Bratislava Medical Journal Vol.115, No.4, p.233-237, 2014

Purpose: This meta-analysis investigated pemetrexed-based doublet compared with pemetrexed alone as second-line therapy for patients with advanced non-small cell lung cancer.
Methods: Randomized controlled trials which compared pemetrexed-based doublet with single-agent pemetrexed in patients as second-line treatment of advanced non-small cell lung cancer were searched. Overall survival (OS) was the primary end point, while secondary end points included progression-free survival, overall response rate, 1-year survival rate, and grade 3 or 4 toxicity.
Results: Four eligible randomized clinical trials including 1,084 patients were selected.

Meta-analysis demonstrated that pemetrexed-based doublet arm significantly improved the overall response rate (OR=2.70, 95% CI: 1.76–4.15, p=0.000), compared with docetaxel alone group, while there were no significant differences in overall survival (HR=0.88, 95% CI: 0.74–1.04, p=0.132), progression-free survival (HR=0.91, 95% CI: 0.73–1.15, p=0.443), and 1-year survival rate (OR=1.43, 95% CI: 0.85–2.40, p=0.178) between the two arms.

However, there were more frequencies of grade 3–4 leucopenia (OR=2.86, 95% CI: 1.32–6.20, p=0.008), neutropenia (OR=2.69, 95% CI: 1.55–4.68, p=0.000) and thrombocytopenia (OR=6.92, 95% CI: 2.51–19.07, p=0.000) in pemetrexed-based doublet group.

Grade 3–4 anemia (OR=0.62, 95% CI: 0.33–1.18, p=0.144) and fatigue (OR=1.15, 95% CI: 0.73–1.79, p=0.550) had equivalent incidences in the two groups.

Conclusions: This is the first meta-analysis to compare pemetrexed-based doublet with single-agent pemetrexed in second-line therapy of non-small cell lung cancer. Our meta-analysis suggested that pemetrexed combination chemotherapy was not superior to single-agent arm and was not recommended as the second-line chemotherapy for patients with non-small cell lung cancer (Tab. 2, Fig. 6, Ref. 20).