Fifteen RCTs (n=4,465 patients, range 83 to 832) were included in the review.
Compared with gemcitabine alone, significant survival benefits were observed for any gemcitabine-based combination therapy (HR 0.91, 95% CI 0.85 to 0.97; I2=0%; 15 RCTs), fluoropyrimidine-based combinations (HR 0.90, 95% CI 0.81 to 0.99; I2=0%; six RCTs), and platinum-based combinations (HR 0.85, 95% CI 0.76 to 0.96; I2=0%; five RCTs ). No risk reduction was observed in the group of trials combining gemcitabine with irinotecan, exatecan or pemetrexed (four RCTs).
For patients with a good performance status, a significant benefit from combination chemotherapy was observed (HR 0.76, 95% CI 0.67 to 0.87; I2=0%, five RCTs), but patients with an initially poor performance status did not appear to benefit from combination chemotherapy (five RCTs).
Funnel plots suggested a low likelihood of publication bias.