherapy Alone in Malignant Pleural Mesothelioma” Asco Post (September 10, 2023). [Link]
“Pembrolizumab in Patients With Advanced Malignant Pleural Mesothelioma” clinicaltrials.gov [Link]
Quicy S. Chu et al., “IND227 phase III (P3) study of cisplatin/pemetrexed (CP) with or without pembrolizumab (pembro) in patients (pts) with malignant pleural mesothelioma (PM): A CCTG, NCIN, and IFCT trial” Journal of Clinical Oncology [Link]
