Conditions: HER2-positive Newly Diagnosed, Primary Breast Cancer
Keywords: HER2 breast cancer neoadjuvant PI3K inhibitor first line chemotherapy trastuzumab GBG SOLTI BIG
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 50
Healthy volunteers: no

Brief 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).

Detailed description:
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.

Arms:
arm 1: BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel. arm 2: BKM120 placebo in combination with trastuzumab and paclitaxel

Interventions: intervention 1: BKM120 intervention 2: Trastuzumab intervention 3: Paclitaxel intervention 4: BKM120 Placebo
Intervention descriptions: intervention 1: Neo-adjuvant BKM120 (oral pan-class I PI3K inhibitor, continuous daily dosing). BKM120 was administered orally 100 mg/day. intervention 2: Trastuzumab is a humanized monoclonal antibody directed against the extracellular juxtamembrane domain of the HER2 receptor. Administered 4mg/kg i.v. load followed by 2mg/kg i.v. weekly. intervention 3: Paclitaxel is a cytotoxic agent with proven antitumor activity in a variety of solid tumors. The antitumor activity of paclitaxel is based on tubulin-binding and stabilization of non-functional microtubule bundles, thereby blocking normal mitotic spindle development and subsequent cell division. Administered weekly 80mg/m2 i.v. intervention 4: Neoadjuvant BKM120 placebo Administered orally 100 mg/day.

Protocol document: