Yin Guisen, Liu Xin, Yu Xiangtao, Tan Song, Liu Fen
Department of Pharmacy, Yantai Hospital of Traditional Chinese Medicine, Yantai, 264000, Shandong, China.
Department of Oncology, Yantai Hospital of Traditional Chinese Medicine, Yantai, 264000, Shandong, China.
Sci Rep. 2025 Jan 2;15(1):30. doi: 10.1038/s41598-024-83947-7.
Immune checkpoint inhibitors (ICIs) plus chemotherapy have become the standard of care for first-line treatment of advanced non-small cell lung cancer (NSCLC) with EGFR/ALK negative. However, there is no clear second-line treatment option after first-line treatment failure. To investigate the efficacy and safety of ICIs alone or in combination rechallenge treatment after first-line ICIs plus chemotherapy progression in advanced NSCLC. We retrospectively analyzed the cases of patients who received ICIs alone or in combination rechallenge treatment after first-line ICIs plus chemotherapy progression in advanced NSCLC at Hunan Cancer Hospital between January 2020 and May 2024. We evaluated the effects of continued immunotherapy on patients' objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and adverse events after first-line treatment progression, and analyzed the relationship between outcomes and clinical characteristics. A total of 154 patients were included, with 146 patients developing resistance, 8 patients showing no progression. The ORR was 16.44%, the DCR was 68.49%, and the median PFS was 4.6 months. Patients treated with the new immune drug therapy had longer PFS than those treated with the original immunotherapy (5.0 months vs. 3.7 months, p = 0.0438). The PFS in patients receiving ICIs plus targeted therapy was significantly longer than that in patients who receiving ICIs alone, chemo-ICIs plus targeted therapy and ICIs plus chemotherapy (chemo-ICIs) (5.7 months vs. 3.6 months vs3.2 months vs. 2.9 months, p = 0.0086). Multivariate analysis showed that treatment regimen was a risk factor for immune rechallenge PFS, but there was no statistical correlation between gender, age, smoking history, pathological type, intermittent treatment or first-line drug resistance and immune rechallenge PFS. Our findings suggest that selecting ICIs plus targeted therapy may improve PFS in patients with advanced NSCLC after first-line chemo-ICIs progression. while replacement with new BSAb/PD-1 may be more beneficial to patients. However, there is a lack of large sample randomized controlled studies and evidence-based medical evidence, and more clinical studies are needed to further confirm.
免疫检查点抑制剂（ICIs）联合化疗已成为表皮生长因子受体（EGFR）/间变性淋巴瘤激酶（ALK）阴性的晚期非小细胞肺癌（NSCLC）一线治疗的标准方案。然而，一线治疗失败后尚无明确的二线治疗选择。为了探究晚期NSCLC患者在一线ICIs联合化疗进展后单独使用ICIs或联合再挑战治疗的疗效和安全性。我们回顾性分析了2020年1月至2024年5月期间在湖南省肿瘤医院接受一线ICIs联合化疗进展后单独使用ICIs或联合再挑战治疗的晚期NSCLC患者的病例。我们评估了一线治疗进展后继续免疫治疗对患者客观缓解率（ORR）、疾病控制率（DCR）、无进展生存期（PFS）和不良事件的影响，并分析了疗效与临床特征之间的关系。共纳入154例患者，其中146例出现耐药，8例未进展。ORR为16.44%，DCR为68.49%，中位PFS为4.6个月。接受新型免疫药物治疗的患者PFS长于接受原免疫治疗的患者（5.0个月对3.7个月，p = 0.0438）。接受ICIs联合靶向治疗的患者PFS显著长于单独接受ICIs、化疗-ICIs联合靶向治疗和ICIs联合化疗（化疗-ICIs）的患者（5.7个月对3.6个月对3.2个月对2.9个月，p = 0.0086）。多因素分析显示治疗方案是免疫再挑战PFS的危险因素，但性别、年龄、吸烟史、病理类型、间断治疗或一线耐药与免疫再挑战PFS之间无统计学相关性。我们的研究结果表明，对于一线化疗-ICIs进展后的晚期NSCLC患者，选择ICIs联合靶向治疗可能改善PFS。而更换为新型双特异性抗体（BSAb）/程序性死亡受体1（PD-1）可能对患者更有益。然而，缺乏大样本随机对照研究和循证医学证据，需要更多的临床研究进一步证实。
