[NEJ026]比较贝伐珠单抗联合厄洛替尼对比厄洛替尼单药一线治疗EGFR突变NSCLC
NEJ026 研究，您如何看待 A+T 组的 PFS 数据
EGFR突变的治疗是肺癌近二十年的重大突破，它使患者生存时间延长，但是在所有患者的治疗中不可避免的出现耐药。总体而言，一代EGFR-TKI总体PFS在9到13个月，为延长患者的PFS，许多临床试验将EGFR-TKI与其它药物联合，其中一个重要的方案是将EGFR-TKI与抗血管生成联合，这就是今天所说的A+T。A+T的III期临床研究是由日本牵头做的全球临床试验，今年公布的结果PFS达到16.9个月，比对照组整整延长3个月，这是令人振奋的信息。这也证实了联合用药可以延缓肿瘤的进展，延长患者生存时间，这就是这个研究的意义。
目前对于A+T方案比较大的质疑与疑问就是联合抗血管生成药之后是否增加毒性，是否值得这个代价，今天公布的III期临床试验结果显示，虽然联合用药比EGFR-TKI单药的毒性略高，但没有发现特殊的毒性事件，且毒性反应是可处理的。
A+T方案的应用为一线治疗增加了治疗选择，年轻患者及无高血压的患者推荐A+T方案的治疗。但需注意的是这是A+T的第一个III期临床试验，我们非常期望中国A+T的试验结果，通过这个结果可以比较在中国环境中和日本环境下的差异以及相同之处。这个模式是不是能够重复，这是我们非常期待的。如果能够相互印证成立，A+T方案将是未来非常好的治疗选择。
NEJ026: Final overall survival analysis of bevacizumab plus erlotinib treatment for NSCLC patients harboring activating EGFR-mutations.
First Author: Makoto Maemondo, Iwate Medical University, Morioka, Japan
Background: In NEJ026, a phase III trial comparing bevacizumab plus erlotinib (BE) to erlotinib monotherapy (E) for EGFR-mutated non-smallcell lung cancer (NSCLC), we demonstrated the progression-free survival (PFS) of BE was significantly superior to E (Saito et al. Lancet Oncol. 2019 May;20(5):625-635.). However overall survival analysis were immature at the cutoff date.
Methods: Chemotherapy-na¨ıve pts with advanced non-squamous NSCLC harboring EGFR-mutation were randomly assigned to receive either combination with erlotinib (150 mg daily) plus bevacizumab (15 mg/kg iv q3w) or erlotinib (150 mg daily). The primary endpoint was PFS. Secondary endpoints were OS, RR, safety, and QoL.
Results: The 226 pts were assigned to BE (n=112) and E (n=114). For the follow-up OS analysis, the data cut-off date was 30 November 2019. Median follow up time was 39.2 months. Median OS was 50.7 months (95% CI, 37.3 months to not reached) with BE and 46.2 months (95%CI, 38.2 months to not reached) with E (hazard ratio, 1.00; 95% CI, 0.68 to 1.48). Twenty-nine patients (25.9%) in BE and twenty-six patients (23.2%) in E were treated by osimertinib as second line treatment. The median survival time between enrollment and progressive disease of second-line treatment (median PFS2) was 28.6 months (95% CI, 22.1 months to 35.9) with BE and 24.3 months (95% CI, 20.4 months to 29.1 months) with E (hazard ratio, 0.80; 95% CI, 0.59 to 1.10). In both arms, the median OS of patients with osimertinib second-line treatment were longer than other second-line chemotherapy groups [50.7 months (95% CI, 38.0 months to 50.7 months) vs 40.1 months (95% CI, 29.5 months to not reached), (hazard ratio, 0.645; 95% CI, 0.40 to 1.03), respectively.
Conclusion: The additional effect of bevacizumab on erlotinib monotherapy for NSCLC with EGFR mutations gradually decreased in the order of PFS2 and survival, with no significant differences.
