ASCO Perspective

“This study provides data for an unmet need for patients who have exhausted standard therapeutic options with tumors that overexpress HER2 for which no drug is yet approved. While additional follow-up is needed, there is robust activity across multiple HER2 expressing tumors with over 50% response rate in those with the highest levels of HER2 expression coupled with an encouraging safety profile. Trastuzumab deruxtecan could provide a new treatment option for these patients,” said Bradley Alexander McGregor, MD, ASCO Expert.

Trastuzumab deruxtecan is an effective treatment option for people with difficult-to-treat HER2-expressing solid tumors, according to the findings of an international study.

Study at a Glance

Key Findings

In the phase II open-label DESTINY-PanTumor02 study, patients with HER2-expressing (immunohistochemistry [IHC] 3+ or IHC 2+) locally advanced or metastatic disease that had worsened after at least one systemic treatment or that had no treatment options were treated with at least one dose of trastuzumab deruxtecan. At the median follow-up of 9.7 months, the treatment resulted in an ORR of 37.1% (ORR is a measure of the number of partial and complete responses to a treatment). The amount of time that tumors continued to respond to treatment – measured by the mDOR – was 11.8 months. In patients with higher levels of HER2 expression (i.e., IHC 3+), trastuzumab deruxtecan was even more effective, resulting in an ORR of 61.3% and an mDOR of 22.1 months. Across different disease sites, trastuzumab deruxtecan resulted in the following ORRs:

• Endometrial cancer: 57.5% for all patients, 84.6% for IHC 3+, and 47.1% for IHC 2+
• Cervical cancer: 50% for all patients, 75% for IHC 3+, 40% for IHC 2+
• Ovarian cancer: 45% for all patients, 63.6% for IHC 3+, 36.8% for IHC 2+
• Urothelial cancer: 39% for all patients, 56.3% for IHC 3+, 35% for IHC 2+
• Biliary tract cancer: 22% for all patients, 56.3% for IHC 3+, 0% for IHC 2+
• Pancreatic cancer: 4% for all patients, 0% for IHC 3+, 5.3% for IHC 2+.

The study participants were mostly able to tolerate treatment with trastuzumab deruxtecan, however, 11.6% of participants stopped treatment due to adverse events. The most common treatment-related side effects were nausea, fatigue, and low levels of blood cells (cytopenia).

“HER2 is present in many cancer types, such as breast, gastric, lung, gynecologic, and urothelial cancers, and patients with HER2-expressing, hard-to-treat cancers need new treatment options,” said Funda Meric-Bernstam, MD, chair of the Department of Investigational Cancer Therapeutics at the University of Texas MD Anderson Cancer Center and lead author of the study. “These results advance our clinical understanding of HER2 expression, reaffirm HER2 as an actionable biomarker across a broad range of tumor types, and show that trastuzumab deruxtecan could potentially provide a new treatment option for patients with advanced disease across these tumors, especially in patients with HER2 IHC 3+ or 2+ expression.”

About the Study

Patients with HER2-expressing biliary tract, bladder, cervical, endometrial, ovarian, pancreatic, or other tumors (excluding breast, gastric, colorectal and non-small cell lung cancers) were enrolled in the study. There were 267 patients, including 75 patients with IHC 3+ expression and 125 with IHC 2+ expression. IHC is the amount of HER2 receptor protein present in cells.

Although HER2 is expressed across a variety of tumor types, there are currently no approved HER2-targeted therapies for many types of cancer, especially those that are hard to treat. Trastuzumab deruxtecan is an antibody drug conjugate targeting HER2 that is currently approved by the U.S. Food and Drug Administration for HER2-expressing breast cancer, HER2+ gastric cancer, and lung cancers with HER2-mutations. This study is the first global study of tumor-agnostic applications for trastuzumab deruxtecan across a broad range of HER2-expressing solid tumors.

Next Steps

The researchers are currently collecting additional survival outcomes in the DESTINY-PanTumor02 study.