HARMONi randomised 438 patients with advanced EGFR-mutated non-small-cell lung cancer progressing on EGFR tyrosine kinase inhibitor therapy to ivonescimab plus chemotherapy or placebo plus chemotherapy. Seventy per cent were Asian, 59% female.
Median progression-free survival was 6.8 months against 4.4, a hazard ratio of 0.52 with an interval from 0.41 to 0.66. Overall survival at a median 29.7 months of follow-up was 16.8 against 14.0 months, a hazard ratio of 0.79 with an interval from 0.62 to 1.01 — a promising direction that does not yet exclude no effect.
The toxicity is the trade. Serious treatment-related adverse events occurred in 61 patients (28%) with ivonescimab and 33 (15%) without. Grade 3-4 thrombocytopenia doubled, 12% against 6%. Treatment-related deaths were four against five, so the fatal events did not differ, but the burden of serious events did.
This is the recurring shape of post-TKI progression: a real and substantial delay in progression, an overall survival signal that has not yet crossed the line, and a near-doubling of serious adverse events. Whether that trade is worth making depends on what the patient is optimising for, and that is a conversation rather than a guideline.
- Population is post-TKI progression specifically, not first-line EGFR-mutant disease
- Progression-free survival gain is 2.4 months in absolute terms
- Overall survival interval reaches 1.01 — not significant on current follow-up
- Serious treatment-related adverse events nearly doubled, 28% against 15%
- 70% Asian cohort; generalisability outside that population is untested here
The statistics, in plain English
The progression-free survival hazard ratio of 0.52, interval 0.41 to 0.66, is precise and clearly real. The overall survival hazard ratio of 0.79, interval 0.62 to 1.01, is the more consequential and the less certain: it includes no benefit, just. Progression-free survival is a surrogate — it measures when a scan changes, not when a patient does — so the survival result is the one to wait for.
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