Amol Akhade/hiranandanihospital.org
Aug 29, 2025, 19:35
Amol Akhade: HARMONi-A and the Curious Case of OS
Amol Akhade, Senior Consultant at Fortis Hospitals Mumbai, shared a post on X:
“HARMONi-A and the Curious Case of OS: From ‘Negative Drift’ to a Positive Surprise
One of the most anticipated stories at WCLC25 will be the HARMONi-A trial of ivonescimab (PD-1/VEGF bispecific) in EGFR-mutated, TKI-resistant NSCLC.
Why? Because the overall survival (OS) curve has done something unusual.
What once looked negative has now turned positive.
The OS Journey
1. March 10, 2023 – First Interim (~21% OS events, ASCO 2024/JAMA)
- Median follow-up: ~7.9 months
- OS HR ≈ 0.72 (~28% risk reduction)
- Immature but encouraging signal
2. May 30, 2025 – Multiregional Interim (~52% maturity)
- OS HR ≈ 0.79–0.80 (~20% reduction)
- 95% CI: 0.62–1.01, p ≈ 0.057
- Analysts called it ‘drift,’ unlikely to succeed
3. August 26, 2025 – Final Analysis
- OS was declared statistically significant and clinically meaningful
- A true positive surprise if u look at earlier results
What could explain the turnaround?
- Global vs China data: did rest-of-world results balance weaker China outcomes? (30 % ~)
- Late separation: IO/VEGF combos often show delayed survival benefit with a “tail effect.”
- Post-progression therapy: differences in salvage treatment may unmask survival benefit only with longer follow-up.
What makes it more interesting is that this trial is not powered for OS. So the p-value will be a Nominal p-value.
Let’s wait for WCLC25 to see the full curves and subgroup breakdowns.”
More posts featuring Amol Akhade.
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Challenging the Status Quo in Colorectal Cancer 2024
December 6-8, 2024
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ESMO 2024 Congress
September 13-17, 2024
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ASCO Annual Meeting
May 30 - June 4, 2024
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Yvonne Award 2024
May 31, 2024
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OncoThon 2024, Online
Feb. 15, 2024
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Global Summit on War & Cancer 2023, Online
Dec. 14-16, 2023
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