Department of Respiratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Department of Internal Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Sci Rep. 2019 Mar 12;9(1):4278. doi: 10.1038/s41598-019-40748-7.
To summarize the therapeutic effects of PD-1/PD-L1 inhibitors on patients with advanced non-small cell lung cancer (NSCLC) in a real-world setting, we attempted to identify potential molecular biomarkers or clinical factors that reflected the therapeutic effect. The medical records of patients with non-small cell lung cancer who were treated with PD-1/PD-L1 inhibitors were obtained from the outpatient department or inpatient department of Peking Union Medical College Hospital from August 1, 2015, to January 1, 2018. Our follow-up continued until May 1,2018. We chose overall survival (OS) as the primary observation endpoint and progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety as the secondary observation endpoints. Efficacy was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The Kaplan-Meier method was used to generate survival curves, and we compared the influence of different factors on PFS and OS by the log-rank test. The median follow-up time was 11 months. At the end of the follow-up, 24 patients (61.5%) were still undergoing immunotherapy, and 7 patients (17.9%) had died. Twenty-six cases (66.7%) employed PD-1/PD-L1 inhibitors as first-line treatment, and 7 cases (17.9%) employed PD-1/PD-L1 inhibitors as second-line treatment. Only 6 cases (15.4%) employed PD-1/PD-L1 inhibitors as third-line treatment. Therapeutic effect evaluation: Complete response (CR): 1 case (2.6%). Partial response (PR): 10 cases (25.6%). Stable disease (SD): 16 cases (41.0%). Progressive disease (PD): 12 cases (30.8%). The ORR was 28.2%, and DCR was 69.2%. The median PFS was 25.5 months (95% CI 6.8-44.1 months), which failed to reach the median OS. PD-1/PD-L1 inhibitor treatment is more effective for advanced non-small cell lung cancer patients in a real-world setting than in clinical trials; PD-1/PD-L1 inhibitor treatment is more effective for people who are over 70 than for people who are under 70. Additionally, patients who are over 75 years old have a higher response rate, suggesting that elderly patients may receive more benefits from immunotherapy; Patients who have an epidermal growth factor receptor (EGFR) mutation (+) may benefit from immunotherapy after treatment with a tyrosine kinase inhibitor (TKI). It is essential to identify these potential patients from the entire patient pool; PD-1 may have a certain curative effect on brain metastases from NSCLC. Local radiotherapy may help to improve PD-1 intracranial efficacy.
为了总结 PD-1/PD-L1 抑制剂在真实世界环境下治疗晚期非小细胞肺癌（NSCLC）患者的疗效，我们试图确定反映治疗效果的潜在分子生物标志物或临床因素。我们从北京协和医院的门诊或住院部获取了 2015 年 8 月 1 日至 2018 年 1 月 1 日期间接受 PD-1/PD-L1 抑制剂治疗的非小细胞肺癌患者的病历。我们的随访持续到 2018 年 5 月 1 日。我们选择总生存期（OS）作为主要观察终点，无进展生存期（PFS）、客观缓解率（ORR）、疾病控制率（DCR）和安全性作为次要观察终点。疗效根据实体瘤反应评价标准（RECIST）1.1 进行评价。采用 Kaplan-Meier 法生成生存曲线，通过对数秩检验比较不同因素对 PFS 和 OS 的影响。中位随访时间为 11 个月。随访结束时，24 例（61.5%）患者仍在接受免疫治疗，7 例（17.9%）患者死亡。26 例（66.7%）患者采用 PD-1/PD-L1 抑制剂作为一线治疗，7 例（17.9%）患者采用 PD-1/PD-L1 抑制剂作为二线治疗。仅 6 例（15.4%）患者采用 PD-1/PD-L1 抑制剂作为三线治疗。疗效评价：完全缓解（CR）：1 例（2.6%）。部分缓解（PR）：10 例（25.6%）。疾病稳定（SD）：16 例（41.0%）。疾病进展（PD）：12 例（30.8%）。ORR 为 28.2%，DCR 为 69.2%。中位 PFS 为 25.5 个月（95%CI 6.8-44.1 个月），未能达到中位 OS。PD-1/PD-L1 抑制剂治疗在真实世界环境下对晚期非小细胞肺癌患者比临床试验更有效；PD-1/PD-L1 抑制剂治疗对 70 岁以上患者比 70 岁以下患者更有效。此外，75 岁以上患者的缓解率更高，提示老年患者可能从免疫治疗中获益更多；有表皮生长因子受体（EGFR）突变（+）的患者在接受酪氨酸激酶抑制剂（TKI）治疗后可能受益于免疫治疗。从整个患者群体中识别这些潜在患者至关重要；PD-1 对非小细胞肺癌脑转移可能有一定的疗效。局部放疗可能有助于提高 PD-1 的颅内疗效。
