Patients With PIK3CA Mutations Less Likely to Benefit From Dual Anti-HER2 Inhibition

the Cancer Therapy Advisor take:

PIK3CA mutations were identified as possible predictive biomarkers of resistance to dual anti-human epidermal growth factor 2 (HER2) treatment for patients with breast cancer, according to an article published online in the journal The Oncologist.

Participants in this study included 121 patients with breast cancer who were positive for HER2. These patients were randomly assigned to neoadjuvant chemotherapy plus trastuzumab, lapatinib, or both trastuzumab and lapatinib.

The investigators collected pre- and post-treatment samples and evaluated them for HER2, p95-HER2, phosphorylated AKT (pAKT), phosphatase and tensin homolog, Ki67, apoptosis, and PIK3CA mutations.

Results showed 20% of the cases had a mutation in PIK3CA exon 20 or 9. Pathologic complete remission (pCR) rates were determined to be similar in PIK3CA wild-type (33.3%) and PIK3CA-mutated patients (22.7%; P=0.323).

Patients with PIK3CA wild-type tumors who were administered trastuzumab plus lapatinib experienced a higher probability of pCR (48.4% vs. 12.5%; P=0.06).

Furthermore, Ki67, pAKT, and apoptosis mutations were significantly decreased from baseline, as measured from the residual disease. Patients who received the dual anti-HER2 blockade demonstrated significantly greater degrees of Ki67 inhibition.

The gene expression and copy number data analysis revealed that a 50-gene signature specifically predicted pCR induced by lapatinib.