3D model of HER2 complexed with Herceptin (trastuzumab)
Credit: Hao Jiang/Getty Images

New data from the National Cancer Institute’s Molecular Analysis for Therapy Choice (NCI-MATCH) precision medicine clinical trial has shown in a Phase II study that the trastuzumab-pertuzumab combination therapy, already approved for the treatment of HER2-positive breast cancer, shrunk the tumors of several other cancer types. The findings warrant additional research to determine if the combo therapy can be used to treat other cancers with high levels of the HER2 gene.

“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,” said lead investigator Roisin M. Connolly, MD, of University College Cork in Ireland, and the ECOG-ACRIN Cancer Research Group (ECOG-ACRIN).

The findings, published today in the journal Clinical Cancer Research, were from NCI-MATCH Arm J, a single-arm Phase II trial to study the efficacy of trastuzumab-pertuzumab with metastatic HER2-amplified cancer other than breast cancer. The study excluded patients with gastric cancer or gastroesophageal junction adenocarcinoma, as these have approved targeted treatments.

For this study arm, the researchers recruited patients with high levels of HER2 amplification, defined as a number of seven or more. It enrolled 35 patients and the primary analysis included 25 based on central evaluations of HER2 amplification. Median age was 65, 56% of those enrolled were female and more than half had received at least three prior therapies. Eleven patients in the study had gynecologic cancer, eleven with gastrointestinal cancer, two with urinary bladder cancer, and one with head and neck cancer.

Overall response rate of patients evaluated was 12%, or three of 25 patients, with all three showing partial response the drug combination. Each of the three had a different cancer: adenocarcinoma of the rectum, cholangiocarcinoma, and transitional cell carcinoma of the bladder. Partial response was observed in one other patients with urothelial cancer and an unconfirmed HER2 copy number. Stable disease was observed in nine patients with cholangiocarcinoma, gynecologic, and colorectal cancers.

Connolly noted these findings indicate that select patients could stand to benefit from trastuzumab-pertuzumab treatments, but the authors also said their study came up just short of the primary endpoint of ORR greater than 16%, or four of 25 patients.

“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, such as combinations with chemotherapy, or newer antibody drug conjugates, may help a larger proportion of patients,” Connolly added.

NCI-MATCH is a broad precision medicine basket trial that has enrolled patients in 38 different Phase II trial treatment arms based on different genomic alteration found in tumor tissue. Many of the treatment arms are completed and have published results.

While NCI sponsored this arm, the combination therapy trastuzumab-pertuzumab was supplied by Genentech via a Clinical Trial Participation Agreement with NCI.

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