Amol Akhade, Senior Consultant at Fortis Hospitals Mumbai, shared a post on LinkedIn:
“HERIZON-GEA-01 (LBA285): progress, but with important caveats.
HER2-positive metastatic gastric/GEJ cancer remains a space where incremental gains have often been mistaken for breakthroughs.
HERIZON-GEA-01 is an important trial, but it deserves careful interpretation beyond headline numbers.
This global phase III study enrolled 914 previously untreated HER2+ metastatic gastric/GEJ cancer patients, randomized 1:1:1 to:
- trastuzumab + chemotherapy (control),
- zanidatamab + chemotherapy,
- zanidatamab + tislelizumab + chemotherapy.
Importantly, the trial was PD-L1 agnostic.
Efficacy signals are clear on PFS.
Median PFS improved from 8.1 months with trastuzumab + CT to 12.4 months with zanidatamab + CT (HR 0.65) and 12.4 months with the triplet (HR 0.63). This suggests that stronger HER2 blockade upfront matters, independent of immunotherapy.
Overall survival, however, tells a more nuanced story.
Median OS was 19.2 months in the control arm, 24.4 months with zanidatamab + CT (HR 0.80, interim, not statistically significant), and 26.4 months with zanidatamab + tislelizumab + CT (HR 0.72, P=0.004).
In other words, a statistically significant OS benefit is observed only with the triplet, not with zanidatamab doublet alone.
Toxicity is not trivial.
Grade ≥3 adverse events reached ~72% with the triplet regimen, with higher treatment discontinuation rates compared with the control arm. This matters greatly when considering real-world patients, especially outside highly selected trial populations.
Key questions that remain unanswered:
Is the OS benefit driven by better HER2 targeting, or simply by adding immunotherapy?
What is the magnitude of benefit specifically in PD-L1–negative patients?
How should we interpret results when the control arm does not include pembrolizumab, given KEYNOTE-811?
Does therapy intensification justify higher toxicity and cost across all settings?
Check out comparisons between keynote 811 and Herzon GEA 01
more details after full data is presented.”
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