Rezivertinib Improves PFS vs Gefitinib in EGFR-Mutant NSCLC

Results from the phase 3 REZOR trial show a median PFS of 19.3 months with rezivertinib vs 9.6 months with gefitinib in patients with NSCLC.

Rezivertinib (BPI-7711) elicited improved efficacy and progression-free survival (PFS) with no new safety signals compared with gefitinib (Iressa) in patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) harboring an EGFR mutation, according to results from the randomized, double-blind phase 3 REZOR trial (NCT03866499) published in The Lancet Respiratory Medicine.1

At a median follow-up of 24.9 months (95% CI, 24.4-25.8) for the rezivertinib group and 24.4 months (95% CI, 23.1-25.1) in the gefitinib group, the median masked independent central review (MICR)-accessed PFS was 19.3 months (95% CI, 13.8-22.1) vs 9.6 months (95% CI, 8.4-11.3), respectively (HR, 0.48; 95% CI, 0.36-0.63; P <.0001).

Among patients with EGFR exon 19 deletions, the MICR-assessed median PFS was 22.1 months (95% CI, 13.8-not calculated) with rezivertinib vs 9.7 months (95% CI, 8.4-13.8) with gefitinib (HR, 0.38; 95% CI, 0.26-0.57; P <.0001). Of patients with EGFR mutations detected with tissue samples, MICR-assessed median PFS was 20.7 months (95% CI, 13.9-24.9) in the rezivertinib group and 9.7 months (95% CI, 8.3-12.4) in the gefitinib group (HR, 0.47; 95% CI, 0.34-0.66; P <.0001); when EGFR mutations were detected with plasma samples, MICR-assessed median PFS was 16.0 months (95% CI, 9.7-24.9) vs 9.6 months (95% CI, 6.9-11.0), respectively (HR, 0.48; 95% CI, 0.30-0.75; P = .0014).

Among those with EGFR Leu858Arg mutations, the MICR-assessed median PFS was 13.9 months (95% CI, 9.7-17.9) vs 9.6 months (95% CI, 6.9-12.4), respectively (HR, 0.59; 95% CI, 0.40-0.85; P = .0053).

“Rezivertinib (BPI-7711) showed superior overall and subgroup [PFS] efficacy and a manageable safety profile for treatment of patients with locally advanced or metastatic NSCLC with EGFR mutations in the first-line setting when compared with gefitinib,” lead study author Yuanka Shi, MD, a professor in the Department of Medical Oncology at the Cancer Institute and Hospital of Chinese Academy of Medical Sciences, and coauthors wrote in the paper. “In the REZOR study, the consistent clinical benefits for patients shown to have EGFR mutations via tissue or plasma samples at screening also provide a valuable treatment option for patients with unavailable tissue samples.”

A total of 369 patients were randomly assigned, in a 1:1 ratio, to receive either rezivertinib at 180 mg a day plus placebo (n = 184) or gefitinib at 250 mg a day plus placebo (n = 185). Eligible patients were 18 years or older with histologically or cytologically confirmed NSCLC. Additionally, patients needed an ECOG performance status of 0 or 1, at least 1 measurable lesion, and central laboratory confirmation of exon 19 deletion or Leu858Arg mutations.

Those who received previous systemic treatment for their disease, treatment within 14 days before first study drug dose, or had a positive primary Thr790Met mutation were ineligible for exclusion.

The trial’s primary end point was PFS assessed by MICR per RECIST v1.1 criteria. Secondary end points included investigator-assessed PFS, best overall response, objective response rate, disease control rate, duration of response, and time to response.

Median overall survival was not yet mature at the time of analysis, as 157 of 369 (43%) patients were dead; 75 (41%) deaths were in the rezivertinib group, and 82 (44%) were in the gefitinib group (HR, 0.85; 95% CI, 0.62-1.16; P = .29).

For patients with central nervous system (CNS) metastases at baseline, the MICR-assessed median PFS was 16.0 months (95% CI, 12.5-22.2) with rezivertinib vs 9.7 months (95% CI, 8.5-13.8) with gefitinib (HR, 0.52; 95% CI, 0.34-0.80; P = .003); of those without CNS metastases at baseline, MICR-assessed median PFS was 22.0 months (95% CI, 13.8-25.2) vs 9.6 months (95% CI, 7.0-12.4), respectively (HR, 0.46; 95% CI, 0.32-0.65; P <.0001).

The median duration of exposure for rezivertinib was 16.0 months (range, 0.0-29.7) and 11.0 months (range, 0.0-28.9) for gefitinib.

Regarding safety, treatment-emergent adverse events (TEAEs) of any grade and grade 3 or higher occurred in 99% and 45% of the rezivertinib group and 98% and 43% of the gefitinib group. TEAEs led to death, dose adjustment, and treatment termination in 5%, 28%, and 8%, respectively, of the rezivertinib group and 4%, 26%, and 4% of the gefitinib group.

The most common TEAEs of any grade were white blood cell count decreases (41% vs 9%), anemia (36% vs 22%), platelet count decreases (35% vs 6%), and alanine transferase increases (30% vs 39%).

Reference

Shi Y, Guo Y, Li X, et al. 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. Lancet Respir Med. Published online February 3, 2025. doi:10.1016/S2213-2600(24)00417-X