Twenty-one trials were included in the review (n=3,687 patients; number cited in figure 1). There were 11 RCTs of chemotherapy, six RCTs of interferons, one RCT of vandetanib, one RCT of thalidomide, one RCT of marimastat, and one RCT of Bec2/BCG vaccine. The included trials were generally poorly reported and may be at risk of bias. Only five trials reported an adequate method of allocation concealment, three reported blinding, and six reported an intention-to-treat analysis.
Total population (all drugs): Compared with control, maintenance therapy did not have a statistically significantly difference in overall survival (HR 0.93, 95% CI 0.87 to 1.00; 3,687 patients) or progression-free survival (HR 0.98, 95% CI 0.91 to 1.06; 2,783 patients). There was substantial heterogeneity in both analyses (I2=60% for overall survival and I2=71% for progression-free survival).
Drug subgroups: Compared with control, maintenance therapy with interferon-gamma or other biological agents did not have a statistically significantly difference for overall survival, but there was a statistically significant benefit in overall survival with maintenance chemotherapy (HR 0.89, 95% CI 0.81 to 0.98; I2=70%; n=1,727 patients) and interferon-alpha (HR 0.78, 95% CI 0.64 to 0.96; I2=0%; n=488 patients). Using a random-effects meta-analysis did not alter the results for interferon-alpha, but the results were no longer significant for chemotherapy (HR 0.87, 95% CI 0.72 to 1.06). Compared with control, the no maintenance therapy drug group had a statistically significantly difference for progression-free survival.
Compliance: The percentage of patients who stopped maintenance therapy due to adverse events was higher with interferons and other biological agents compared with chemotherapy.
There was no evidence of publication bias.