A Phase III clinical trial has demonstrated that rezivertinib (BPI-7711) significantly outperforms gefitinib (Iressa) as a first-line treatment for patients with EGFR-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), potentially establishing a new standard of care for this patient population.
The multicenter, double-blind, randomized REZOR study, conducted across 50 hospitals in China, enrolled 369 patients with histologically or cytologically confirmed NSCLC harboring EGFR exon 19 deletion or exon 21 Leu858Arg mutations. Participants were randomized 1:1 to receive either rezivertinib (180 mg/day) or gefitinib (250 mg/day) until disease progression, unacceptable toxicity, or other discontinuation criteria were met.
Superior Progression-Free Survival
At a median follow-up of approximately 24 months, rezivertinib demonstrated a striking improvement in the primary endpoint of progression-free survival (PFS). The median PFS assessed by masked independent central review (MICR) was 19.3 months (95% CI: 13.8–22.1) in the rezivertinib group compared to just 9.6 months (95% CI: 8.4–11.3) in the gefitinib group, representing a 52% reduction in the risk of disease progression or death (HR: 0.48; 95% CI: 0.36–0.63; P<0.0001).
The benefit was consistent across key subgroups. Patients with EGFR exon 19 deletions showed particularly impressive results with rezivertinib, achieving a median PFS of 22.1 months versus 9.7 months with gefitinib (HR: 0.38; P<0.0001). Those with EGFR Leu858Arg mutations also benefited, with a median PFS of 13.9 months versus 9.6 months (HR: 0.59; P=0.0053).
Efficacy in CNS Metastases
Notably, rezivertinib demonstrated significant efficacy in patients with central nervous system (CNS) metastases at baseline, a common and challenging complication in NSCLC. In this subgroup, the median PFS was 16.0 months with rezivertinib versus 9.7 months with gefitinib (HR: 0.52; P=0.003).
"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," noted 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.
Comparable Safety Profile
The safety profiles of both treatments were generally comparable. Grade 3 or higher treatment-emergent adverse events (TEAEs) occurred in 45% of rezivertinib-treated patients and 43% of gefitinib-treated patients. Treatment-related adverse events of grade 3 or higher were identical between groups at 23%.
The most common TEAEs with rezivertinib included white blood cell count decreases (41% vs 9% with gefitinib), anemia (36% vs 22%), platelet count decreases (35% vs 6%), and alanine transferase increases (30% vs 39%). One patient in the rezivertinib group died from a treatment-related adverse event (pneumonia and interstitial lung disease).
Treatment Duration and Exposure
The median duration of exposure was longer in the rezivertinib group at 16.0 months (range: 0.0-29.7) compared to 11.0 months (range: 0.0-28.9) in the gefitinib group, reflecting the extended progression-free interval.
TEAEs led to dose adjustments in 28% of rezivertinib patients versus 26% of gefitinib patients, while treatment termination occurred in 8% versus 4%, respectively.
Clinical Implications
These findings position rezivertinib as a potentially superior first-line treatment option for patients with EGFR-mutated NSCLC. The nearly doubled progression-free survival represents a significant clinical advancement in a disease area where extending time to progression is a critical therapeutic goal.
Overall survival data were not mature at the time of analysis, with 75 deaths (41%) in the rezivertinib group and 82 deaths (44%) in the gefitinib group (HR: 0.85; 95% CI: 0.62-1.16; P=0.29). The study remains in follow-up to assess this important secondary endpoint.
The REZOR trial results, published in The Lancet Respiratory Medicine, highlight rezivertinib's potential to address the significant unmet need for more effective first-line therapies in EGFR-mutated NSCLC, a disease that accounts for a substantial proportion of lung cancer cases globally.
