Tachibana Yusuke, Morimoto Kenji, Yamada Tadaaki, Kawachi Hayato, Tamiya Motohiro, Negi Yoshiki, Goto Yasuhiro, Nakao Akira, Shiotsu Shinsuke, Tanimura Keiko, Takeda Takayuki, Okada Asuka, Harada Taishi, Date Koji, Chihara Yusuke, Hasegawa Isao, Tamiya Nobuyo, Katayama Yuki, Nishioka Naoya, Iwasaku Masahiro, Tokuda Shinsaku, Kijima Takashi, Takayama Koichi
Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Kyoto, Japan.
Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Osaka, Japan.
Invest New Drugs. 2024 Oct;42(5):538-546. doi: 10.1007/s10637-024-01467-7. Epub 2024 Aug 21.
The association between depth of response (DpR) and treatment outcomes has been documented across various types of cancer. Immune checkpoint inhibitor (ICI)-based treatment is globally used as first-line treatment for non-small cell lung cancer (NSCLC) with programmed death-ligand 1 (PD-L1) expression ≥ 50%. However, in this population, the significance of DpR is not elucidated. Patients with advanced NSCLC and PD-L1 expression ≥ 50% who received ICI-monotherapy or ICI plus chemotherapy were retrospectively enrolled into this study. Treatment responses were grouped into DpR 'quartiles' by percentage of maximal tumor reduction (Q1 = 1-25%, Q2 = 26-50%, Q3 = 51-75%, and Q4 = ≥ 76%), and no tumor reduction (NTR). The association between DpR and survival rates were determined using hazard ratios (HR) generated by the Cox proportional hazards model. The Kaplan-Meier method was used to determine survival outcomes. A total of 349 patients were included, of which 214 and 135 patients received pembrolizumab monotherapy and ICI plus chemotherapy, respectively, as first-line treatments. The majority of the patients were male. All DpR quartiles, especially Q4, showed an association with progression-free survival (PFS)/overall survival (OS). In the Q4 cohort, patients who received pembrolizumab had a longer PFS than those who received ICI plus chemotherapy. High DpR was associated with longer PFS and OS, with a more pronounced effect observed with pembrolizumab monotherapy than with ICI plus chemotherapy.
反应深度（DpR）与治疗结果之间的关联已在各种癌症类型中得到记录。基于免疫检查点抑制剂（ICI）的治疗在全球范围内被用作程序性死亡配体1（PD-L1）表达≥50%的非小细胞肺癌（NSCLC）的一线治疗。然而，在这一人群中，DpR的意义尚未阐明。对接受ICI单药治疗或ICI联合化疗的晚期NSCLC且PD-L1表达≥50%的患者进行了回顾性纳入研究。根据最大肿瘤缩小百分比将治疗反应分为DpR“四分位数”（Q1 = 1-25%，Q2 = 26-50%，Q3 = 51-75%，Q4 =≥76%），以及无肿瘤缩小（NTR）。使用Cox比例风险模型生成的风险比（HR）来确定DpR与生存率之间的关联。采用Kaplan-Meier方法确定生存结果。共纳入349例患者，其中214例和135例患者分别接受帕博利珠单抗单药治疗和ICI联合化疗作为一线治疗。大多数患者为男性。所有DpR四分位数，尤其是Q4，均显示与无进展生存期（PFS）/总生存期（OS）相关。在Q4队列中，接受帕博利珠单抗治疗的患者的PFS长于接受ICI联合化疗的患者。高DpR与更长的PFS和OS相关，与ICI联合化疗相比，帕博利珠单抗单药治疗观察到的效果更显著。
