[Impact of histology on efficacy of pemetrexed: pemetrexed in second-line setting and as maintenance therapy after first-line treatment in Chinese patients with advanced NSCLC].

OBJECTIVE: To evaluate the impact of histology on efficacy of pemetrexed in Chinese non-small cell lung cancer (NSCLC) patients. This report summarized the results of two clinical trials of pemetrexed in Chinese patients with advanced NSCLC in 2nd line setting and maintenance setting after 1st line (JMID study and Chinese subgroup from JMEN study) treatment.

METHODS: For the Chinese JMID study (second-line), Chinese patients with locally advanced or metastatic (stage IIIA, IIIB or IV) NSCLC who had prior chemotherapy were enrolled. The study was designed to investigate the noninferiority of pemetrexed (500 mg/m(2), day 1 of each 21-day cycle) to docetaxel (75 mg/m(2), day 1 of each 21-day cycle) in terms of overall survival (OS). For the global JMEN study (maintenance), patients initially diagnosed with IIIB or IV NSCLC, those who had not progressed after completing at least four cycles of platinum-based chemotherapy were enrolled to test for the superiority of pemetrexed (500 mg/m(2), day 1 of each 21-day cycle) over placebo with progression free survival (PFS) as primary endpoint.

RESULTS: In JMID study, the OS was similar between the pemetrexed group (Pem group) and docetaxel group (Doc group). Retrospective histological subtype analysis showed survival benefits (both OS and PFS) numerically of non-squamous patients over squamous patients in the Pem group (OS: HR 0.74, 95% CI 0.45-1.21, P = 0.2267, median 11.7 vs. 9.7 months; PFS: HR 0.77, 95% CI 0.44-1.34, P = 0.3585, median 3.0 vs. 1.7 months). In the Chinese subgroup of JMEN study, the median PFS in the Pem group for squamous and nonsquamous patients was 4.2 and 1.5 months for squamous patients, the median OS in the Pem group for squamous and nonsquamous patients was 22.5 and 6.2 months for squamous patients. In JMEN China subgroup analysis, the HR on histology was not analyzed due to the small sample size. In terms of safety profile, drug-related grade 3 or 4 hematological toxicities (leukocytopenia and neutropenia) events occurring after second-line treatment were significantly lower in the Pem group than in the Doc group (both P < 0.001). Similarly in patients receiving pemetrexed maintenance after first-line treatment, incidences of toxicity events were low.

CONCLUSIONS: Consistent with global results, in Chinese NSCLC patients, histology has an impact on the efficacy of pemetrexed, in which non-squamous histology predicts a positive outcome for patients treated with pemetrexed. In terms of overall safety, pemetrexed is better than docetaxel with a lower incidence of adverse events and anticipates manageable safety profile in NSCLC patients. Based on consistent Chinese data from the two studies, pemetrexed is recommended as a standard chemotherapy regime in both second-line and maintenance setting after first-line treatment for Chinese non-squamous NSCLC patients.