Individual patient data was obtained from 87 trials (16,485 patients).
Chemotherapy increased overall survival (HR 0.88, 95% CI 0.85 to 0.92) with an absolute benefit of 4.5% at five years. Event-free survival was increased by chemotherapy (HR 0.87, 95% CI 0.84 to 0.90). There was significant heterogeneity (I2=41%) for overall survival, which was explained in part by timing. There was a statistically significant benefit of concomitant chemotherapy on overall survival (HR 0.81, 95% CI 0.78 to 0.86), but not for induction chemotherapy (HR 0.96, 95% CI 0.90 to 1.02).
A subset of six trials allowed direct comparison of timing. There was no benefit of concomitant chemotherapy for overall survival (HR 0.88, 95% CI 0.77 to 1.04), but improved outcomes for event-free survival (HR 0.81, 95% 0.69 to 0.96) and loco-regional failure (HR 0.77, 95% CI 0.64 to 0.92).
Within concomitant chemotherapy there was a decreasing effect of chemotherapy with age (p=0.003). Other individual patient characteristics were not significant.