Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, China.
Department of Medical Oncology, Cancer Hospital Chinese Academy of Medical Science, Shenzhen Center, Shenzhen, China.
Lung Cancer. 2023 Sep;183:107288. doi: 10.1016/j.lungcan.2023.107288. Epub 2023 Jul 4.
To evaluate the long-term safety and efficacy of atezolizumab monotherapy in Chinese patients with previously treated, locally advanced or metastatic non-small cell lung cancer (NSCLC).
In this open-label, single-arm, multicenter study, patients received atezolizumab 1200 mg intravenously on Day 1 of each 21-day cycle. The primary endpoint was incidence of atezolizumab-related serious adverse events (SAEs). Secondary endpoints included other safety and efficacy measures. Patients with available tumor tissue and blood samples underwent biomarker analyses. Patients with available tumor biopsies underwent exome sequencing.
The safety and evaluable populations included 101 and 97 patients, respectively. Exome sequencing data were available for 31 patients. Median follow-up time was 27.43 months. Atezolizumab-related SAEs and immune-related adverse events occurred in 25.7% and 47.5% of the safety population, respectively, and in the following subgroups: central nervous system metastases (n = 14), 35.7% and 35.7%; squamous NSCLC (n = 39), 33.3% and 53.8%. The 24-month overall survival rate was 37.4%. Median overall survival and progression-free survival by RECIST v1.1 were 15.31 and 2.86 months, respectively; objective response rate was 16.5% in the evaluable population. PRRC2C (odds ratio: 12.780, P = 0.014) and ZMYND8 (odds ratio: 19.963, P = 0.016) gene mutations were significantly enriched in atezolizumab responders vs non-responders. Patients with CD8 TILs > 10% vs ≤ 10% were significantly more likely to be atezolizumab responders.
No new safety concerns were raised, and clinically meaningful benefits of atezolizumab monotherapy were shown. The results of the biomarker analyses may guide future therapeutic strategies.
评估阿特珠单抗单药治疗既往接受过治疗的局部晚期或转移性非小细胞肺癌（NSCLC）中国患者的长期安全性和疗效。
在这项开放标签、单臂、多中心研究中，患者每 21 天周期的第 1 天接受阿特珠单抗 1200mg 静脉输注。主要终点是阿特珠单抗相关严重不良事件（SAE）的发生率。次要终点包括其他安全性和疗效措施。有可用肿瘤组织和血液样本的患者进行了生物标志物分析。有可用肿瘤活检样本的患者进行了外显子组测序。
安全性和可评估人群分别包括 101 名和 97 名患者。可评估人群中有 31 名患者可提供外显子组测序数据。中位随访时间为 27.43 个月。安全性人群中，阿特珠单抗相关 SAE 和免疫相关不良事件的发生率分别为 25.7%和 47.5%，且以下亚组中也有发生：中枢神经系统转移（n=14），35.7%和 35.7%；鳞状非小细胞肺癌（n=39），33.3%和 53.8%。24 个月总生存率为 37.4%。根据 RECIST v1.1，中位总生存期和无进展生存期分别为 15.31 个月和 2.86 个月，可评估人群的客观缓解率为 16.5%。PRRC2C（比值比：12.780，P=0.014）和 ZMYND8（比值比：19.963，P=0.016）基因突变在阿特珠单抗应答者与无应答者中明显富集。肿瘤浸润 CD8 TILs＞10%与≤10%的患者更有可能是阿特珠单抗应答者。
未发现新的安全性问题，并显示出阿特珠单抗单药治疗具有临床意义的获益。生物标志物分析的结果可能指导未来的治疗策略。
