Trastuzumab Deruxtecan Shows Clinically Meaningful Survival Benefits for Patients With Previously Treated HER2-Expressing Tumors

Trastuzumab deruxtecan (Enhertu; AstraZeneca) promotes clinically meaningful progression-free survival (PFS) and overall survival (OS) for patients across multiple human epidermal growth factor receptor 2 (HER2)-expressing advanced solid tumors who received prior treatment, according to primary analysis results from the ongoing DESTINY-PanTumor02 phase 2 trial.

Credit: David A Litman - stock.adobe.com

The trial met secondary endpoints of PFS, OS, and duration of response (DoR), while also meeting the primary endpoint of objective response rate (ORR). No new safety signals were observed either.

“The PFS and OS results for trastuzumab deruxtecan (trastuzumab) alongside the continued robust and durable tumor responses seen with further follow up underscore the potential value of this important medicine for patients with HER2-expressing cancers who currently have no targeted treatment options,” said Cristian Massacesi, chief medical officer and Oncology chief development officer, AstraZeneca, in the press release.

HER2 is a tyrosine kinase receptor growth-promoting protein traditionally involved in cell growth. Some cancers amplify HER2 genes which leads to HER2 protein overexpression, associated with aggressive disease and worse prognosis for many types of cancer, including breast, gastric, lung and colorectal cancers (the current targets of HER2-directed therapies).

DESTINY-PanTumor02 is a phase 2, global, multicenter, multi-cohort, open-label trial assessing the safety and efficacy of trastuzumab in 267 patients with previously treated, locally advanced, unresectable, or metastatic HER2-expressing solid tumors sites from across the globe.

Encouraging phase 2 data illustrate how this growth-promoting protein could be used as a biomarker in biliary tract, bladder, cervical, endometrial, ovarian, and pancreatic cancers. There are still no approved HER2-directed therapies for patients with these HER2-expressing tumors that are refractory to standard of care, and investigators urge further research on treatment for these other HER2-expressing tumor types.

Trastuzumab, co-developed and commercialized by AstraZeneca and Daiichi Sankyo, is currently indicated for adults with unresectable or metastatic HER2-positive breast cancer with disease recurrence following anti-HER2 therapy. It is also indicated for adults with unresectable or metastatic HER2-low breast cancer; unresectable or metastatic non-small cell lung cancer and HER2 mutations following prior systemic therapy; or locally advanced or metastatic HER2-positive gastric cancer following trastuzumab-based therapy.

The primary analysis data bolsters interim analysis results presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting. Investigators will discuss the results of the primary analysis at future meetings.

“These updated results from the DESTINY-PanTumor02 trial are important as we work to reshape the clinical landscape in HER2-expressing advanced cancers,” said Mark Rutstein, global head, Oncology Development, Daiichi Sankyo, in a press release.

“The OS demonstrated by trastuzumab in these patients is a significant step forward in the potential to advance current standards of care and offer new options for patients with HER2-expressing cancers,” Rustein said in the release.

Reference

Enhertu demonstrated clinically meaningful progression-free survival and overall survival across multiple HER2-expressing advanced solid tumours in DESTINY-PanTumor02 Phase II trial. AstraZeneca. July 27, 2023. Accessed July 3, 2023. https://www.astrazeneca.com/media-centre/press-releases/2023/enhertu-demonstrated-clinically-meaningful-progression-free-survival-and-overall-survival-in-destiny-pantumor02-phase-ii-trial.html