According to the findings of the international phase II DESTINY-PanTumor02 study presented by Funda Meric-Bernstam, MD, and colleagues at the 2023 ASCO Annual Meeting, fam-trastuzumab deruxtecan-nxki (T-DXd) is an effective treatment option for people with difficult-to-treat, HER2-expressing solid tumors (Abstract LBA3000).
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. T-DXd 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-positive gastric cancer, and lung cancers with HER2 mutations.
Funda Meric-Bernstam, MD
About DESTINY-PanTumor02
DESTINY-PanTumor02 is the first global study of tumor-agnostic applications for T-DXd across a broad range of HER2-expressing solid tumors. 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 enrolled in the trial, including 75 patients with immunohistochemistry (IHC) 3+ expression and 125 with IHC 2+ expression. Patients had locally advanced or metastatic disease that had worsened after at least one systemic treatment or that had no treatment options. They were treated with at least one dose of T-DXd.
Key Findings
At a median follow-up of 9.7 months, T-DXd resulted in an objective response rate of 37.1%. The median duration of response was 11.8 months. In patients with higher levels of HER2 expression (ie, IHC 3+), T-DXd was even more effective, resulting in an objective response rate of 61.3% and a median duration of response of 22.1 months. Across different disease sites, T-DXd resulted in the following objective response rates:
- 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+ and 40% for IHC 2+)
- Ovarian cancer: 45% for all patients (63.6% for IHC 3+ and 36.8% for IHC 2+)
- Urothelial cancer: 39% for all patients (56.3% for IHC 3+ and 35% for IHC 2+)
- Biliary tract cancer: 22% for all patients (56.3% for IHC 3+ and 0% for IHC 2+)
- Pancreatic cancer: 4% for all patients (0% for IHC 3+ and 5.3% for IHC 2+).
The study participants were mostly able to tolerate treatment with T-DXd; however, 11.6% of participants stopped treatment due to adverse events. The most common treatment-related side effects were nausea, fatigue, and 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 lead study author Dr. Meric-Bernstam, Chair of the Department of Investigational Cancer Therapeutics at the University of The University of Texas MD Anderson Cancer Center. “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 T-DXd 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.”
Next Steps
The researchers are currently collecting additional survival outcomes in the DESTINY-PanTumor02 study.
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 [an] over 50% response rate in those with the highest levels of HER2 expression coupled with an encouraging safety profile. [T-DXd] could provide a new treatment option for these patients,” said ASCO expert Bradley Alexander McGregor, MD.
Disclosure: This study was sponsored and designed by AstraZeneca in collaboration with Daiichi Sankyo. For full disclosures of the study authors, visit coi.asco.org.
