neophoebe: neoadjuvant trastuzumab + bkm120 in combination with weekly paclitaxel in her2-positive primary breast cancer

Conditions: HER2-positive Newly Diagnosed, Primary Breast Cancer

Summary: this randomized, parallel cohort, two stage, double-blind, placebo-controlled study evaluated the oral pi3k inhibitor bkm120 in combination with trastuzumab and paclitaxel in her2-positive, pik3ca wild-type and pik3ca mutant primary breast cancer prior to surgery (neo-adjuvant setting).

neophoebe evaluated the efficacy (as defined by pcr) of bkm120 (an oral pi3k inhibitor) in combination with trastuzumab and paclitaxel in a randomized, placebo-controlled, neo-adjuvant study in women diagnosed with primary breast cancer \>1.5 cm (by us or mri) with centrally confirmed her2 overexpression or amplification, who have not previously undergone treatment for invasive breast cancer. prior to the initiation of paclitaxel, there was a 6-week "biologic window" with trastuzumab plus bkm120 or placebo only. the study was conducted separately in two cohorts (pik3ca mutated and pi3k3ca wild-type) using a two-stage approach. within each cohort patients were randomized into one of the following treatment arms: arm 1: bkm120 plus trastuzumab for 6 weeks followed by bkm120 and trastuzumab plus weekly paclitaxel for an additional 12 weeks. arm 2: bkm120 placebo plus trastuzumab for 6 weeks followed by bkm120 placebo plus trastuzumab plus weekly paclitaxel for an additional 12 weeks. after completion of study treatment, patients were to have undergone definitive surgery.

Eligibility criteria:
inclusion criteria: * patient had provided a signed study icf prior to any screening procedure * patient was a female ≥ 18 years of age * patient has an ecog performance status of 0-1 * patient has a unilateral (multifocal or multicentric disease allowed), histologically confirmed, newly diagnosed early breast cancer \>2cm by clinical examination and/or \>1.5 cm confirmed by ultrasound or by mri * patient has tumor tissue available for central review of er, her2 and pi3k status with centrally confirmed her2-positive disease and known pi3kca mutation status * patient has adequate bone marrow, renal and liver function * patient is able to swallow and retain oral medication exclusion criteria: * patient has received prior systemic treatment for currently diagnosed disease * patient has a known contraindications, hypersensitivity or intolerance to trastuzumab, paclitaxel or products containing cremophor * patient has bilateral breast cancer or metastatic disease or inflammatory breast cancer * lvef below 50% as determined by muga scan or echo * patient has active cardiac disease or a history of cardiac abnormalities as defined in the protocol * patient has impairment of gastrointestinal (gi) function or gi disease that may significantly alter the absorption of bkm120 * patient is currently receiving warfarin or other coumarin derived anti-coagulants * patient is currently receiving chronic treatment with corticosteroids or another immunosuppressive agents (standard premedication for paclitaxel and local applications allowed) * patient is currently receiving treatment with drugs known to be strong inhibitors or inducers of cyp3a * patient has certain scores on an anxiety and depression mood questionnaires * pregnant or nursing (lactating) women or patients not willing to apply apply highly effective contraception as defined in the protocol

Keywords: her2 breast cancer neoadjuvant pi3k inhibitor first line chemotherapy trastuzumab gbg solti big