Cardio-oncology & otherMeta-analysis
Cardiovascular adverse events associated with epidermal growth factor receptor tyrosine kinase inhibitors in epidermal growth factor receptor (EGFR)- mutated non-small cell lung cancer: systematic review and network meta-analysis
- Systematic review and network meta-analysis of randomised trials
- random effects
- frequentist
Authors' conclusion
In patients with EGFR-mutated NSCLC, first and third generation EGFR tyrosine kinase inhibitors, as well as combination therapies with antiangiogenesis, were associated with increased risks of cardiovascular adverse events. Risks were significantly higher with third generation compared with first generation inhibitors.
Study context
- Population
- Patients with EGFR-mutated non-small cell lung cancer
- Participants
- 29,813 patients · 89 RCTs
- Comparison
- EGFR tyrosine kinase inhibitors vs placebo or other treatments
- Outcome
- CV adverse events
- Follow-up
- Mean 2.18 years
Pooled result
As reported in the abstract
Cardiac adverse events
Each group vs placeboOdds ratio (95% CI)
First generation
1.51(1.01–2.26)
Third generation
2.18(1.46–3.27)
Further pooled results
| Outcome | First generation | Third generation | Placebo | OR (95% CI) | |
|---|---|---|---|---|---|
| Cardiac adverse events, individual third generation inhibitors vs placebo — Osimertinib vs Placebo · high certainty | 2.53 (1.53–4.19) | ||||
| Cardiac adverse events, individual third generation inhibitors vs placebo — Lazertinib vs Placebo · moderate certainty | 2.84 (1.17–6.91) | ||||
| Arrhythmias vs placebo — Third generation vs Placebo · high certainty | Not reported in the abstract | pooled incidence 7.3% | Not reported in the abstract | 3.26 (1.83–5.81) | |
| Arrhythmias vs placebo — Osimertinib vs Placebo · high certainty | 3.35 (1.75–6.40) | ||||
| 0.10.31310Odds ratio (log scale) |
- Cardiac adverse events, individual third generation inhibitors vs placebo: Osimertinib pooled incidence 8.9%
- Cardiac adverse events, individual third generation inhibitors vs placebo: Lazertinib pooled incidence 2.7%
- Arrhythmias vs placebo: Osimertinib pooled incidence 6.2%
Combination therapies and other agents
- Antiangiogenesis with erlotinib or gefitinib associated with vascular adverse events (high certainty)
- Antiangiogenesis with osimertinib associated with CV adverse events (moderate to high certainty)
- Almonertinib associated with vascular toxicity
Any grade and grade ≥3 CV adverse events, third vs first generation (pairwise meta-analysis)
- Higher risks with third generation than first generation inhibitors
Original publication
Cardiovascular adverse events associated with epidermal growth factor receptor tyrosine kinase inhibitors in EGFR- mutated non-small cell lung cancer: systematic review and network meta-analysis. BMJ. Published 2 September 2025. doi:10.1136/bmj-2024-082834
Summarised from the published abstract; every number is checked against it