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Rezivertinib versus gefitinib as first-line therapy for patients with EGFR-mutated locally advanced or metastatic non-small-cell lung cancer (REZOR): a multicentre, double-blind, randomised, phase 3 study.

The Lancet. Respiratory medicine2025-02-07PubMed
Total: 84.0Innovation: 7Impact: 9Rigor: 9Citation: 9

Summary

In 369 EGFR-mutated NSCLC patients, rezivertinib nearly doubled median progression-free survival versus gefitinib (19.3 vs 9.6 months; HR 0.48) with similar rates of grade ≥3 treatment-related adverse events. One treatment-related death (pneumonia/interstitial lung disease) occurred with rezivertinib.

Key Findings

  • Median PFS 19.3 months with rezivertinib vs 9.6 months with gefitinib (HR 0.48, p<0.0001).
  • Grade ≥3 treatment-emergent and treatment-related adverse events were similar between arms (23% TRAEs in each arm).
  • One treatment-related death (pneumonia/interstitial lung disease) occurred in the rezivertinib arm.

Clinical Implications

Rezivertinib is a strong first-line option for EGFR exon19del/L858R NSCLC. Clinicians should weigh PFS benefit against potential ILD risk, monitor closely, and await OS/CNS outcomes and comparative data versus osimertinib.

Why It Matters

This high-quality phase 3 RCT provides compelling first-line evidence for a next-generation EGFR TKI that significantly prolongs PFS compared with gefitinib. It is likely to influence treatment algorithms in EGFR-mutated NSCLC.

Limitations

  • Population entirely in China; generalizability outside East Asia uncertain.
  • Overall survival and CNS efficacy not yet mature; no head-to-head comparison with osimertinib.

Future Directions

Head-to-head comparisons with third-generation TKIs (e.g., osimertinib), evaluation of CNS control, resistance mechanisms, and sequencing strategies; broader multiethnic confirmatory trials.

Study Information

Study Type
RCT
Research Domain
Treatment
Evidence Level
I - Randomized, double-blind phase 3 trial with independent central review.
Study Design
OTHER