This 5-year follow-up analysis from the CheckMate 743 randomized controlled trial evaluated updated efficacy, safety, and biomarker outcomes for first-line nivolumab plus ipilimumab versus chemotherapy in patients with unresectable pleural mesothelioma. With a median follow-up of 66.8 months, nivolumab plus ipilimumab demonstrated a continued overall survival benefit compared to chemotherapy in all randomly assigned patients, with 5-year OS rates of 14% versus 6% (hazard ratio [HR] 0.74, 95% CI 0.62 to 0.88). This benefit was observed regardless of tumor histology. Among biomarker-evaluable patients treated with nivolumab plus ipilimumab (n=242), exploratory analyses showed that high baseline monocytic myeloid-derived suppressor cell (M-MDSC) levels correlated with worse OS compared to low M-MDSC levels (HR 1.25, 95% CI 1.09 to 1.43). A treatment-switching analysis was performed, adjusting for the 24% of patients in the chemotherapy arm who received subsequent immunotherapy; after this adjustment, nivolumab plus ipilimumab continued to demonstrate an OS benefit versus chemotherapy (HR 0.64, 95% CI 0.53 to 0.78). The study reported no new safety signals. The authors conclude that these results demonstrate long-term, durable clinical benefit with nivolumab plus ipilimumab versus chemotherapy, which was preserved even after adjustment for treatment switching in the chemotherapy arm. Exploratory analyses suggested greater benefit with nivolumab plus ipilimumab in the low M-MDSC subgroup. The results further support first-line nivolumab plus ipilimumab as a standard of care for unresectable pleural mesothelioma.
For people diagnosed with advanced pleural mesothelioma, a cancer of the lining of the lungs that can't be removed by surgery, the question has been whether a newer type of treatment called immunotherapy offers lasting help. This five-year follow-up from a major clinical trial provides an answer. The treatment, a combination of the immunotherapy drugs nivolumab and ipilimumab, continues to show a survival benefit compared to standard chemotherapy. After a median follow-up of over five and a half years, 14% of patients on the immunotherapy combination were alive at five years, compared to 6% of those who started on chemotherapy. This benefit was seen regardless of the specific type of mesothelioma tumor. The study also looked at a potential biomarker—a sign in the blood that might predict who benefits most. They found that patients with lower levels of a certain immune cell type (called M-MDSCs) before treatment tended to do better on the immunotherapy combination. Importantly, the survival advantage for the immunotherapy-first group remained even after the researchers accounted for the fact that nearly a quarter of patients in the chemotherapy group later received immunotherapy. No new safety concerns emerged with longer follow-up. These results confirm that the immunotherapy combination provides a durable, long-term benefit for some patients with this challenging cancer.
What this means for you: A two-drug immunotherapy combo provides lasting survival benefit over chemo for advanced mesothelioma, even after five years.
View Original Abstract ↓
In this 5-year follow-up from the CheckMate 743 study in patients with unresectable pleural mesothelioma (PM), we evaluated updated efficacy and safety outcomes and biomarkers and performed treatment-switching analyses with first-line nivolumab plus ipilimumab versus chemotherapy. With a median follow-up of 66.8 months, nivolumab plus ipilimumab demonstrated continued overall survival (OS) benefit versus chemotherapy in all randomly assigned patients (5-year OS rates, 14% 6%; hazard ratio [HR], 0.74 [95% CI, 0.62 to 0.88]); similar benefit was observed regardless of tumor histology. Of biomarker-evaluable patients treated with nivolumab plus ipilimumab (n = 242), high baseline monocytic myeloid-derived suppressor cell (M-MDSC) levels correlated with worse OS versus low M-MDSC levels (HR, 1.25 [95% CI, 1.09 to 1.43]). After adjusting for 24% of patients in the chemotherapy arm who received subsequent immunotherapy, nivolumab plus ipilimumab demonstrated continued OS benefit versus chemotherapy (HR, 0.64 [95% CI, 0.53 to 0.78]). No new safety signals were observed. These results demonstrate long-term, durable clinical benefit with nivolumab plus ipilimumab versus chemotherapy, which continued to be preserved even after treatment-switching adjustment in the chemotherapy arm. Exploratory analyses suggested greater benefit with nivolumab plus ipilimumab in the low M-MDSC subgroup. These results further support first-line nivolumab plus ipilimumab as standard of care for unresectable PM.