BackgroundThree multicenter, randomized, placebo-controlled Phase III trials of taxane (T), or capecitabine (Cape), or anthracycline (Anth) chemotherapy plus or minus bevacizumab (B) established that the addition of B improves progression-free survival (PFS). Outcomes in clinically important subsets are important to demonstrate the consistency of treatment effect and may guide physicians when considering treatment options for patients. Here we compare various clinically relevant subgroups across three studies to assess the activity of B in patients for these subgroups.MethodsResults for PFS based upon investigator assessments were used from all trials. Kaplan-Meier methodology was used to estimate median PFS for chemo+placebo and chemo+B for patient subgroups from the E2100, AVADO, and RIBBON-1 studies. For the overall study results, stratified hazard ratios (HRs) are presented with the same stratification factors as the variables that were used for the randomization, while unstratified HRs are presented here for the subgroups.ResultsIn all 3 studies we observed an improvement in PFS upon addition of B to chemotherapy. For patients with triple-negative (ER-, PR-, HER2-) tumors, the addition of B led to an increase in median PFS (mPFS) from 4.7 mo to 10.2 mo (HR=0.45; 95% confidence interval [CI], 0.33-0.61) in E2100, from 6.0 to 8.1 mo in the AVADO 15 mg/kg B arm (HR=0.60, 95% CI, 0.39-0.92); from 4.2 to 6.1 mo in the RIBBON-1 Cape cohort (HR=0.72, 95% CI, 0.49-1.06); and from 8.2 to 14.5 mo in the RIBBON-1 T/Anth cohort (HR=0.78, 95% CI, 0.53-1.15).For patients ≥65 yr, the addition of B led to an increase in mPFS from 7.4 to 10.4 mo (HR=0.69, 95% CI, 0.46-1.03) in E2100, from 7.6 to 8.4 mo in the AVADO 15 mg/kg B arm (HR=0.62, 95% CI, 0.36-1.08); from 6.2 to 9.1 mo in the RIBBON-1 Cape cohort (HR=0.69, 95% CI, 0.47-1.02); and from 8.5 to 10.1 mo in the RIBBON-1 T/Anth cohort (HR=0.83, 95% CI, 0.52-1.34).For patients who had received prior adjuvant T, the addition of B led to an increase in mPFS from 4.4 to 13.3. mo in E2100 (HR=0.29; 95% CI, 0.19-0.46), 6.6 to 8.5 mo in the AVADO 15 mg/kg B arm (HR=0.42; 95% CI, 0.23-0.77), 4.2 to 8.7 mo in the RIBBON-1 Cape cohort (HR=0.62; 95% CI, 0.45-0.84); and from 6.7 to 9.1 mo in the RIBBON-1 T/Anth cohort (HR=0.65; 95% CI, 0.39-1.09).ConclusionsAlthough the addition of bevacizumab consistently improved mPFS across a number of clinically relevant subsets, regardless of the chemotherapy backbone used, absolute improvements in HRs and median PFS varied within subsets and across the three trials. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 207.