119O - Event-free survival (EFS), overall survival (OS), and safety of adding veliparib (V) plus carboplatin (Cb) or carboplatin alone to neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) after ≥4 years of follow-up: BrighTNess, a randomized phase III trial

Background

In BrighTNess, adding Cb with or without V to neoadjuvant chemotherapy significantly improved pathological complete response (pCR) with an acceptable safety profile in operable TNBC. We report EFS, OS, and second malignancies ≥4 years postsurgery.

Methods

Women with untreated stage II/III TNBC were randomized (2:1:1) to A) paclitaxel (P) 80 mg/m² (weekly, 12 doses) + Cb area under the curve 6 mg/mL (every 3 weeks, 4 cycles) + V 50 mg orally twice a day (PCbV); B) P + Cb + V placebo (PCb); or C) P + Cb/V placebo (P). All patients (pts) then received 4 cycles of doxorubicin + cyclophosphamide every 2–3 weeks. The primary (pCR) and secondary (EFS and OS) endpoints used a fixed testing procedure that ordered PCbV vs P, then PCbV vs PCb. Efficacy was assessed in all randomized pts and safety in all who received ≥1 dose. In primary pCR analyses, PCbV was superior to P but not PCb, so subsequent secondary analyses are descriptive with nominal P values.

Results

Overall, 634 pts were randomized to PCbV (n=316), PCb (n=160), and P (n=158). Median follow-up time was 4.5 years. Hazard ratio (HR) for EFS with PCbV vs P was 0.63 (95% confidence interval [CI] 0.43‒0.92, P=0.016) and 1.12 (95% CI 0.72‒1.72, P=0.620) for PCbV vs PCb. In post hoc analysis, HR for EFS with PCb vs P was 0.57 (95% CI 0.36‒0.91, P=0.018). Deaths occurred in 38/316 (12%) with PCbV, 16/160 (10%) with PCb, and 22/158 (14%) with P. HR for OS was 0.82 (95% CI 0.48‒1.38, P=0.452) for PCbV vs P, 1.25 (95% CI 0.70−2.24, P=0.455) for PCbV vs PCb, and 0.63 (95% CI 0.33−1.21, P=0.166) for PCb vs P. See table for myelodysplastic syndromes (MDS) and second malignancies. Table: 119O

Myelodysplastic syndromes and selected second cancers

^aPatients who received ≥1 dose.^b Standardized Medical Dictionary for Regulatory Activities (MedDRA) query.Cb, carboplatin; P, paclitaxel; V, veliparib.

Conclusions

Adding Cb to P improved pCR and EFS without increasing MDS or acute myeloid leukemia. Addition of V did not impact pCR or EFS. Mortality rate was low, but numerically higher with P than PCbV and PCb.

Clinical trial identification

NCT02032277.

Editorial acknowledgement

Medical writing support was provided by Chun Zhou, PhD, of Fishawack Health, and was funded by AbbVie Inc.

Legal entity responsible for the study

AbbVie Inc.

Funding

AbbVie Inc. funded this study; contributed to its design, data collection, analysis, and interpretation of the data; and participated in the writing, review, and approval of the abstract. All authors had access to relevant data. No honoraria or payments were made for authorship.

Disclosure

S. Loibl: Financial Interests, Institutional, Research Grant: AbbVie, Amgen, AstraZeneca, Celgene, Daiichi-Sankyo, Immunomedics, Novartis, Pfizer, Roche, Cepheid; Other, Personal, Research Grant: Pfizer, Novartis, Immunomedics, SeaGen, Roche; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Novartis, Pfizer, Roche; Financial Interests, Personal, Invited Speaker: Prime/Medscape; Financial Interests, Institutional, Advisory Board: AbbVie, Amgen, AstraZeneca, Celgene, Pfizer, Roche, Seattle Genetics, Merck KG, Eirgenix, DSI, BMS, Lilly, GSK, Pierre Fabre; Financial Interests, Personal, Invited Speaker, Lectures: Chugai; Financial Interests, Institutional, Writing Engagements, Medical writing role: AbbVie, Daiichi-Sankyo, Novartis, Pfizer, and Roche; Financial Interests, Personal, Full or part-time Employment, CEO: GBG Forschungs GmbH; Financial Interests, Institutional, Royalties, Ki67: VM Scope GmbH; Other, Institutional, Royalties, EP14153692.0: Patent; Non-Financial Interests, Personal, Principal Investigator: PI Aphinity; Other, Personal, Member of the Board of Directors: BIG; Other, Personal, Member: AGO, DKG, ASCO, ESMO; Financial Interests, Personal, Invited Speaker: Prime/Medscape. W. Sikov: Non-Financial Interests, Personal, Other, unpaid Member of Steering Committee: AbbVie. J. Huober: Financial Interests, Personal, Research Grant: Celgene, Hexal, and Novartis; Financial Interests, Personal, Other, Honoraria: AbbVie, AstraZeneca, Celgene, Eisai, Lilly, MSD, Novartis, Pfizer, and Roche; Financial Interests, Personal, Advisory Role, Consulting and Advisory role: AbbVie, AstraZeneca, Celgene, Lilly, Hexal, MSD, Novartis, and Roche; Financial Interests, Personal, Other, Travel expenses: Celgene, Daiichi, Novartis, Pfizer, and Roche. H.S. Rugo: Financial Interests, Institutional, Research Grant, Research support for clinical trials through the University of California: AstraZeneca, Boehringer Ingelheim, Daiichi, Eisai, Genentech, Immunomedics, Lilly, Macrogenics, Merck, Novartis, Odonate, Pfizer, Polyphor, Seattle Genetics, and Sermonix; Financial Interests, Personal, Other, Honoraria: Mylan, Puma, and Samsung. J. O'Shaughnessy: Financial Interests, Personal, Advisory Role, Honoraria for consulting and/or advisory boards: AbbVie, Agendia, and Amgen Biotechnology, Aptitude Health, AstraZeneca, Bayer, Bristol Myers Squibb, Celgene Corporation, Clovis Oncology, Daiichi Sankyo, Eisai, G1 Therapeutics, Genentech, Gilead Sciences, GRAIL, Halozyme Therapeutics, Heron Therapeutics. D. Maag: Financial Interests, Personal, Full or part-time Employment: AbbVie; Financial Interests, Personal, Stocks/Shares, may hold stock or options: AbbVie. M. Untch: Financial Interests, Personal, Advisory Board, Lectures and advisory boards: AbbVie, Agendia, Amgen, AstraZeneca, BioNTech, BMS, Celgene, Daiichi-Sankyo, Eisai, GSK, Jansen Cilag, Johnson & Johnson, Lilly, Molecular Health, MSD, Mundipharma, Myriad, Novartis, Pfizer, Pierre Fabre, Roche, and Seagen; Financial Interests, Personal, Other, Consulting: AbbVie. M. Golshan: Non-Financial Interests, Personal, Other, unpaid Member of Steering Committee: AbbVie. O. Metzger: Financial Interests, Personal, Other, Consulting: AbbVie and G1 Therapeutics; Financial Interests, Personal, Research Grant: AbbVie, Genentech, Pfizer, and Roche; Financial Interests, Personal, Other, Travel expenses: AbbVie and Group Oncoclinicas; Non-Financial Interests, Personal, Advisory Board, Uncompensated co-chair of advisory board: Pfizer. M. Dunbar: Financial Interests, Personal, Full or part-time Employment: AbbVie; Financial Interests, Personal, Stocks/Shares, may hold stock or options: AbbVie. W.F. Symmans: Financial Interests, Personal, Stocks/Shares, Founder shares: Delphi Diagnostics; Financial Interests, Personal, Proprietary Information, Intellectual property: Delphi Diagnostics; Financial Interests, Personal, Stocks/Shares, Public Company shares: Eiger Biopharmaceuticals and IONIS Pharmaceuticals; Financial Interests, Personal, Advisory Board, Compensated advisory boards: Merck; Non-Financial Interests, Personal, Advisory Board, Uncompensated advisory boards: Delphi Diagnostics and Roche. C. Geyer: Financial Interests, Personal, Other, Travel funding: AstraZeneca, Daiichi-Sankyo, Genentech, and Roche; Financial Interests, Personal, Writing Engagements, Medical writing role: AbbVie and Roche; Non-Financial Interests, Personal, Advisory Board, Uncompensated advisory board: Daiichi-Sankyo, Genentech, Roche, and Seattle Genetics; Financial Interests, Personal, Advisory Board, Compensated advisory boards: Exact Sciences; Non-Financial Interests, Personal, Other, Uncompensated consulting role: Daiichi-Sankyo; Financial Interests, Personal, Other, Compensated consulting role: Athenex. All other authors have declared no conflicts of interest.