Introduction

Acquired resistance to TKI is an important unmet need in the management of EGFR mutated lung cancer. Recent clinical trial IMPower150 suggested that combination approach with VEGF inhibitor, check point inhibitor immunotherapy and platinum-based chemotherapy was effective in oncogene driven lung cancer. The current trial examined the efficacy of a modified regimen in an EGFR mutated cohort.

Methods

An open-labelled, single arm, phase II study was conducted in patients with EGFR mutated NSCLC who had progressed on at least one EGFR TKI. For those with T790M mutation, radiological progression on osimertinib was required for enrolment. Patients were treated with combination atezolizumab (1200 mg), bevacizumab (7.5 mg/kg), pemetrexed (500 mg/m2) and carboplatin (AUC 5) given once every 3 weeks until progression.

Results

Forty patients were enrolled. Median age was 62 (range 45–76) years. More than one half (23/40, 57.5%) had progressed on osimertinib. PD-L1 expression was < 1% in 52.5%. Median follow-up time was 17.8 months. ORR was 62.5%. Median PFS was 9.4 months (95% CI: 7.6 – 12.1). One year OS was 72.5% (95% CI: 0.56–0.83). Treatment related grade 3 or above adverse events (AE) occurred in 37.5% (15/40). Immune-related AE occurred in 32.5% (13/40) patients. Quality of life measures of function and symptoms did not change significantly throughout the course of treatments. Post-trial rechallenge with EGFR TKI containing regimen resulted in PFS of 5.8 months (95% CI 3.9–10.0 months).

Conclusion

Combination approach of atezolizumab, bevacizumab, pemetrexed and carboplatin achieved promising efficacy in metastatic EGFR mutated NSCLC after TKI failure. The results were comparable with taxane based regimen of IMPower150 while toxicity profile was improved.

中文翻译：

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联合阿特珠单抗、贝伐珠单抗、培美曲塞和卡铂治疗 TKI 失败后转移性 EGFR 突变的 NSCLC

介绍

对 TKI 的获得性耐药是 EGFR 突变肺癌管理中一个重要的未满足需求。最近的临床试验 IMPower150 表明，结合 VEGF 抑制剂、检查点抑制剂免疫疗法和铂类化疗对癌基因驱动的肺癌有效。目前的试验检查了改良方案在 EGFR 突变队列中的疗效。

方法

一项开放标记、单臂、II 期研究在 EGFR 突变的 NSCLC 患者中进行，这些患者至少在一种 EGFR TKI 上出现进展。对于那些有 T790M 突变的患者，需要接受奥希替尼的放射学进展才能入组。患者接受联合阿特珠单抗（1200 毫克）、贝伐珠单抗（7.5 毫克/千克）、培美曲塞（500 毫克/平方米）和卡铂（AUC 5）每 3 周给药一次直至进展。

结果

招募了 40 名患者。中位年龄为 62（范围 45-76）岁。超过一半 (23/40, 57.5%) 在奥希替尼治疗中取得进展。52.5% 的 PD-L1 表达 < 1%。中位随访时间为 17.8 个月。ORR 为 62.5%。中位 PFS 为 9.4 个月（95% CI：7.6 – 12.1）。一年 OS 为 72.5%（95% CI：0.56-0.83）。治疗相关的 3 级或以上不良事件 (AE) 发生率为 37.5% (15/40)。32.5% (13/40) 的患者发生了免疫相关 AE。在整个治疗过程中，功能和症状的生活质量测量没有显着变化。试验后再次使用含有 EGFR TKI 的方案导致 PFS 为 5.8 个月（95% CI 3.9-10.0 个月）。

结论

Atezolizumab、贝伐珠单抗、培美曲塞和卡铂的联合治疗在 TKI 失败后转移性 EGFR 突变的 NSCLC 中取得了有希望的疗效。结果与基于紫杉烷的 IMPower150 方案相当，同时毒性特征得到改善。