VELIA

Background

Phase III RCT (VELIA/GOG-3005). 1,140 patients with newly diagnosed stage III-IV high-grade serous ovarian cancer, all histologies (unselected for BRCA or HRD). 3-arm design: (1) concurrent + maintenance veliparib (veliparib throughout), (2) concurrent veliparib only + maintenance placebo, (3) placebo throughout. Carboplatin AUC 6 + paclitaxel 175 mg/m² (6 cycles). Concurrent veliparib/placebo: 150 mg BID days 1–21 per cycle. Maintenance veliparib (arm 1): 400 mg BID × 30 cycles. Veliparib is a PARP inhibitor with weaker PARP trapping vs olaparib/niraparib. Primary comparison: veliparib-throughout vs placebo-throughout.

Interventions and follow up

Arm A: Veliparib throughout (concurrent 150 mg BID + maintenance 400 mg BID) + carboplatin + paclitaxel
Arm B: Veliparib concurrent only (150 mg BID) then placebo maintenance + carboplatin + paclitaxel
Arm C: Placebo throughout + carboplatin + paclitaxel
Primary endpoint: PFS (veliparib-throughout vs placebo-throughout)
mFollow up: 28.2 month

Results

Median PFS — veliparib throughout vs placebo: 23.5 vs 17.3 months, HR 0.68 (95% CI 0.56–0.83), P<.001
PFS in BRCA-mutated subgroup: 34.7 vs 22.0 months, HR 0.44, P<.001
PFS in BRCA wild-type HRd subgroup: 31.9 vs 20.5 months, HR 0.57, P<.001
PFS in BRCA wild-type HRp subgroup: 15.0 vs 11.5 months, HR 0.81, P=.19 — not significant

Adverse events

Main adverse events: Grade ≥3 anemia: 27% (veliparib throughout) vs 19% (placebo). Neutropenia: 61% vs 54%. Grade ≥3 nausea: 15% vs 5%. Discontinuation: 20% (veliparib throughout) vs 7% (placebo). More GI toxicity concurrent with carboplatin + paclitaxel compared to other PARP inhibitor trials where PARP inhibitor given after chemo.

Conclusions

Veliparib added throughout chemotherapy and as maintenance significantly improved PFS vs placebo in newly diagnosed ovarian cancer (HR 0.68), with greatest benefit in BRCA-mutated (HR 0.44) and HRd (HR 0.57) patients, and no significant benefit in HRp patients.

Key Limitations

Key Limitations: Veliparib has the weakest PARP trapping of the approved PARP inhibitors — less potent than olaparib or niraparib. Adding veliparib during chemotherapy (not just as maintenance) increased toxicity without clear advantage over maintenance-only approaches (SOLO1, PRIMA). The concurrent + maintenance design makes it impossible to separate contributions of concurrent vs maintenance components. No FDA approval for this indication; the concurrent approach is not standard.

Clinical Context

VELIA confirmed PARP inhibitor benefit in ovarian cancer is largest in BRCA-mutated and HRd tumors and minimal in HRp tumors — consistent with SOLO1, PRIMA, and PAOLA-1. However, veliparib is not FDA-approved for ovarian cancer; olaparib (SOLO1, PAOLA-1) and niraparib (PRIMA) dominate clinical practice as first-line maintenance. VELIA provided important biological confirmation of biomarker-based PARP inhibitor sensitivity.

References

References: Coleman RL et al, N Engl J Med 2019 (VELIA)