Savolitinib plus osimertinib in epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer with MET overexpression and/or amplification following disease progression on osimertinib: primary results from the phase II SAVANNAH study.

We report the primary analysis of the phase II SAVANNAH study (NCT03778229) evaluating savolitinib plus osimertinib in this setting.

我们报告了II期SAVANNAH研究(NCT03778229)的初步分析结果，该研究评估了在上述情况下使用萨沃替尼联合奥希替尼的疗效。

patients_and_methods

Patients had EGFR-mutated, advanced NSCLC with MET overexpression and/or amplification.

患者患有EGFR突变的晚期非小细胞肺癌，伴有MET过表达和/或扩增。

MET cut-offs were initially MET immunohistochemistry (IHC)3+/≥50% (3+ intensity in ≥50% of tumor cells) and/or FISH5+ (≥5 MET gene copies or MET/chromosome 7 centromere ratio ≥2), and increased to MET IHC3+/≥90% and/or FISH10+ after a preliminary analysis.

MET的临界值最初为MET免疫组化(IHC)3+/≥50%（在≥50%的肿瘤细胞中为3+强度）和/或FISH5+（≥5个MET基因拷贝或MET/染色体7着丝粒比例≥2），并在初步分析后提高到MET IHC3+/≥90%和/或FISH10+。

Patients received oral savolitinib [300 mg twice daily (b.i.d.) or once daily (o.d.), or 600 mg o.d.] plus osimertinib 80 mg o.d., or savolitinib 300 mg b.i.d. plus placebo.

患者接受口服萨沃替尼[每日两次300毫克或每日一次300毫克或每日一次600毫克]加上奥希替尼每日一次80毫克，或萨沃替尼每日两次300毫克加上安慰剂。

A primary endpoint was investigator-assessed objective response rate(ORR) in patients with progression on first-line osimertinib and MET IHC3+/≥90% and/or FISH10+ status receiving savolitinib 300 mg b.i.d. plus osimertinib (primary efficacy population).

主要终点是研究者评估的客观缓解率（ORR），在一线奥希替尼治疗进展且MET IHC3+/≥90%和/或FISH10+状态的患者中，接受萨沃替尼每日两次300毫克加上奥希替尼治疗（主要疗效人群）。

Safety was analyzed in all patients receiving savolitinib plus osimertinib.

所有接受萨沃替尼联合奥希替尼治疗的患者均进行了安全性分析。

Results

Of the 365 patients treated, 341 received savolitinib plus osimertinib, with 80 of these included in the primary efficacy population.

在治疗的365名患者中，有341名接受了萨沃替尼联合奥希替尼治疗，其中80名被纳入主要疗效人群。

Investigator-assessed confirmed ORR in the primary efficacy population was 56.3% [95% confidence interval(CI) 44.7% to 67.3%]; the median duration of response (mDoR) was 7.1 months (95% CI 5.6-9.6 months); the median progression-free survival(PFS) was 7.4 months (95% CI 5.5-7.6 months).

研究者评估的主要疗效人群的确认客观缓解率(ORR)为56.3% [95% 置信区间 (CI) 44.7% 至 67.3%]；反应持续时间的中位数(mDoR)为7.1个月 (95% CI 5.6-9.6个月)；无进展生存期(PFS)的中位数为7.4个月 (95% CI 5.5-7.6个月)。

Blinded independent central review was consistent: confirmed ORR 55.0% (95% CI 43.5% to 66.2%); mDoR 9.9 months (95% CI 6.0-13.7 months); median PFS 7.5 months (95% CI 6.4-11.3 months).

盲法独立中心评审结果一致：确认ORR为55.0% (95% CI 43.5% 至 66.2%)；mDoR为9.9个月 (95% CI 6.0-13.7个月)；中位PFS为7.5个月 (95% CI 6.4-11.3个月)。

The most common any grade adverse events in patients receiving savolitinib plus osimertinib were peripheral edema (46.0%), nausea (40.5%), and diarrhea (23.2%).

在接受萨沃替尼加奥希替尼治疗的患者中，最常见的任何级别的不良事件是外周水肿（46.0%）、恶心（40.5%）和腹泻（23.2%）。

Conclusions

Savolitinib 300 mg b.i.d. plus osimertinib demonstrated high, clinically meaningful and durable responses in patients with EGFR-mutated, advanced NSCLC with MET IHC3+/≥90% and/or FISH10+ status following progression on first-line osimertinib.

萨沃替尼300毫克每日两次联合奥希替尼在EGFR突变的晚期NSCLC患者中显示出高、临床意义重大且持久的反应，这些患者在一线使用奥希替尼治疗后进展，并且具有MET IHC3+/≥90%和/或FISH10+状态。

The combination was well tolerated and may provide a new oral targeted treatment approach in this setting.

这种联合疗法耐受性良好，并可能为这一领域提供一种新的口服靶向治疗方案。