Saal Jonas, Eckstein Markus, Ritter Manuel, Brossart Peter, Luetkens Julian, Ellinger Jörg, Grünwald Viktor, Hölzel Michael, Klümper Niklas
Medical Clinic III for Oncology, Hematology, Immune-Oncology and Rheumatology, University Hospital Bonn, Bonn, Germany.
Institute of Experimental Oncology, University Hospital Bonn, Bonn, Germany.
JAMA Oncol. 2025 Feb 1;11(2):154-161. doi: 10.1001/jamaoncol.2024.5672.
Progressive disease (PD) in patients treated with immune checkpoint inhibitors (ICIs) varies widely in outcomes according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. Efforts to modify RECIST for ICI treatment have not resolved the heterogeneity in PD patterns, posing a clinical challenge.
To develop and validate a modified PD classification based on PD patterns and evaluate its association with postprogression survival (PPOS) in patients treated with the programmed cell death protein ligand 1 antibody atezolizumab across various solid tumors.
DESIGN, SETTING, AND PARTICIPANTS: This study analyzed data from 5 phase 3 trials (IMmotion151, IMvigor211, OAK, Impower133, and IMspire150) involving patients treated with atezolizumab for renal cell carcinoma (RCC), urothelial carcinoma, small cell lung cancer, non-small cell lung cancer, and melanoma. This post hoc analysis was conducted from March to September 2024.
Treatment with atezolizumab.
The primary outcome was the association of PD patterns with PPOS. Seven PD patterns were identified based on the enlargement of target and nontarget lesions or new lesions and their combinations.
A total of 1377 patients were analyzed across the 5 trials. In RCC, 7 PD patterns significantly affected prognosis. The 6-month PPOS probability ranged from 26% for progression in target and nontarget lesions plus new lesions to 90% for progression in either target or nontarget lesions alone. A modified PD classification was developed that categorized PD into 3 risk levels: low risk (progression of existing lesions), intermediate risk (new lesions without progression of existing lesions), and high risk (progression of existing lesions plus new lesions). This score was associated with PPOS in ICI-treated RCC, with hazard ratios of 0.23 (95% CI, 0.13-0.41; P < .001) and 0.39 (95% CI, 0.23-0.66; P < .001) for low-risk and intermediate-risk PD compared with high-risk PD, respectively. Validation in additional trials confirmed the score's applicability across various tumors.
In this study, a survival score was developed based on PD patterns. The risk classification was associated with PPOS across various solid tumors treated with immunotherapy and may therefore enhance prognostication and clinical decision-making, potentially providing a valuable tool for treating patients with PD who are receiving immunotherapy.
根据实体瘤疗效评价标准（RECIST）1.1版，接受免疫检查点抑制剂（ICI）治疗的患者中，疾病进展（PD）的结局差异很大。针对ICI治疗对RECIST进行修改的努力尚未解决PD模式的异质性，这构成了一项临床挑战。
基于PD模式开发并验证一种改良的PD分类方法，并评估其与接受程序性细胞死亡蛋白配体1抗体阿替利珠单抗治疗的各种实体瘤患者进展后生存期（PPOS）的相关性。
设计、设置和参与者：本研究分析了5项3期试验（IMmotion151、IMvigor211、OAK、Impower133和IMspire150）的数据，这些试验涉及接受阿替利珠单抗治疗的肾细胞癌（RCC）、尿路上皮癌、小细胞肺癌、非小细胞肺癌和黑色素瘤患者。这项事后分析于2024年3月至9月进行。
接受阿替利珠单抗治疗。
主要结局是PD模式与PPOS的相关性。根据靶病灶和非靶病灶的增大或新病灶及其组合，确定了7种PD模式。
5项试验共分析了1377例患者。在RCC中，7种PD模式显著影响预后。6个月PPOS概率范围为：靶病灶和非靶病灶加新病灶进展时为26%，仅靶病灶或非靶病灶进展时为90%。开发了一种改良的PD分类方法，将PD分为3个风险级别：低风险（现有病灶进展）、中风险（新病灶且现有病灶无进展）和高风险（现有病灶进展加新病灶）。该评分与接受ICI治疗的RCC患者的PPOS相关，低风险和中风险PD与高风险PD相比，风险比分别为0.23（95%CI，0.13 - 0.41；P <.001）和0.39（95%CI，0.23 - 0.66；P <.001）。在其他试验中的验证证实了该评分在各种肿瘤中的适用性。
在本研究中，基于PD模式开发了一种生存评分。该风险分类与接受免疫治疗的各种实体瘤患者的PPOS相关，因此可能会增强预后评估和临床决策， potentially为治疗接受免疫治疗的PD患者提供一个有价值的工具。 （最后一句原文中“potentially”翻译时位置微调了一下，使表达更通顺）
