Effectiveness and safety of pemetrexed-based doublet versus pemetrexed alone as second-line treatment for advanced non-small-cell lung cancer: a systematic review and meta-analysis

To compared pemetrexed-based doublet with single-agent pemetrexed as second-line treatment for advanced non-small-cell lung cancer We systematically searched for randomized clinical trials that compared pemetrexed-based doublet with single-agent pemetrexed in patients with histologically proven non-small-cell lung cancer. The primary end point was overall survival. Secondary end points were progression-free survival, overall response rate and grade 3 or 4 toxicity. Data were extracted from the studies by 2 independent reviewers. The meta-analysis was performed by Stata version 10.0 software (Stata Corporation, College Station, Texas, USA). Five randomized clinical trials (totally 1,186 patients) were eligible. Meta-analysis showed that there was significant improvement in PFS (HR 0.82, 95% CI 0.71-0.95, P = 0.007) and overall response rate (OR 2.39, 95% CI 1.58-3.62, P = 0.000) in pemetrexed-based doublet group, compared with pemetrexed alone, though the pooled HR for overall survival (HR 0.89, 95% CI 0.76-1.04; P = 0.129) showed no significant difference between the two groups. However, there were more incidences of grade 3 or 4 neutropenia (OR 2.3, 95% CI 1.4-3.77, P = 0.001), thrombocytopenia (OR 6.41, 95% CI 2.57-16.0, P = 0.000), and leucopenia (OR 2.45, 95% CI 1.13-5.34, P = 0.024) in pemetrexed-based doublet group. With regard to the risk of grade 3 or 4 anemia (OR 0.71, 95% CI 0.17-2.91, P = 0.629) and fatigue (OR 1.47, 95% CI 0.92-2.35, P = 0.104), there was no significant difference between the two groups. Pemetrexed-based doublet therapy didn't gain any benefit in survival but significantly improved PFS and better ORR compared with single-agent pemetrexed as second-line therapy for advanced non-small-cell lung cancer. However, more incidences of grade 3 or 4 neutropenia, thrombocytopenia, and leucopenia were observed in pemetrexed-based doublet group.