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

Abstract

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. Background: 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). Patients and Methods: 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. Results: 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 ¼ .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 ¼ .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 ¼ .049). Conclusion: Maintenance pemetrexed following initial pemetrexed and platinum chemotherapy does not improve PFS in patients with MPM.

Malignant pleural mesothelioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up☆

“…No improvement in PFS or OS was observed. [46] A randomised phase II trial (NVALT19; NTR4132) tested a switch to maintenance gemcitabine versus best supportive care (BSC) after four to six cycles of platinum-pemetrexed. PFS was significantly longer with gemcitabine, but there was no OS benefit.…”

Hyaluronic Acid Correlates With Bone Metastasis and Predicts Poor Prognosis in Small-Cell Lung Cancer Patients

“…E-EL-H1347c, Elabscience Biotechnology Inc., China). The evaluation was performed according to the protocol of the manufacturer and based on previous studies (25,26).…”

A Glimpse in the Future of Malignant Mesothelioma Treatment

“…Carboplatin can be used in patients unfit for Cisplatin ( Ceresoli et al, 2006 ). There is currently no evidence supporting maintenance therapy for patients achieving disease control, with many studies demonstrating no benefit from the prosecution of Pemetrexed, the latest being the CALGB 30901 trial ( Dudek et al, 2020 ). The addition of antiangiogenics to chemotherapy has been considered since MMe is well known for its high VEGFR expression ( Aoe et al, 2006 ).…”