Randomized Phase III Trial Comparing Switch-Maintenance Pemetrexed with Observation Followed by Pemetrexed at Progression in Advanced NSCLC.

Abstract Objectives: Two phase III trials show that maintenance pemetrexed therapy after platinum-doublet chemotherapy prolongs overall survival (OS) and progression free survival (PFS) in advanced non-squamous non-small-cell lung cancer (NSCLC). However, few patients in the control arms received pemetrexed at progression in these trials, performance status (PS) two patients were ineligible and few of the participants were elderly. Thus, we designed this study comparing immediate switch-maintenance pemetrexed therapy with pemetrexed at progression after platinum-doublet chemotherapy. Methods: Patients with stage IIIB/IV non-squamous NSCLC, ≥18 years, PS 0–2, and non-progression after four courses of carboplatin/vinorelbine were randomized to receive immediate maintenance pemetrexed therapy or observation followed by pemetrexed at progression. The primary endpoint was OS, secondary endpoints were PFS, toxicity and health related quality of life (HRQoL). Results: 105 patients were randomized between May 2014 and September 2017. Median age was 67 years, 36% were >70 years, 9% had PS 2, 91% stage IV and 47% were women. In the observation arm, 73% received pemetrexed at progression. Patients in the maintenance arm had a numerically longer OS (median 12.0 vs. 10.0 months; p = .10) and a statistically significant longer PFS (median 3.1 vs. 1.9 months; p < .01). In multivariable analyses adjusting for baseline characteristics, there was a trend toward improved OS (HR 0.65, 95% CI 0.42–1.01); p = .05), and a significantly improved PFS (HR 0.53, 95% CI 0.35–0.80; p < .01). There were no significant differences in toxicity or HRQoL between the treatment arms. Conclusion: There was a trend toward prolonged OS and significantly longer PFS from switch- maintenance pemetrexed therapy when 73% of patients in the control arm received pemetrexed at progression. ClinicalTrials.gov Identifier: NCT02004184