Pistilli B, et al. - A phase Ib study in patients with trastuzumab-resistant, human epidermal growth factor receptor-2- (HER2)-positive advanced breast cancer defined the recommended phase II dose of buparlisib as 100 mg/day in combination with 2 mg/kg weekly trastuzumab, and reported preliminary signs of clinical activity. In this work, the results from the phase II portion were reported. As a chemotherapy-free regimen, buparlisib plus trastuzumab showed an acceptable safety profile. However, in patients with heavily pretreated, trastuzumab-resistant HER2-positive breast cancer, and in patients with progressive brain metastases also receiving capecitabine, the regimen showed limited efficacy.

Methods

• Buparlisib plus trastuzumab was administered to patients with trastuzumab-resistant, HER2-positive advanced breast cancer.
• Safety/tolerability and antitumour activity were included as the study endpoints.
• Extension of the study was performed to include a phase Ib dose-escalation phase, in which patients with progressive brain metastases also received capecitabine.

Results

• The most common (≥ 30%) all-grade adverse events (AEs) observed in 50 patients treated with buparlisib and trastuzumab in the phase II portion were diarrhoea (54%), nausea (48%), decreased appetite, increased alanine aminotransferase (36% each), increased aspartate aminotransferase (34%), fatigue, rash (32% each), cough and hyperglycemia (30% each).
• Complete response was evident in 1 (2%) patient and confirmed partial responses were evident in 4 (8%) patients [PR; including two patients with phosphatidylinositol 3-kinase (PI3 K) pathway-activated tumours].
• Researchers observed an overall response rate (ORR) of 10%: the primary endpoint (ORR ≥ 25%) was therefore not met.
• In the phase Ib portion, tumour shrinkage to some degree was evident in all patients with measurable brain lesions at baseline; due to low enrollment, maximum tolerated dose of buparlisib in combination with trastuzumab and capecitabine was not determined.