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.

Methods

This multicentre, double-blind, randomised, phase 3 study (REZOR) included eligible patients from 50 hospitals across China.

这项多中心、双盲、随机、III期研究（REZOR）在中国的50家医院中纳入了符合条件的患者。

Those who had been histologically or cytologically confirmed as having NSCLC with EGFR exon 19 deletion or exon 21 Leu858Arg mutation by central laboratory were randomly assigned (1:1) to receive once daily either rezivertinib 180 mg or gefitinib 250 mg, until unacceptable toxicity occurred, disease progression, or other treatment discontinuation criteria were met.

那些通过中心实验室组织学或细胞学确认为非小细胞肺癌伴有EGFR外显子19缺失或外显子21 Leu858Arg突变的患者被随机分配（1:1），每天一次接受rezivertinib 180 mg或gefitinib 250 mg治疗，直到出现不可接受的毒性、疾病进展或其他治疗停药标准达成。

Each cycle lasted for 21 days.

每个治疗周期持续21天。

The primary endpoint was progression-free survivalevaluated by masked independent central review (MICR) in the intention-to-treatset.

主要终点是在意向治疗集中通过蒙面独立中央审查（MICR）评估的无进展生存期。

This trial is registered with ClinicalTrials.gov, NCT03866499 and follow-up is ongoing.

该试验已在ClinicalTrials.gov注册，注册号为NCT03866499，目前随访仍在进行中。

Results

Between July 15, 2019, and Feb 14, 2022, 695 patients were screened.

2019年7月15日至2022年2月14日期间，共有695名患者接受了筛查。

Among them, 369 eligible patients were randomly assigned to receive either rezivertinib 180 mg/day plus placebo (n=184) or gefitinib 250 mg/day plus placebo (n=185) in a 1:1 ratio; all of eligible participants were included in the intention-to-treatset.

在这些患者中，有369名符合条件的患者被随机分配接受rezivertinib 180 mg/天加安慰剂（n=184）或gefitinib 250 mg/天加安慰剂（n=185）的治疗，按照1:1的比例；所有符合条件的参与者都被纳入了意向治疗集。

Median MICR-assessed progression-free survivalwas 19·3 months (95% CI 13·8-22·1) in the rezivertinib group and 9·6 months (8·4-11·3) in the gefitinib group (hazard ratio[HR] 0·48, 95% CI 0·36-0·63; p<0·0001) and the prespecified subgroup efficacy analysis showed consistent results.

在 rezivertinib 组中，MICR 评估的无进展生存期中位数为 19.3 个月（95% 置信区间 13.8-22.1），而在 gefitinib 组中为 9.6 个月（8.4-11.3）（风险比 [HR] 0.48，95% 置信区间 0.36-0.63；p<0.0001），并且预先设定的亚组疗效分析显示了一致的结果。

Median duration of exposure was 16·0 months (95% CI 0·0-29·7) in the rezivertinib group and 11·0 months (0·0-28·9) in the gefitinib group.

rezivertinib 组的平均暴露持续时间为 16.0 个月（95% 置信区间 0.0-29.7），而 gefitinib 组为 11.0 个月（0.0-28.9）。

Grade 3 or higher treatment-emergent adverse events (82 [45%] of 184 in the rezivertinib group; 80 [43%] of 185 in the gefitinib group) and treatment-related adverse events (TRAEs; 43 [23%] of 184 in the rezivertinib group; 43 [23%] of 185 in the gefitinib group) were similar in both groups.

3级或更高级别的治疗后不良事件（rezivertinib组184人中有82人[45%]；gefitinib组185人中有80人[43%]）以及与治疗相关的不良事件（TRAEs；rezivertinib组184人中有43人[23%]；gefitinib组185人中有43人[23%]）在两组中相似。

One patient died from a TRAE in the rezivertinib group, due to pneumonia and interstitial lung disease.

rezivertinib组有一名患者因治疗相关不良事件（TRAE）死亡，死因为肺炎和间质性肺病。

interpretation

Our findings suggested that rezivertinib is a potential choice for patients with EGFR-mutated locally advanced or metastatic NSCLC as first-line therapy, owing to the superior overall efficacy and subgroup progression-free survivalcompared with gefitinib in targeted patients.

我们的发现表明，对于EGFR突变的局部晚期或转移性非小细胞肺癌患者，作为一线治疗，rezivertinib是一个潜在的选择，其总体疗效和特定患者亚组的无进展生存期优于吉非替尼。

No new safety signals were identified.

未发现新的安全信号。

funding

Beta Pharma (Shanghai) and the China National Science and Technology Major Project for Key New Drug Development.

上海贝塔药业与中国国家重点新药开发科技重大专项