Nicholas Hornstein, Assistant Professor at Northwell Health, shared on LinkedIn:
Zanidatamab is now FDA approved in 1L HER2+ metastatic/unresectable gastric, GEJ, and esophageal adenocarcinoma.
Back at GI26, after HERIZON-GEA-01, I wrote:
We have a new first line.
Now its official.
For context:
ToGA established trastuzumab + chemo in 2010. KEYNOTE-811 added pembrolizumab. But trastuzumab stayed the HER2 backbone for ~15 years.
HERIZON changes that.
Zanidatamab + tislelizumab + chemo vs trastuzumab + chemo:
- PFS 12.4 vs 8.1 mo
- HR 0.63
- OS 26.4 vs 19.2 mo
- HR 0.72
That is a meaningful step forward (with one caveat). This was not compared against trastuzumab + pembrolizumab + chemo, so we do not have a direct KEYNOTE-811 head-to-head.
Practically though,
- IHC 3+ or IHC 2+/ISH+, IO eligible: zani + PD1+ chemo is now my 1L option
- IHC 3+, no IO: zani + chemo is also FDA approved (although the PDL1 null subgroup is its own complicated + somewhat confusing discussion)
And please, for the love of all things GI oncology:
WATCH FOR DIARRHEA. ESPECIALLY THE FIRST 2 CYCLES.
- Any-grade diarrhea was 83%.
- Grade ≥3: ~25%.
Most first episodes happened early. The study mandated loperamide prophylaxis in cycle 1.
PLEASE counsel aggressively, have loperamide in hand before treatment starts, and watch hydration/electrolytes closely.
With that said, excited that we finally have a new HER2 backbone in gastroesophageal cancer.”
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