A Phase I Study of Alpelisib in Combination with Trastuzumab and LJM716 in Patients with PIK3CA-Mutated HER2-Positive Metastatic Breast Cancer.

ABSTRACT:

Purpose

Activating mutations in PIK3CA promote resistance to HER2-targeted therapy in breast cancer; however, inhibition of PI3K alone leads to escape via feedback upregulation of HER3. Combined inhibition of HER2, HER3, and PI3K overcomes this mechanism preclinically.

Patients and methods

This phase I study investigated the MTD of alpelisib given in combination with trastuzumab and LJM716 (a HER3-targeted antibody) in patients with PIK3CA-mutant HER2-positive (HER2⁺) metastatic breast cancer (MBC) using the continual reassessment method. Secondary analyses included efficacy and exploratory correlative studies.

Results

Ten patients were treated initially with daily alpelisib (arm A). Grade ≥3 adverse events seen in ≥2 patients included diarrhe

SUBMITTER: Jhaveri K 

PROVIDER: S-EPMC8282678 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature