A phase I trial of combination trastuzumab, lapatinib, and bevacizumab in patients with advanced cancer.

ABSTRACT:

Purpose

Preclinical data indicate that combination HER2-directed and anti-VEGF therapy may bypass resistance to trastuzumab. A phase I trial was performed to assess safety, activity, and correlates.

Experimental design

Patients with advanced, refractory malignancy were enrolled (modified 3 + 3 design with expansions for responding tumor types). Patients received lapatinib daily for 21 days, and bevacizumab and trastuzumab every 3 weeks. Correlates included HER2 extracellular domain levels (ECD) and single nucleotide polymorphisms (SNPs).

Results

Ninety-four patients were treated (median = four prior systemic therapies). The most common related adverse events ≥ grade 2 were diarrhea (n = 33, 35 %) and hypertension (n = 10, 11 %). The recommended phase 2 dose was trastu

SUBMITTER: Falchook GS 

PROVIDER: S-EPMC4297242 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature