Abstract
Iniparib is an investigational agent with antitumor activity of controversial mechanism of action. Two previous trials in advanced triple-negative breast cancer (TNBC) in combination with gemcitabine and carboplatin showed some evidence of efficacy that was not confirmed. This phase II randomized neoadjuvant study was designed to explore its activity and tolerability with weekly paclitaxel (PTX) as neoadjuvant treatment in TNBC patients. 141 patients with Stage II–IIIA TNBC were randomly assigned to receive PTX (80 mg/m2, d1; n = 47) alone or in combination with iniparib, either once-weekly (PWI) (11.2 mg/kg, d1; n = 46) or twice-weekly (PTI) (5.6 mg/kg, d1, 4; n = 48) for 12 weeks. Primary endpoint was pathologic complete response (pCR) in the breast. pCR rate was similar among the three arms (21, 22, and 19 % for PTX, PWI, and PTI, respectively). Secondary efficacy endpoints were comparable: pCR in breast and axilla (21, 17, and 19 %); best overall response in the breast (60, 61, and 63 %); and breast conservation rate (53, 54, and 50 %). Slightly more patients in the PTI arm presented grade 3/4 neutropenia (4, 0, and 10 %). Grade 1/2 (28, 22, and 29 %), but no grade 3/4 neuropathy, was observed. There were no differences in serious adverse events and treatment-emergent adverse events leading to treatment discontinuation among the three arms. Addition of iniparib to weekly PTX did not add relevant antitumor activity or toxicity. These results do not support further evaluation of the combination of iniparib at these doses plus paclitaxel in early TNBC.
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This work was fully supported by Sanofi.
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Employment: EJC (Sanofi), IGR (Sanofi); Remuneration: ALC (Roche, Lilly, Pfizer, Novartis), J. Balmaña (AstraZeneca), HR (Roche, Pierre Fabre, AstraZeneca), SGS (Roche, GlaxoSmithKline, Novartis, Teva, Eisai, Celgene); Stock ownership: ALC (MEDSIR ARO), EJC (Sanofi), IGR (Sanofi); Consultant/Advisory Role: ALC (Roche, AstraZeneca, Pfizer), CV (Bristol-Myers Squibb, GlaxoSmithKline, Roche, Novartis), SD (Novartis, Pfizer, Roche), J. Balmaña (AstraZeneca), SGS (AstraZeneca), JG (Novartis), NH (AstraZeneca); Funding: ALC (MEDSIR ARO, Celgene, Roche), SD (Novartis, Pfizer, Roche, Puma, Amgen, AstraZeneca), J. Balmaña (AstraZeneca, Pharmamar), HR (Roche, Amgen, Pierre Fabre), NH (Biomarin), NRR (Roche, Bristol-Myers Squibb, Janssen). All remaining authors have declared no conflicts of interest.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Informed consent was obtained from all individual participants included in the study.
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Clinical trial number: This trial was registered in clinicaltrials.gov (NCT01204125).
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Llombart-Cussac, A., Bermejo, B., Villanueva, C. et al. SOLTI NeoPARP: a phase II randomized study of two schedules of iniparib plus paclitaxel versus paclitaxel alone as neoadjuvant therapy in patients with triple-negative breast cancer. Breast Cancer Res Treat 154, 351–357 (2015). https://doi.org/10.1007/s10549-015-3616-8
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DOI: https://doi.org/10.1007/s10549-015-3616-8