Background

This phase III randomized placebo (PL) controlled multinational trial evaluated whether progression-free survival (PFS) is increased when V is added to front-line carboplatin and paclitaxel (CP) and continued as maintenance in newly diagnosed HGSC pts considering BRCA mutations (m), homologous recombination deficiency (HRD), and neoadjuvant chemotherapy (NACT) utilization.

Methods

Previously untreated Stage III-IV HGSC pts were to receive 6 cycles (21-d interval) of CP using 3-wkly or wkly paclitaxel, following primary cytoreduction or NACT with interval cytoreduction. V or PL was administered during CP (150 mg BID PO) and as maintenance (400 mg BID for 30 cycles). Randomization was 1:1:1, stratified by Stage III vs IV, residual disease and regimen, region, and gBRCA status: Arm 1: CP + PL then PL maintenance Arm 2: CP + V then PL maintenance Arm 3: CP + V then V maintenance Primary endpoints were PFS (Kaplan-Meier) in Arm 3 vs 1 using hierarchical testing in BRCAm, HRD (incl. BRCAm), and whole populations by log-rank tests. Secondary endpoints were PFS (Arm 2 vs 1), overall survival, and disease related symptom scores. Germline and tissue BRCAm and HRD were determined by central testing.

Results

1140 pts were enrolled with 26% in BRCAm and 55% in HRD populations. Efficacy results summarized in Table. Relative CP dose intensities were similar between arms. Grade 3-4 adverse events (AE; Arm 3 vs 1) were similar during CP with the exception of thrombocytopenia (27% vs 8%); during maintenance, any grade 3-4 AE was higher for V treatment (45% vs 32%) but serious AEs were similar (17% vs 19%).Table:

LBA3

Conclusions

V added to front-line CP and continued as monotherapy maintenance significantly extended PFS in all women with newly diagnosed HGSC without selection according to BRCAm or HRD status, or response to CP. Observed toxicities were consistent with known V safety profile.

Clinical trial identification

NCT02470585.

Editorial acknowledgement

Medical writing support was provided by Ana Mrejeru, Ph.D., of AbbVie.

Legal entity responsible for the study

AbbVie.

Funding

AbbVie.

Disclosure

R.L. Coleman: Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Clovis Oncology; Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Genentech/Roche; Advisory / Consultancy, Research grant / Funding (self): Esperance; Advisory / Consultancy: NCCN; Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: AstraZeneca/MedImmune; Advisory / Consultancy: Genmab; Advisory / Consultancy: GamaMabs Pharma; Advisory / Consultancy: Tesaro; Advisory / Consultancy, Research grant / Funding (self): OncoMed; Advisory / Consultancy: Sotio; Advisory / Consultancy: Oncolytics; Advisory / Consultancy: AbbVie/Stemcentrx; Research grant / Funding (self), Travel / Accommodation / Expenses: Merck; Research grant / Funding (self), Travel / Accommodation / Expenses: Array Biopharma; Travel / Accommodation / Expenses: Research to Practice; Travel / Accommodation / Expenses: GOG; Travel / Accommodation / Expenses: Sotio; Travel / Accommodation / Expenses: Vaniam Group; Research grant / Funding (self): Johnson & Johnson; Research grant / Funding (self): Abbott/AbbVie. G.F. Fleming: Research grant / Funding (self): Corcept Therapeutics; Research grant / Funding (self): AbbVie; Research grant / Funding (self): Genentech; Research grant / Funding (self): Tesaro; Research grant / Funding (self): Syndax; Research grant / Funding (self): Forty Seven; Research grant / Funding (self): Iovance; Research grant / Funding (self): Syros; Research grant / Funding (self): Astex; Research grant / Funding (self): Merck. K.D. Steffensen: Honoraria (self), Research grant / Funding (institution): AstraZeneca; Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AbbVie. M. Friedlander: Advisory / Consultancy: AbbVie; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: Takeda; Research grant / Funding (self): BeiGene. A. Okamoto: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Chugai; Honoraria (self): MSD; Research grant / Funding (self): Kaken; Research grant / Funding (self): Mochida; Research grant / Funding (self): Kissei; Research grant / Funding (self): Pfizer. K. Moore: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Genentech/Roche; Advisory / Consultancy, Research grant / Funding (institution): Immunogen; Advisory / Consultancy, Research grant / Funding (institution): Advaxis; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Non-remunerated activity/ies: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Clovis Oncology; Advisory / Consultancy, Research grant / Funding (institution): Tesaro; Advisory / Consultancy: VBL Therapeutics; Advisory / Consultancy: Janssen Oncology; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy: Aravive; Advisory / Consultancy: Samumed; Advisory / Consultancy: OncoMed; Advisory / Consultancy: Pfizer/EMD Serono ; Advisory / Consultancy: Eisai; Research grant / Funding (institution): PTC Therapeutics; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Lilly Foundation; Research grant / Funding (institution): Regeneron; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Verastern; Research grant / Funding (institution): Agenus; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Forty Seven; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Novogen. N. Ben-Baruch: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Eli Lilly; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Novartis; Research grant / Funding (self): AbbVie. T.L. Werner: Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Roche/Genentech; Research grant / Funding (institution): Mirati Therapeutics; Research grant / Funding (institution): Tesaro; Research grant / Funding (institution): Clovis; Research grant / Funding (institution): AstraZeneca. A. Oaknin: Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Travel / Accommodation / Expenses: Pharmamar; Advisory / Consultancy, Travel / Accommodation / Expenses: Clovis Oncology; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Immunogen ; Advisory / Consultancy: Genmab. J. Nam: Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Zeria Pharmaceutical Co.. C.A. Leath III: Honoraria (self), Research grant / Funding (institution): Mateon Therapeutics; Advisory / Consultancy, Research grant / Funding (institution): Celsion; Advisory / Consultancy: Unleash Immuno Oncolytics; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Plexxikon; Research grant / Funding (institution): Tesaro; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Roche/Genentech; Advisory / Consultancy, Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Syros; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy: Eisai. S. Nicum: Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: Roche; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy, Travel / Accommodation / Expenses: Tesaro. D. Cella: Advisory / Consultancy: AbbVie; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy: GlaxoSmithKline; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: Astellas; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: PledPharma; Advisory / Consultancy: Puma Biotechnology; Research grant / Funding (institution), Travel / Accommodation / Expenses: Ipsen; Shareholder / Stockholder / Stock options: FACIT.org; Research grant / Funding (institution): Genentech. D.M. Sullivan: Shareholder / Stockholder / Stock options, Full / Part-time employment: AbbVie. P.J. Ansell: Shareholder / Stockholder / Stock options, Full / Part-time employment: AbbVie. M. Dinh: Shareholder / Stockholder / Stock options, Full / Part-time employment: AbbVie. C. Aghajanian: Advisory / Consultancy, Research grant / Funding (institution): Clovis Oncology; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Mateon Therapeutics; Advisory / Consultancy: Immunogen; Research grant / Funding (institution): Genentech/Roche; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Cerulean Pharma; Advisory / Consultancy: Eisai/Merck. M.A. Bookman: Non-remunerated activity/ies, Member, international protocol steering committee (AbbVie GOG3005): AbbVie; Non-remunerated activity/ies, protocol steering committee: Genentech-Roche; Non-remunerated activity/ies, protocol steering committee: ARAVIVE; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Merck; Advisory / Consultancy: AstraZeneca. All other authors have declared no conflicts of interest.