Trastuzumab and Pertuzumab in Patients with Non-Breast/Gastroesophageal HER2-Amplified Tumors: Results from the...

Area of Science:

• Oncology
• Genomics
• Clinical Trials

Background:

• The NCI-MATCH trial investigated targeted therapies in advanced cancers with specific genomic alterations.
• Arm J (EAY131-J) focused on the combination of trastuzumab/pertuzumab (HP) in patients with HER2-amplified tumors.

Purpose of the Study:

• To evaluate the efficacy of trastuzumab/pertuzumab (HP) in patients with advanced HER2-amplified cancers.
• To determine the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) of HP treatment.

Main Methods:

• Patients with advanced cancer and HER2 amplification (copy number [CN] ≥7) were enrolled.
• Exclusions included prior HER2-directed therapy and specific cancer types (breast/gastroesophageal adenocarcinoma).
• Patients received HP intravenously every 3 weeks until disease progression or toxicity.

Main Results:

• Twenty-five patients were included in the primary efficacy analysis, with a median HER2 CN of 28.
• The confirmed ORR was 12% (3/25 partial responses) in colorectal, cholangiocarcinoma, and urothelial cancers.
• Median PFS was 3.3 months and median OS was 9.4 months; no association between HER2 CN and response was observed.

Conclusions:

• Trastuzumab/pertuzumab (HP) demonstrated activity in a subset of HER2-amplified non-breast/gastroesophageal tumors but did not meet the predefined efficacy benchmark.
• Additional strategies targeting HER2 and resistance pathways are needed, particularly for rare tumor types.