The differential efficacy of pemetrexed according to NSCLC histology: A review of two phase III studies

Background. Recent studies of pemetrexed have identified a predictive role for non-small cell lung cancer (NSCLC) histology. We further reviewed the differential efficacy of pemetrexed according to histology in two large, phase III NSCLC trials. Methods. One study tested pemetrexed versus do-cetaxel in previously treated patients (n = 571) and the other tested cisplatin plus pemetrexed versus cisplatin plus gemcitabine in chemotherapy-naive patients (n = 1,725) with advanced NSCLC. Cox proportional hazard models were used to test for covariate-adjusted treatment-by-histology interactions (THIs) for overall survival (os) and progression-free survival (PFs). For each histologic subgroup, the Kaplan-Meier method was used to estimate unadjusted within-arm medians, and Cox models were used to estimate covariate-ad- justed between-arm hazard ratios (HRs). Results. In both studies, treatment arms were well balanced for histology. THis were statistically significant (p < .005) for both OS and PFS. Nonsquamous patients treated with pemetrexed-based therapy experienced longer survival than the comparators (HR, 0.78 and 0.84, respectively), whereas squamous patients had shorter survival (HR, 1.56 and 1.23, respectively). Whereas the efficacy of pemetrexed regimens differed according to histology, it did not differ for docetaxel or for cisplatin plus gemcitabine. Pemetrexed was well tolerated across histologic groups.