Dr Lee on the Significance of the Tumor-Agnostic Approval of T-DXd for HER2+ Urothelial Cancer

John K. Lee, MD, PhD, assistant professor, medicine, UCSF; director, Bladder Cancer Program, UCSF Helen Diller Family Comprehensive Cancer Center, discusses the significance of the tumor-agnostic approval of fam-trastuzumab deruextecan-nxki (Enhertu; T-DXd) in patients with HER2-positive urothelial cancer.

The FDA granted accelerated approval to T-DXd for the treatment of adult patients with unresectable or metastatic HER2-positive (immunohistochemistry [IHC] 3+) solid tumors who have received prior systemic therapy and have no satisfactory alternative treatment options in April, 2024, Lee begins. The regulatory decision was supported by data from the phase 2 DESTINY-PanTumor02 (NCT04482309), DESTINY-Lung01 (NCT03505710), and DESTINY-CRC02 (NCT04744831) trials, he reports. Across all studies, T-DXd was shown to have significant efficacy across a range of HER2-positive solid tumors, Lee says.

The DESTINY-PanTumor02 study evaluated the efficacy of T-DXd at a dose of 5.4 mg/kg every 3 weeks in patients with locally advanced or metastatic HER2-positive disease who had undergone at least one prior line of systemic therapy, Lee continues. This trial enrolled eligable patients across 7 different cohorts based on tumor type, comprising endometrial, cervical, ovarian, bladder, biliary tract, and pancreatic cancers, as well as other advanced solid tumors, he details.

The trial's findings revealed that patients with HER2-positive IHC 3+ tumors achieved notably higher response rates compared with those with HER2-positive IHC 2+ tumors, Lee reports. Importantly, T-DXd demonstrated significant progression-free survival benefits for patients in the IHC 3+ group, further solidifying its role as a promising therapeutic option. These results were consistent across multiple tumor types, establishing T-DXd as an effective treatment in a tumor-agnostic fashion for patients with HER2-positive cancers, Lee says. This approval is not only significant for patients with bladder cancer, but is impactful across the board for patients who have no other available treatment options, he concludes.