818P - 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

Background

The phase III randomised VELIA study (NCT02470585) demonstrated significantly improved progression-free survival (PFS) with carboplatin/paclitaxel (CP) and veliparib (VEL) induction therapy followed by VEL maintenance vs CP alone (HR 0.44; 95% CI 0.28–0.68; Coleman et al., N Engl J Med 2019). Investigators chose between IV P 175 mg/m² every 3 weeks (Q3W), or 80 mg/m² dose-dense (DD) weekly. This exploratory analysis evaluated PFS and safety by P regimen.

Methods

Patients received (1:1:1) CP + placebo followed by placebo maintenance (CP alone), or CP + VEL followed by placebo (VEL combination only), or CP + VEL followed by VEL (VEL throughout). Randomisation was stratified by P regimen and residual disease, disease stage, and region. Combination therapy was given for six 21-day cycles, followed by 30 cycles of VEL/placebo maintenance monotherapy. PFS was analysed using a Cox proportional hazards regression model.

Results

Among evaluable patients (N=1132), 52% received DD P; 48% received Q3W P. Cohorts were balanced for clinical characteristics and molecular signature (BRCA, homologous repair deficiency [HRD]). Median dose intensity ranged from 95%−99% with Q3W P and 84%−94% with DD P across treatment arms. Overall, DD P demonstrated longer PFS vs Q3W P (median: 20.5 vs 15.7 months; hazard ratio [HR] 0.77; 95% CI 0.66–0.89). The table shows effects of P regimen across subgroups and treatment arms. PFS was improved with VEL throughout vs CP alone, irrespective of P regimen. In the as-treated safety population (N=1124), Grade 3/4 adverse events were more frequent with DD P vs Q3W P, with rates of 90% vs 63% with CP alone, 94% vs 80% with VEL combination only, and 94% vs 82% with VEL throughout.

Conclusions

In this exploratory analysis, DD P (+/- VEL) was associated with longer PFS overall and in biomarker-negative subgroups, and more frequent Grade 3/4 haematologic toxicities vs Q3W P in patients with newly diagnosed HGSOC.

Clinical trial identification

NCT02470585.

Editorial acknowledgement

Karen O'Leary, Fishawack Communications.

Legal entity responsible for the study

AbbVie, Inc.

Funding

AbbVie, Inc.

Disclosure

A. Okamoto: Advisory/Consultancy: AstraZeneca, Chugai; Honoraria (self): AstraZeneca, MSD, Chugai; Research grant/Funding (self): Kaken, Mochida, Kissei, Pfizer. G. Fleming: Research grant/Funding (institution): Corcept Therapeutics, AbbVie, Genentech, Tesaro, Sermonix, Syndax, Forty Seven, Iovance, Syros, Astex, Merck; Advisory/Consultancy, Research grant/Funding (self): GSK; Speaker Bureau/Expert testimony: Vaniam Group, Wolters Kluwer; Honoraria (self), Author fees: Wolters Kluwer. M. Bookman: Advisory/Consultancy, Member, international protocol steering committee (AbbVie GOG3005): AbbVie; Advisory/Consultancy: AstraZeneca, Immunogen, Clovis Oncology, Tesaro, Bayer, Merck, Pfizer. K.D. Steffensen: Advisory/Consultancy: AbbVie; Research grant/Funding (institution): AstraZeneca and AbbVie. T. Enomoto: Honoraria (self): AstraZeneca, MSD, Chugai. D.M. O'Malley: Honoraria (self), Advisory/Consultancy, Personal fees (consulting, steering committee and/or advisory boards) and research funding: AstraZeneca, Clovis, Tesaro, Immunogen Ambry, Janssen/J&J, AbbVie, Regeneron, Amgen, Novocure, Genentech/Roche, GOG Foundation, Agenus, Iovance, Eisai; Advisory/Consultancy: Genelux; Research grant/Funding (self): VentiRx, Array Biopharma, EMD Serono, Ergomed, Ajinomoto Inc., Ludwig Cancer Research, Stemcentrx, Inc., Cerulean Pharma, Bristol-Myers Squibb Co., Serono Inc., Tracon Pharmaceuticals, Yale University, New Mexico Cancer Care Alliance, INC Research, Inc.,. K.S. Tewari: Advisory/Consultancy: Genentech, Clovis, Tesaro; Speaker Bureau/Expert testimony: Roche, Merck, Clovis, Tesaro, AstraZeneca; Research grant/Funding (institution), Contracted Research to Institution: AbbVie. J.N. Barlin: Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca. W. Bradley: Advisory/Consultancy: Celsion, Inovio. K.N. Moore: Advisory/Consultancy: AbbVie, AstraZeneca, Aravive, Eisai, GSK/Tesaro, Genentech/Roche, Immunogen, Merck, Mersana, Tarveda, VBL Therapeutics, Vavotar; Research grant/Funding (institution): PTC Therapeutics, GSK/Tesaro, Merck, Genentech/Roche. J. Chan: Advisory/Consultancy, Speaker Bureau/Expert testimony: AbbVie, Acerta, Aravive, AstraZeneca, Clovis, Eisai, GSK, Merck, Roche. M. Wu: Shareholder/Stockholder/Stock options, Full/Part-time employment, May own stock: AbbVie Inc. H. Hashiba: Shareholder/Stockholder/Stock options, Full/Part-time employment, May own stock: AbbVie. M.H. Dinh: Shareholder/Stockholder/Stock options, Full/Part-time employment, May own stock: AbbVie Inc. R.L. Coleman: Advisory/Consultancy: Clovis Oncology, Genentech/Roche, Esperance, NCCN, AstraZeneca/MedImmune, Genmab, GamaMabs Pharma, Tesaro, OncoMed, Sotio, Oncolytics, AbbVie/Stemcentrx; Travel/Accommodation/Expenses: Merck, AstraZeneca/MedImmune, Array Biopharma, Clovis, Roche/Genentech, Research to Practice, GOG, Sotio, Vaniam Group; Research grant/Funding (self): AstraZeneca/MedImmune, Esperance, OncoMed, Array, Clovis, Johnson & Johnson, Merck, Roche/Genentech, Abbott/AbbVie (principal investigator on VELIA study). C. Aghajanian: Advisory/Consultancy: Clovis Oncology, Tesaro, Mateon Therapeutics, Immunogen, Cerulean Pharma, Eisai/Merck; Research grant/Funding (institution): Genentech/Roche, AbbVie, Clovis Oncology, AstraZeneca. All other authors have declared no conflicts of interest. Table: 818P

PFS subgroup analysis

*Adjusted for treatment arm and stratification factors (residual disease, stage, BRCA status).^†Adjusted for stratification factors.