Results from a phase 2 trial combining immunotherapy with standard of care shows promising response in patients suffering with malignant mesothelioma.
Majority of mesotheliomas are caused due to exposure to asbestos resulting in aggressive cancer with a characteristic inflammation in the pleural cavity. These cancers have a low mutational burden with alterations in few key tumor suppressive genes such as BAP1, NF2 and CDKN2AB. The current standard of care includes a combination of cisplatin and pemetrexed, however, despite available treatment options, the overall survival remains very low. Similar to non-small cell cancers where immunotherapy has been combined with chemotherapy, such combinations are now being explored in mesotheliomas too.
A multicenter phase II-study (PrE0505) enrolled 55 patients with untreated, unresectable mesotheliomas. Patients received 1,120 mg of durvalumab once every three weeks in combination with standard chemotherapy (standard dose of cisplatin plus pemetrexed for up to six cycles). Majority (82%) of patients were males with a median age of 68 years (range: 35-83), and 75% of tumors were epithelioid. The primary endpoint of the study was overall survival (OS).
For patients enrolled between 12 June 2017 and 21 June 2018 and treated with this combination of immunotherapy with chemotherapy, the median follow up was 24.2 months with 33 deaths at the time of analysis. A significantly longer OS of 20.4 months was seen in participants as compared to 12 months of historical controls (95% confidence interval (CI): 13.0–28.5; 80%-CI: 15.1–27.9; P=0.0014; hazard ratio [HR]=0.034). In addition, median progression free survival (PFS) was 6.7 months (95%-CI: 6.1–8.4; 80%-CI: 6.3–8.2).
The group of patients with epithelioid type mesotheliomas had a significantly longer median OS (24.3 months versus 9.2 months; HR=0.27, 95%-CI: 0.13–0.57; P<0.001) and PFS (8.2 months versus 4.9 months; HR=0.30; 95%-CI: 0.16–0.58; P<0.001) as compared to non-epithelioid patients. Safety results were consistent with the known tolerability profile of the drugs, and no new safety concerns were reported during the study.
The proposed combination in phase II-study shows encouraging results for unresectable mesothelioma patients. It is important to extend these studies to a larger group of patients for studying the efficacy of proposed treatment strategy.
Forde PM, Anagnostou V, Sun Z, et al. Durvalumab with platinum-pemetrexed for unresectable pleural mesothelioma: survival, genomic and immunologic analyses from the phase 2 PrE0505 trial. Nat Med. 2021 Nov;27:1910-20.