替雷利珠单抗联合化疗用于 EGFR 酪氨酸激酶抑制剂治疗进展的 - 突变型非鳞状非小细胞肺癌患者。
Tislelizumab plus chemotherapy for patients with -mutated non-squamous non-small cell lung cancer who progressed on EGFR tyrosine kinase inhibitor therapy.
机构信息
Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
出版信息
J Immunother Cancer. 2023 Aug;11(8). doi: 10.1136/jitc-2023-006887.
BACKGROUND
Treatment options are limited for epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) after treatment failure with EGFR tyrosine kinase inhibitors (TKIs). This multicenter open-label, phase II study aims to evaluate the efficacy and safety of tislelizumab plus chemotherapy (cohort 1, TIS+chemo) or tislelizumab plus chemotherapy and bevacizumab (cohort 2, TIS+chemo+ beva) in EGFR-mutated non-squamous NSCLC patients who progressed on EGFR TKI therapies. Here, the primary analysis of the TIS+chemo cohort is reported.
METHODS
In the TIS+chemo cohort, patients with EGFR-sensitizing mutations with prior EGFR TKI failure received tislelizumab plus carboplatin and nab-paclitaxel as induction treatment, followed by maintenance with tislelizumab plus pemetrexed. The primary endpoint was 1-year progression-free survival (PFS) rate. The planned sample size was 66 with a historical control of 7%, an expected value of 20%, a one-sided α of 0.05, and a power of 85%.
RESULTS
Between July 11, 2020 and December 13, 2021, 69 patients were enrolled. As of June 30, 2022, the median follow-up was 8.2 months. Among the 62 patients in the efficacy analysis set, estimated 1-year PFS rate was 23.8% (90% CI 13.1% to 36.2%), and its lower bound of 90% CI was higher than the historical control of chemotherapy (7%), which met the primary endpoint. The median PFS was 7.6 (95% CI 6.4 to 9.8) months. Median overall survival (OS) was not reached (95% CI 14.0 to not estimable), with a 1-year OS rate of 74.5% (95% CI 56.5% to 86.0%). The objective response rate and disease control rate were 56.5% (95% CI 43.3% to 69.0%) and 87.1% (95% CI 76.1% to 94.3%), respectively. Patients who had progressed on first-generation/second-generation and third-generation EGFR-TKIs at baseline had shorter PFS than those who progressed on first-generation/second-generation EGFR-TKIs (median 7.5 vs 9.8 months, p=0.031). Patients with positive ctDNA had shorter PFS (median 7.4 vs 12.3 months, p=0.031) than those with negative ctDNA. No grade 5 treatment-emergent adverse events (TEAEs) were observed. Grades 3-4 TEAEs occurred in 40.6% (28/69) of patients. Grades 3-4 immune-related AEs occurred in 5 (7.2%) patients.
CONCLUSION
The study met the primary endpoint for the TIS+chemo cohort. Tislelizumab plus chemotherapy is effective with an acceptable safety profile for -mutated non-squamous NSCLC after EGFR TKI failure.
背景
表皮生长因子受体（EGFR）突变型非小细胞肺癌（NSCLC）患者在接受 EGFR 酪氨酸激酶抑制剂（TKI）治疗失败后，治疗选择有限。本多中心、开放标签、II 期研究旨在评估替雷利珠单抗联合化疗（队列 1，TIS+chemo）或替雷利珠单抗联合化疗和贝伐珠单抗（队列 2，TIS+chemo+beva）在 EGFR 突变型非鳞状 NSCLC 患者中的疗效和安全性，这些患者在 EGFR TKI 治疗后进展。这里报告了 TIS+chemo 队列的主要分析结果。
方法
在 TIS+chemo 队列中，既往 EGFR TKI 失败且存在 EGFR 敏感突变的患者接受替雷利珠单抗联合卡铂和白蛋白紫杉醇作为诱导治疗，随后使用替雷利珠单抗联合培美曲塞维持治疗。主要终点是 1 年无进展生存期（PFS）率。计划样本量为 66 例，历史对照为 7%，预期值为 20%，单侧α为 0.05，功效为 85%。
结果
2020 年 7 月 11 日至 2021 年 12 月 13 日期间，共纳入 69 例患者。截至 2022 年 6 月 30 日，中位随访时间为 8.2 个月。在疗效分析集的 62 例患者中，估计 1 年 PFS 率为 23.8%（90%CI，13.1%至 36.2%），其 90%CI 的下限高于化疗的历史对照（7%），达到了主要终点。中位 PFS 为 7.6 个月（95%CI，6.4 至 9.8）。中位总生存期（OS）未达到（95%CI，14.0 至无法评估），1 年 OS 率为 74.5%（95%CI，56.5%至 86.0%）。客观缓解率和疾病控制率分别为 56.5%（95%CI，43.3%至 69.0%）和 87.1%（95%CI，76.1%至 94.3%）。基线时第一代/第二代和第三代 EGFR-TKI 进展的患者 PFS 短于第一代/第二代 EGFR-TKI 进展的患者（中位 PFS，7.5 与 9.8 个月，p=0.031）。ctDNA 阳性的患者 PFS 较短（中位 PFS，7.4 与 12.3 个月，p=0.031）。未观察到 5 级治疗相关不良事件（TEAEs）。69 例患者中有 40.6%（28/69）发生 3-4 级 TEAEs。5 例（7.2%）患者发生 3-4 级免疫相关 AEs。
结论
该研究达到了 TIS+chemo 队列的主要终点。替雷利珠单抗联合化疗在 EGFR TKI 治疗失败后的 EGFR 突变型非鳞状 NSCLC 患者中具有疗效，且安全性可接受。
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