In the phase 3 VELIA study, patients with high-grade serous ovarian cancer were randomized to 1 of 3 treatment options: carboplatin/paclitaxel (CP) plus placebo followed by placebo maintenance, CP plus veliparib (VEL) followed by placebo maintenance, or CP plus VEL followed by VEL maintenance. This study demonstrated a significant improvement in progression-free survival (PFS) for patients treated with CP and VEL versus those treated with CP alone. Investigators were able to choose to deliver paclitaxel one of two ways—either 175 mg/m2 intravenously every 3 weeks (Q3W) or 80 mg/m2 dose dense (DD) weekly. This exploratory analysis of the VELIA data evaluates PFS and safety by dosing regimen of paclitaxel.
Patient randomization was stratified by paclitaxel regimen, extent of residual disease, disease stage, and region. Treatment included combination therapy given for six 21-day cycles followed by 30 cycles of VEL or placebo maintenance. Of the 1132 patients in the evaluable population, 52% received DD paclitaxel, whereas 48% received Q3W paclitaxel. Median dose intensity varied somewhat across treatment arms: 95% to 99% with Q3W paclitaxel and 84% to 95% with DD paclitaxel. DD paclitaxel was associated with longer PFS when compared with Q3W paclitaxel (median, 20.5 vs 15.7 months; hazard ratio, 0.77; 95% confidence interval, 0.66-0.89). This was also true in subgroup analyses by ethnicity, for those with wild-type BRCA, and regardless of homologous recombination deficiency status. In patients with mutated BRCA, PFS did not vary by paclitaxel regimen. Patients with BRCA wild-type and homologous recombination–proficient tumors showed the greatest difference in PFS with DD paclitaxel versus Q3W paclitaxel. Regardless of paclitaxel regimen, those receiving VEL throughout their treatment achieved longer PFS than those who received CP alone.
The “as-treated” safety population for this study included 1124 patients. Those who received DD paclitaxel experienced more frequent grade 3/4 adverse events (AEs) than those who received Q3W paclitaxel. In the CP-alone arm, 90% of those receiving DD paclitaxel experienced grade 3/4 AEs versus 63% of those receiving Q3W paclitaxel. In the CP plus VEL followed by placebo maintenance arm, grade 3/4 AEs were experienced by 94% of those receiving DD paclitaxel versus 80% of those receiving Q3W paclitaxel. Finally, in the CP plus VEL followed by VEL maintenance arm, grade 3/4 AEs were experienced by 94% of those receiving DD paclitaxel versus 82% of those receiving Q3W paclitaxel. When analyzing hematologic toxicities specifically, DD paclitaxel was associated with a higher frequency of grade 3/4 events versus Q3W paclitaxel.
The authors concluded that in patients with newly diagnosed high-grade serous ovarian cancer, DD paclitaxel, regardless of treatment with VEL, was associated with longer PFS overall and also in biomarker-negative subgroups. Furthermore, DD paclitaxel was also associated with a higher frequency of grade 3/4 AEs, including hematologic toxicities, versus paclitaxel Q3W.
Abstract and Poster 818P. ESMO 2020. September 19-21, 2020. Veliparib with carboplatin and paclitaxel in frontline high-grade serous ovarian cancer (HGSOC): efficacy and safety of paclitaxel weekly and every 3 weeks in the VELIA study.
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