Abstract PD5-8: Phase I clinical trial of neoadjuvant BIBF1120 plus weekly paclitaxel (P) in early HER-2 negative breast cancer. CNIO-BR-01-2010/GEICAM 2010-10 study

Abstract

Abstract Background: BIBF1120 has shown promising preclinical efficacy in breast cancer, and weekly paclitaxel (P) is a standard of care in BC. We designed a phase I/II trial of BIBF 1120 plus weekly P in early breast cancer, and report here the phase I part of the trial. The recommended dose has been determined and, additionally, efficacy has been assessed. Methods: Eligible patients had pathologically confirmed HER2 negative stage II or IIIA untreated breast cancer. BIBF1120 and P were administered at the following dose levels (DL): DL1: BIBF1120 150 mg bid p.o. days 1-21 plus P 80 mg/ m2 iv on days 1, 8 and 15 q21 days; DL2: BIBF1120 200 mg bid p.o. days 1-21 plus P same dose as level 1, q21 days. On the P-infusion day, the morning BIBF1120 dose was skipped to avoid potential PK interactions. A 3+3 escalation scheme with common dose-limiting toxicity (DLT) definitions was adopted. Four three-week cycles of BIBF1120 plus P followed by 4 AC cycles were administered. Surgery was planned 4-5 weeks after the last AC dose. We report the phase I part results of the phase I/II trial. Results: 9 patients have been evaluated for toxicity (6 patients in DL1 and 3 in DL2). Median age was 47.6 years (38.1-66.7) and 8 patients (89%) were premenopausal; median tumour size was 3.0 cm (2.7-6.5), 6 patients (66.7%) had stage II disease and 3 patients (33.3%) stage III. Seven cases (78%) were hormone-receptor (HR) positive and 2 (22%) negative. Two patients had DLT at DL2: ALT grade 3 (one patient); and ALT grade 4, AST grade 3 and GGT grade 3 (one patient). One case was reduced to DL1 and one withdrew consent after 7 days of treatment. Main related toxicities during treatment: DL1 GGT grade 2 (16.7%), hypertension grade 2 (50%), DL2 ALT grade 3 (33.3%), AST grade 3 (33.3%), bilirubin grade 2 (33.3%), GGT grade 2/3 (100%). Toxicities observed at DL2 were reversible by withholding BIBF1120 administration. Eight patients were evaluable for efficacy after surgery and have been assessed for pathological response: 2/2 (100%) HR(-) and 2/6 (33%) HR(+) patients, for a total of 4/8 (50%) patients, pCR defined as Miller&Payne score scale of 5. Three of these received DL1 and 1 DL2. A total of 6 patients (75%) underwent conservative surgery. Conclusions: Concomitant administration in early stage HER-2 negative breast cancer of BIBF1120 plus P at DL1 was manageable and had mild toxicity, showing remarkable efficacy specially in triple-negative breast cancer. BIBF1120 150 mg bid plus weekly P 80mg/m2 is the recommended dose for the ongoing phase II part of study CNIO-BR-01-2012/GEICAM 2010-10 with an enrolment target of 130 patients, of which 81 have been already recruited. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr PD5-8.