The established dual HER2 blockade of pertuzumab and trastuzumab may be an effective treatment for patients with several types of HER2-amplified cancers, according to a study published by Connolly et al in Clinical Cancer Research.
Background
HER2 receptors control how cells grow and divide. The development of resistance to trastuzumab is a common clinical challenge in oncology, leading to numerous clinical trials seeking improvements for patients.
“It is so important for us to identify treatment approaches that result in high rates of tumor shrinkage while minimizing adverse effects for the patients and maximizing quality of life during the treatment course,” explained lead study author Roisin M. Connolly, MB, BCh, MD, of the University College Cork in Ireland and the Eastern Cooperative Oncology Group–American College of Radiology Imaging Network (ECOG-ACRIN) Cancer Research Group.
The U.S. Food and Drug Administration approved trastuzumab/pertuzumab to treat patients with HER2-positive breast cancer.
The NCI-MATCH (Molecular Analysis for Therapy Choice) precision medicine initiative is one of the first and largest precision oncology trials undertaken globally.
Study Methods and Results
In the single-arm, phase II NCI-MATCH Arm J trial, researchers recruited 35 patients with advanced cancers—other than breast cancer—that had high levels of HER2 gene amplification, which was defined as a copy number of seven or greater. They excluded patients with gastric cancer or gastroesophageal junction adenocarcinoma. After conducting a central evaluation of HER2 gene amplification, the researchers included 25 patients with gynecologic cancer (n = 11), gastrointestinal cancer (n = 11), urothelial carcinoma (n = 2), and head and neck cancer (n = 1) in their primary analysis. They noted that the median age of the patients was 66 years, 56% of them were female, and about 50% of them had received three or more prior therapies.
The confirmed overall response rate in the evaluable patients was 12% (n = 3/25). All three of the patients had a partial response and a different type of cancer: colorectal cancer, cholangiocarcinoma, and urothelial carcinoma.
Further, one of the patients with urothelial carcinoma with an unconfirmed HER2 copy number experienced a partial response. Stable disease was observed in nine patients with cholangiocarcinoma, gynecologic cancer, and colorectal cancer. The trial came just short of meeting the predefined success criteria for the primary endpoint, defined as an overall response rate greater than 16%.
“As the prespecified criteria for efficacy success was not met, it may be that more refined patient selection such as predictive biomarkers or alternative HER2-directed approaches [like] combinations with chemotherapy or newer antibody drug conjugates may help a larger proportion of patients,” indicated Dr. Connolly.
Conclusions
“This was an extremely important study based on the established efficacy benefits of the trastuzumab/pertuzumab combination in HER2-positive breast cancer. We found that select patients with other cancer types with high levels of HER2 amplification benefitted from this approach, which is associated with minimal side effects,” highlighted Dr. Connolly. “As a number of patients in Arm J had shrinkage of their cancers with this dual HER2 blockade, it is clear that select patients with this genomic aberration may benefit from HER2 pathway blockade,” she concluded.
Disclosure: The research in this trial was supported by the National Cancer Institute. For full disclosures of the study authors, visit aacrjournals.org.
