Hirano Satoshi, Fujita Tetsuo, Takahashi Hidekazu, Noda Kento, Yoshida Naoki, Matsuda Kosei, Shojima Hikaru, Shikano Kohei, Amano Hiroyuki, Nakamura Makoto, Onozawa Masakatsu, Araki Hitoshi, Aruga Takashi, Nakamura Sukeyuki
Department of Medical Oncology, Funabashi Municipal Medical Center, Chiba, Japan.
Department of Respiratory Medicine, Funabashi Municipal Medical Center, Chiba, Japan.
Chin Clin Oncol. 2025 Jun;14(3):29. doi: 10.21037/cco-25-3.
The introduction of immune checkpoint inhibitors (ICIs) has enabled long-term survival for non-small cell lung cancer (NSCLC) patients. However, the proportion of patients achieving this is still low compared to patients with melanoma. Many NSCLC patients experience early progression (primary resistance) following ICI treatment, or relapse after initial responses (acquired resistance). While chemotherapy regimens, typically involving cytotoxic agents, are commonly used after ICI resistance, little evidence has been accumulated regarding the efficacy of ICI rechallenge. The aim of this study was to evaluate the efficacy of ICI rechallenge in patients who experienced failure of primary treatment with ICI-containing regimens. Additionally, we assessed whether the administration of local therapy prior to rechallenge influenced the efficacy of ICI rechallenge.
We retrospectively reviewed the records of advanced NSCLC patients for whom response was evaluated as progressive disease (PD) after receiving an ICI-containing regimen as first-line therapy and underwent rechallenge with an ICI in Funabashi Municipal Medical Center between January 2020 and March 2024. We analyzed progression-free survival (PFS) and overall survival (OS) based on whether local therapy (including beyond PD with local therapy) was performed. PFS was compared using the Kaplan-Meier method, with statistical significance set at P<0.05 using log-rank testing.
The study included 20 patients, with 10 patients in the local therapy group and 10 in the no-local therapy group. No significant differences in patient characteristics were apparent between groups, although the no-local therapy group tended to show a higher number of organs with residual metastases at the time of rechallenge. When ICI rechallenge was administered after local therapy, median PFS was significantly longer in the local therapy group (9.0 months) than in the no-local therapy group (1.6 months, P=0.02), particularly in cases where radiation therapy was applied to the primary lesion just before rechallenge. However, no significant difference in OS was evident between the local treatment group (21.4 months) and the no-local treatment group (18.8 months; P=0.12).
Rechallenge with ICI following local therapy in NSCLC patients who developed resistance to ICIs may extend PFS, suggesting potential value as a therapeutic option.
免疫检查点抑制剂（ICI）的引入使非小细胞肺癌（NSCLC）患者能够长期生存。然而，与黑色素瘤患者相比，实现长期生存的患者比例仍然较低。许多NSCLC患者在ICI治疗后会出现早期进展（原发性耐药），或在初始缓解后复发（获得性耐药）。虽然在ICI耐药后通常使用化疗方案（通常涉及细胞毒性药物），但关于ICI再次挑战的疗效的证据积累较少。本研究的目的是评估ICI再次挑战对接受含ICI方案一线治疗失败的患者的疗效。此外，我们评估了再次挑战前给予局部治疗是否会影响ICI再次挑战的疗效。
我们回顾性分析了2020年1月至2024年3月期间在船桥市立医疗中心接受含ICI方案一线治疗后疗效评估为疾病进展（PD）并接受ICI再次挑战的晚期NSCLC患者的记录。我们根据是否进行了局部治疗（包括局部治疗后疾病进展）分析了无进展生存期（PFS）和总生存期（OS）。使用Kaplan-Meier方法比较PFS，使用对数秩检验将统计学显著性设定为P<0.05。
该研究包括20例患者，局部治疗组10例，非局部治疗组10例。两组患者的特征没有明显差异，尽管非局部治疗组在再次挑战时往往有更多残留转移器官。在局部治疗后进行ICI再次挑战时，局部治疗组的中位PFS（9.0个月）明显长于非局部治疗组（1.6个月，P=0.02），特别是在再次挑战前对原发灶进行放射治疗的情况下。然而，局部治疗组（21.4个月）和非局部治疗组（18.8个月；P=0.12）之间的OS没有明显差异。
对ICI产生耐药的NSCLC患者在局部治疗后进行ICI再次挑战可能会延长PFS，提示其作为一种治疗选择的潜在价值。
