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

"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.