Hata Tae, Yamada Tadaaki, Goto Yasuhiro, Amano Akihiko, Negi Yoshiki, Watanabe Satoshi, Furuya Naoki, Oba Tomohiro, Ikoma Tatsuki, Nakao Akira, Tanimura Keiko, Taniguchi Hirokazu, Yoshimura Akihiro, Fukui Tomoya, Murata Daiki, Kaira Kyoichi, Shiotsu Shinsuke, Hibino Makoto, Okada Asuka, Chihara Yusuke, Kawachi Hayato, Kijima Takashi, Takayama Koichi
Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Clin Lung Cancer. 2025 May;26(3):e190-e198.e4. doi: 10.1016/j.cllc.2025.01.002. Epub 2025 Jan 4.
Although chemoimmunotherapy is recommended for advanced nonsquamous non-small cell lung cancer (NSCLC) with low programmed cell death ligand 1 (PD-L1) expression, no head-to-head comparisons of immune checkpoint inhibitors (ICIs) have been performed. Therefore, we compared the effect and safety of regimens in these patients to guide evidence-based treatment.
This retrospective study included patients with advanced nonsquamous NSCLC with a PD-L1 tumor proportion score of 1% to 49% administered ICI combination platinum-based chemotherapy between May 2018 and May 2023 at 19 institutions in Japan. The main analysis compared survival outcomes and the incidence of grade ≥3 adverse events among regimens.
Among 316 included patients (median [range] age, 69 [36-89] years; 242 males; 41 never smokers), 200 (63%), 68 (22%), and 48 (15%) received chemotherapy combined with anti-programmed cell death protein 1 (PD-1), anti-PD-L1, and anti-PD-1/cytotoxic T-lymphocyte associated protein 4 (CTLA-4) antibodies, respectively. The median overall survival times were 28.6, 23.1, and 24.4 months (P = .41), and the median progression-free survival times were 9.4, 7.2, and 8.7 months (P = .28) in the anti-PD-1/Chemo, anti-PD-L1/Chemo and anti-PD-1/CTLA-4/Chemo groups, respectively. The anti-PD-1/CTLA-4/Chemo group had the lowest incidence of hematologic toxicity (P = .13) and the highest incidence of nonhematologic toxicity (P = .07). The incidence of grade ≥3 pneumonitis was significantly lower in the anti-PD-L1/Chemo group (P = .049).
Despite comparable survival benefits, adverse events differed among three regimens in patients with low PD-L1 expression. Notably, anti-PD-L1 antibody combination chemotherapy may reduce the risk of severe pneumonitis.
尽管对于程序性细胞死亡配体1（PD-L1）低表达的晚期非鳞状非小细胞肺癌（NSCLC）推荐采用化疗免疫疗法，但尚未对免疫检查点抑制剂（ICI）进行直接比较。因此，我们比较了这些患者中不同治疗方案的疗效和安全性，以指导循证治疗。
这项回顾性研究纳入了2018年5月至2023年5月期间在日本19家机构接受ICI联合铂类化疗的PD-L1肿瘤比例分数为1%至49%的晚期非鳞状NSCLC患者。主要分析比较了不同治疗方案之间的生存结局和≥3级不良事件的发生率。
在纳入的316例患者中（中位[范围]年龄，69[36 - 89]岁；242例男性；41例从不吸烟者），分别有200例（63%）、68例（22%）和48例（15%）接受了化疗联合抗程序性细胞死亡蛋白1（PD-1）、抗PD-L1和抗PD-1/细胞毒性T淋巴细胞相关蛋白4（CTLA-4）抗体治疗。抗PD-1/化疗、抗PD-L1/化疗和抗PD-1/CTLA-4/化疗组的中位总生存时间分别为28.6、23.1和24.4个月（P = 0.41），中位无进展生存时间分别为9.4、7.2和8.7个月（P = 0.28）。抗PD-1/CTLA-4/化疗组血液学毒性发生率最低（P = 0.13），非血液学毒性发生率最高（P = 0.07）。抗PD-L1/化疗组≥3级肺炎的发生率显著更低（P = 0.049）。
尽管三种治疗方案的生存获益相当，但PD-L1低表达患者中不同方案的不良事件存在差异。值得注意的是，抗PD-L1抗体联合化疗可能降低严重肺炎的风险。
