Meta-analysis examining impact of age on overall survival with pemetrexed for the treatment of advanced non-squamous non-small cell lung cancer.

OBJECTIVE: In clinical practice, elderly patients are often undertreated relative to younger patients. This meta-analysis was designed to determine whether older patients with non-squamous non-small cell lung cancer (NSCLC) could derive an overall survival (OS) benefit from pemetrexed treatment comparable to that experienced by younger patients in the first-line, second-line, or maintenance settings.

METHODS: Data from 2671 patients with non-squamous NSCLC participating in four pemetrexed phase III studies were included in a meta-analysis using a random-effects model. Studies included were: JMEI (second-line pemetrexed, N=399); JMDB (first-line pemetrexed/cisplatin, N=1252); JMEN (pemetrexed maintenance after non-pemetrexed/platinum doublet, N=481); and PARAMOUNT (pemetrexed maintenance after first-line pemetrexed/cisplatin, N=539). Patients were predominantly Eastern Cooperative Oncology Group performance status (PS) 0/1. The ratio of OS hazard ratio (HR) (pemetrexed versus control) for younger patients over that for older patients within each study was used as the measure of the differential effect of pemetrexed. Data were examined using age cutoffs of 65 and 70 years.

RESULTS: Among the four studies, 32% of patients were aged ≥65 years and 14% were aged ≥70 years. The test of heterogeneity among studies was non-significant for subgroups defined by age 65 (P=0.083) and age 70 (P=0.848). The pooled ratio of the OS HR (pemetrexed versus control) in patients <65years to that in patients ≥65 years was 0.92 (95% confidence intervals [CI] 0.67-1.25). Similar results were seen for the analysis using the age 70 years cut-off (0.80 [95% CI 0.62-1.04]).

CONCLUSIONS: In patients with non-squamous NSCLC with good PS, the effect of pemetrexed on OS was not found to be different in younger and older patients undergoing treatment in the first-line, second-line, or maintenance settings.