At the ESMO GI Cancers Congress 2026, Kohei Shitara presented health-related quality of life results from the phase 3 HERIZON-GEA-01 trial in patients with first-line HER2-positive advanced or metastatic gastroesophageal adenocarcinoma.
The presentation, titled “Health-related quality of life (HRQoL) with zanidatamab (zani) + chemotherapy (CT) ± tislelizumab (TIS) for first-line (1L) HER2-positive (HER2+) advanced/metastatic gastroesophageal adenocarcinoma (mGEA): Results from HERIZON-GEA-01,” was presented as abstract 494O.
Background
In the first interim analysis of HERIZON-GEA-01, zanidatamab plus chemotherapy with or without tislelizumab significantly improved progression-free survival compared with trastuzumab plus chemotherapy. The zanidatamab plus tislelizumab plus chemotherapy arm also showed a significant overall survival benefit versus trastuzumab plus chemotherapy.
Median PFS by blinded independent central review was 12.4 months in both zanidatamab-containing arms versus 8.1 months with trastuzumab plus chemotherapy. Median OS was 26.4 months with zanidatamab plus tislelizumab plus chemotherapy and 24.4 months with zanidatamab plus chemotherapy, versus 19.2 months with trastuzumab plus chemotherapy. The OS benefit was statistically significant for zanidatamab plus tislelizumab plus chemotherapy, while zanidatamab plus chemotherapy showed a numerical OS improvement.
Methods
HERIZON-GEA-01 is a phase 3 study evaluating zanidatamab-based first-line treatment in HER2-positive advanced or metastatic gastroesophageal adenocarcinoma. The clinical trial identification number is NCT05152147.
Patients were randomized 1:1:1 to receive:
- Zanidatamab plus tislelizumab plus chemotherapy
- Zanidatamab plus chemotherapy
- Trastuzumab plus chemotherapy
Treatment was given in 21-day cycles.
Health-related quality of life was a prespecified secondary endpoint and was assessed using the EORTC QLQ-C30 questionnaire. Assessments were performed at baseline, day 1 of each cycle through cycle 12, every other cycle thereafter, and at end of treatment.
Read more about HERIZON-GEA-01 updates on OncoDaily.
Key Findings
Completion rates for the EORTC QLQ-C30 questionnaire were high across the study. Completion rates were greater than 95% through cycle 34 day 1 in each treatment arm. Among patients who discontinued treatment, end-of-treatment completion rates were greater than 60% across arms.
Changes from baseline in most domains and global health scores were numerically similar across the three treatment arms. Mean baseline physical functioning scores were similar across treatment arms, ranging from 81.5 to 83.5.
At cycle 2 day 1, reductions in physical functioning were slightly larger with zanidatamab plus chemotherapy and zanidatamab plus tislelizumab plus chemotherapy compared with trastuzumab plus chemotherapy. These differences were small and remained small during the rest of the on-treatment period.
Between cycle 2 day 1 and cycle 8 day 1, the proportion of patients who maintained or improved physical functioning from baseline remained high across all treatment arms.
Global Health Status/QoL findings were consistent with the physical functioning results. Across treatment arms, there were no substantive changes in Global Health Status/QoL from baseline over time.
Diarrhea was the most common treatment-related adverse event in all treatment arms and was reported more often in the zanidatamab-containing arms. At cycle 8 day 1, diarrhea also showed the greatest worsening from baseline among EORTC QLQ-C30 symptom scales.
You can also read about Zanidatamab (Ziihera) Updates 2025 on OncoDaily.
Conclusions
In HERIZON-GEA-01, zanidatamab-containing regimens improved progression-free survival, and zanidatamab plus tislelizumab plus chemotherapy also showed a statistically significant overall survival benefit, while maintaining physical functioning and without detriment to overall health-related quality of life.
These HRQoL findings support zanidatamab plus chemotherapy with or without tislelizumab as a first-line treatment approach for patients with HER2-positive advanced or metastatic gastroesophageal adenocarcinoma.
Expert Highlights
Arndt Vogel shared on X:
“HRQoL with zani + CTx ± tislelizumab for 1L HER2-positive mGEA: Results from HERIZON-GEA-01
ESMOGI26
Improved outcome without significant impact on QoLPts reported diarrhoea consistent with safety profile
Supports Zani as new SOC”
Erman Akkus also shared on X:
“HERIZON-GEA-01 HRQoL results
proffered paper ESMOGI26No deteriotion”
More details are available in the official ESMO Gastrointestinal Cancers Congress 2026 programme.