Seven RCTs were included in the review (3,973 participants, range 239 to 745). All trials described the allocation system and performed a power calculation. However all trials had unclear handling of missing data and did not provide details of assessor blinding. Five trials reported the blinding of caregivers; six trials had patient blinding. Only one trial reported the presence of allocation concealment.
Primary outcome: There was a non-significant increase in overall survival for gemcitabine chemotherapy plus molecular-targeted therapies (HR 0.941, 95% CI 0.877 to 1.010; seven RCTs) compared with gemcitabine alone. A sensitivity analysis was performed excluding the only trial with a significant effect (median survival 6.24 months with molecular targeted therapies and 5.91 months without, so it was considered an outlier); the result was not significant.
Secondary outcomes: There was a significant improvement in progression-free survival (HR 0.862, 95% CI 0.797 to 0.933; five RCTs) and overall response rate (OR 1.356, 95% CI 1.054 to 1.744; seven RCTs) for gemcitabine plus molecular-targeted therapies compared with versus gemcitabine alone. However, gemcitabine plus molecular-targeted therapies versus gemcitabine alone showed significantly more common grade 3 and 4 toxicities (OR 1.793, 95% CI 1.508 to 2.132; seven RCTs) and a significantly higher risk of treatment-related mortality (grade 5 toxicities; (OR 2.192, 95% CI 1.198 to 4.009; six RCTs).
Sensitivity analyses for study quality did not change the results.
The funnel plot showed no evidence of publication bias.