Rezivertinib bests gefitinib in first-line treatment of advanced EGFR-mutant NSCLC

In the first-line treatment of patients with EGFR-mutated locally advanced or metastatic non–small-cell lung cancer (NSCLC), the novel third-generation EGFR tyrosine kinase inhibitor rezivertinib yields superior overall efficacy and progression-free survival (PFS) when compared with gefitinib, with no new safety signals, according to the phase III REZOR trial.

REZOR included 369 NSCLC patients with EGFR exon 19 deletion or exon 21 Leu858Arg mutation. These patients were randomly assigned to receive either rezivertinib at 180 mg per day plus placebo (n=184) or gefitinib at 250 mg per day plus placebo (n=185). Treatment was given until unacceptable toxicity occurred, disease progression, or other treatment discontinuation criteria were met. Each cycle lasted for 21 days.

PFS, the primary endpoint, was assessed by masked independent central review (MICR) in the intention-to-treat population.

Median MICR-assessed PFS was significantly longer with rezivertinib than with gefitinib (19.3 vs 9.6 months; hazard ratio [HR], 0.48, 95 percent confidence interval [CI], 0.36–0.63; p<0.0001). Results were consistent in the prespecified subgroup efficacy analysis.

The median duration of exposure was 16.0 months (95 percent CI, 0.0–29.7) in the rezivertinib arm and 11.0 months (95 percent CI, 0.0–28.9) in the gefitinib arm. Grade 3 or higher treatment-emergent adverse events did not differ between rezivertinib and gefitinib (45 percent vs 43 percent, respectively), nor did treatment-related adverse events (TRAEs) (23 percent vs 23 percent). One rezivertinib-treated patient died from a TRAE, particularly pneumonia and interstitial lung disease.