Elena Elimova, MD, is an Associate Professor, Department of Medicine, University of Toronto, Staff Medical Oncologist, Princess Margaret Hospital.

Elimova

"The OS results were finally mature, and we found that the median OS in both the all-treated population, which did include some HER2-negative patients, and in the HER2-positive population, was 36.5 months."

Elena Elimova, MD, a gastrointestinal medical oncologist at Princess Margaret Cancer Centre, discussed long-term efficacy outcomes and translational findings from a phase 2 trial (NCT03929666) evaluating first-line zanidatamab (Ziihera) in combination with chemotherapy for patients with HER2-positive advanced or metastatic gastroesophageal adenocarcinoma.

The phase 2 trial enrolled patients with centrally confirmed HER2-positive tumors, with a small subset of HER2-negative patients included in the all-treated population. At a median follow-up of 48 months (range, 29-59), the median overall survival (OS) was 36.5 months (95% CI, 23.6-not evaluable) across both the HER2-positive and all-treated cohorts.

In the overall population, the confirmed objective response rate (ORR) was 76% (95% CI, 60%-88%), with a median progression-free survival (PFS) of 12.5 months (95% CI, 8.2-21.8) and a median duration of response (DOR) of 18.7 months (95% CI, 10.4-44.1). In the HER2-positive population, these respective results were 84% (95% CI, 68%-94%), 15.2 months (95% CI, 9.5-33.4), and 20.4 months (95% CI, 8.3-44.1).

Elimova noted that translational data showed strong concordance between circulating tumor DNA (ctDNA)–based next-generation sequencing (NGS) and tissue-based fluorescence in situ hybridization (FISH) testing for HER2 amplification. Early declines in total ctDNA levels during treatment suggested that ctDNA dynamics may serve as a noninvasive biomarker for therapeutic response.

These updated results underscore the clinical potential of zanidatamab-based strategies in HER2-positive gastroesophageal adenocarcinoma, Elimova added. The survival outcomes and tolerability profile further support the ongoing investigation in the global, randomized phase 3 HERIZON-GEA-01 trial (NCT05152147), which is assessing zanidatamab with chemotherapy with or without immunotherapy. Further research will help define the role of this regimen in biomarker-selected populations and clarify the utility of ctDNA for response monitoring, Elimova concluded.

Videos

Elena Elimova, MD, discusses the efficacy of zanidatamab with chemotherapy in HER2-positive advanced gastroesophageal adenocarcinoma.

Elena Elimova, MD

Articles

Dr Elimova on the Efficacy of Zanidatamab With Chemotherapy in HER2+ Advanced/Metastatic Gastroesophageal Adenocarcinoma