Ten phase III RCTs were included in the review (n=3,811 patients): three RCTs of prostate cancer, three RCTs of multiple myeloma, two RCTs of chronic lymphocytic leukaemia, one RCT of lung cancer, and one RCT of follicular lymphoma. Four trials reported the method of randomisation. Allocation concealment was adequate in five trials. None of the trials reported blinding of outcome assessors. Eight trials used intention-to-treat analyses. Six trials provided the description of withdrawals. Three trials reported the sample size calculation.
Overall survival: Early first-line treatment was associated with a significant benefit in overall survival in patients with prostate cancer compared with late first line treatment (HR1.23, 95% CI 1.11 to1.37; three RCTs). There was no significant difference in overall survival between the two early and late treatment in multiple myeloma, chronic lymphocytic leukaemia, follicular lymphoma or lung cancer.
Progression-free survival: Compared with late first-line treatment, early first-line treatment was associated with a significant benefit in progression-free survival in patients with prostate cancer (HR 1.67, 95 CI 1.37 to 2.05; two RCTs, three comparisons), chronic lymphocytic leukaemia (HR 1.95, 95% CI 1.19 to 3.21; two RCTs) and multiple myeloma (HR 4.39, 95% 1.82 to 10.56; two RCTs). There was no significant benefit in progression-free survival with early first-line treatment in follicular lymphoma.
Response rate: There was no significant difference in response rate between early and late treatment for patients with multiple myeloma, chronic lymphocytic leukaemia or lung cancer.
No significant heterogeneity was observed in any of these outcomes. Sensitivity analyses did not materially alter the results.
There was no evidence of publication bias.