A Breast Cancer Treatment Shows Clinical Activity in Multiple Cancer Types

A new study suggests that a HER2-targeted therapy approved for breast cancer may be effective for several other cancers.

Human epidermal growth factor receptor 2 (HER2) is a protein that can promote cancer progression when mutated or when found at high levels on the surface of cells. High levels of HER2 have been observed in many different cancer types, including breast, gastric, lung, and colorectal cancers. 

Several therapeutics that target HER2-positive cancer cells are approved in the United States for the treatment of breast cancer, and one such therapy is approved for gastric cancer.

“Therapies that target HER2-expressing cells have proven successful for patients with breast and gastric cancers; however, there are no approved HER2-targeted therapies available for patients with other malignancies,” said Bob Li, MD, medical oncologist at Memorial Sloan Kettering Cancer Center. “Conventional therapies for these other cancers tend to have limited efficacy and considerable side effects. Additional treatment options are urgently needed for these patients.”

“Therapies that target HER2 can be selectively directed to cancer cells, which could improve efficacy and help reduce toxicities caused by off-target effects on normal cells,” said Junji Tsurutani, MD, PhD, medical oncologist at the Advanced Cancer Translational Research Institute at Showa University in Tokyo. 

In a phase I study published in Cancer Discovery, a journal of the American Association for Cancer Research, Tsurutani, Li, and colleagues tested the safety and clinical activity of a HER2-targeted drug called fam-trastuzumab deruxtecan-nxki (T-DXd) in patients with several different advanced solid tumors. 

T-DXd was approved by the U.S. Food and Drug Administration in December 2019 for the treatment of some patients with HER2-positive breast cancer.

The latest publication reports data from 60 patients with non-breast/non-gastric solid tumors, including colorectal, non-small cell lung, salivary gland, esophageal, endometrial, and pancreatic cancers, among other types. 

Approximately 28 percent of patients treated with T-DXd responded to the treatment, with a median overall survival of approximately 23 months. The median progression-free survival, which is the amount of time that passes before disease progression, was approximately seven months. The objective response rate was greatest for patients with non-small cell lung cancer, with 55.6 percent of these patients having a confirmed response.

The frequency of adverse events was similar across the different tumor types. Overall, 30.5 percent of patients experienced serious adverse events, and five patients had drug-related interstitial lung disease, a serious and potentially fatal complication. Five patients experienced an adverse event with a fatal outcome, of which two were reported to be treatment-related. One of the treatment-related deaths was due to drug-related interstitial lung disease. 

“The safety profile of T-DXd is consistent with the previously reported breast and gastric cancer cohorts from this phase I study,” said Li. “Interstitial lung disease is an important identified adverse event that may be serious – even fatal – and thus requires monitoring and prompt intervention. Further research is required to minimize and manage this risk.”

“T-DXd demonstrated promising antitumor activity in a heterogeneous patient population,” said Tsurutani. “These results indicate that T-DXd should be explored in larger studies as a treatment option for patients with HER2-overexpressing or HER2-mutated solid tumors.”

Li noted, “We are very excited by the results of this preliminary study. T-DXd shows early promise for transforming the standard of care for patients with HER2-overexpressing or HER2-mutated cancers and we look forward to continuing this important research in future clinical trials.”

Another study published by Li and colleagues in Cancer Discovery suggested that T-DXd could also be explored as a treatment for patients who relapse after receiving other HER2-targeted therapies. In this study, T-DXd led to a partial response in a patient with lung cancer who had relapsed after treatment with another HER2-targeted drug called ado-trastuzumab emtansine (T-DM1).