Randomized Study of Maintenance Pemetrexed Versus Observation for Treatment of Malignant Pleural Mesothelioma: CALGB 30901

• Published in: Clinical lung cancer 2020-11, Vol.21 (6), p.553-561.e1
• Main Authors: Dudek, Arkadiusz Z., Wang, Xiaofei, Gu, Lin, Duong, Stephanie, Stinchcombe, Thomas E., Kratzke, Robert, Borghaei, Hossein, Vokes, Everett E., Kindler, Hedy L.
• Format: Article
• Language: English
• Subjects: Continuation pemetrexed; Phase II study; Progression-free survival; Unresectable mesothelioma
• ISSN: 1525-7304; 1938-0690
• DOI: 10.1016/j.cllc.2020.06.025

The role of maintenance therapy for malignant pleural mesothelioma (MPM) is unknown. We performed a randomized phase II trial to determine if continuation of pemetrexed after first-line pemetrexed and platinum would improve progression-free survival (PFS). Eligible patients with unresectable MPM, without disease progression following 4 to 6 cycles of pemetrexed and platinum were randomized 1:1 to observation or continuation of pemetrexed until progression, stratified by number of cycles (< 6 or 6), cis- or carboplatin containing regimen, and histology. Study size was calculated based on the assumption that observation would produce a median PFS of 3 months and pemetrexed would yield median PFS of 6 months. A total of 72 patients were registered from December 2010 to June 2016. The study closed early after 53 patients were randomized; 49 eligible (22 on the observation arm and 27 on the pemetrexed arm) were included in the analysis. The median PFS was 3 months (95% confidence interval [CI], 2.6-11.9 months) on observation and 3.4 months (95% CI, 2.8-9.8 months) on pemetrexed (hazard ratio [HR], 0.99; 95% CI, 0.51-1.90; P = .9733). The median overall survival (OS) was 11.8 months (95% CI, 9.3-28.7 months) for observation, and 16.3 months (95% CI, 10.5-26.0 months) for pemetrexed (HR, 0.86; 95% CI, 0.44-1.71; P = .6737). Grade 3 or 4 toxicities on the pemetrexed arm included anemia (8%), lymphopenia (8%), neutropenia (4%), and fatigue (4%). A higher baseline level of soluble mesothelin-related peptide was associated with worse PFS (HR, 1.86; 95% CI, 1.00-3.46; P = .049). Maintenance pemetrexed following initial pemetrexed and platinum chemotherapy does not improve PFS in patients with MPM. The role of maintenance therapy after first-line platinum and pemetrexed for malignant pleural mesothelioma is unknown. We performed the first-to-date randomized trial to determine if continuation of pemetrexed would improve progression-free survival over that of observation and found that primary endpoint was not different between study arms. Therefore, we cannot recommend pemetrexed continuation maintenance for treatment of malignant pleural mesothelioma.