Xiong Longbin, Shan Xingli, Ma Huali, Guo Shengjie, Liu Jiyan, Chen Xianda, Meng Wenjun, Guo Bin, Jiang Lijuan, Yan Ru, An Xin, Shi Yanxia, Zhang Yijun, Xue Ting, Wei Lichao, Xu Daming, Zhang Zhiling, Qin Zike, Yao Kai, Li Yajian, Spiess Philippe E, Hu Linjun, Xing Nianzeng, Han Hui
Department of Urology, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
State Key Laboratory of Oncology in Southern China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
J Natl Compr Canc Netw. 2024 Dec 20;23(1):e247074. doi: 10.6004/jnccn.2024.7074.
The purpose of this study was to evaluate the efficacy and safety of PD-1 blockade combined with cisplatin and paclitaxel (TP)-based chemotherapy as first-line treatment for advanced penile squamous cell carcinoma (PSCC).
A retrospective review was performed of 32 eligible patients with high-risk stage IV (cN3M0-1) PSCC who received first-line PD-1 blockade combined with TP-based chemotherapy at 5 medical centers (2019-2023). Clinical responses were assessed using RECIST version 1.1. Treatment-related adverse events (TrAEs) and postsurgical complications were graded according to CTCAE version 5.0. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Multiplex immunofluorescence was used to explore potential biomarkers and to present the tumor microenvironment landscape before and after treatment.
After a median treatment duration of 4 cycles (range, 2-6), the overall objective response rate was 78.1% (25/32). Among 27 patients with locally advanced PSCC, 13 (48.1%) subsequently underwent consolidative surgery and 6 (22.2%) achieved a pathologic complete response (pCR). Additionally, 8 (25.0%) patients in the overall cohort underwent consolidated radiotherapy. Median follow-up was 21.1 months (95% CI, 14.1-42.7). Median PFS and OS were 15.0 months (95% CI, 11.4-not available [NA]) and 19.3 months (95% CI, 16.7-NA), respectively. All patients experienced TrAEs, with 50% (16/32) of them having grade ≥3 TrAEs. Higher intratumoral CD8+ T-cell infiltration was observed in pretreatment samples of responders compared with nonresponders (P=.03). CD4+ T-cells, natural killer cells, and macrophages, among others, exhibited significant changes after treatment (all P<.05), suggesting their potential involvement in the antitumor response to immunochemotherapy.
PD-1 blockade plus TP-based chemotherapy was effective and well tolerated, with favorable survival outcomes for patients with stage IV PSCC. High pretreatment intratumoral CD8+ T-cell infiltration may help to identify potential responders.
本研究旨在评估程序性死亡蛋白1（PD-1）阻断剂联合顺铂和紫杉醇（TP）为基础的化疗作为晚期阴茎鳞状细胞癌（PSCC）一线治疗方案的疗效和安全性。
对5家医学中心（2019 - 2023年）32例符合条件的高危IV期（cN3M0 - 1）PSCC患者进行回顾性分析，这些患者接受了一线PD-1阻断剂联合TP为基础的化疗。采用实体瘤疗效评价标准（RECIST）1.1版评估临床反应。根据美国国立癌症研究所不良事件通用术语标准（CTCAE）5.0版对治疗相关不良事件（TrAEs）和术后并发症进行分级。采用Kaplan-Meier法估计无进展生存期（PFS）和总生存期（OS）。采用多重免疫荧光法探索潜在生物标志物，并呈现治疗前后的肿瘤微环境特征。
中位治疗周期为4个周期（范围2 - 6个周期），总体客观缓解率为78.1%（25/32）。在27例局部晚期PSCC患者中，13例（48.1%）随后接受了巩固性手术，6例（22.2%）达到病理完全缓解（pCR）。此外，总体队列中有8例（25.0%）患者接受了巩固性放疗。中位随访时间为21.1个月（95%置信区间，14.1 - 42.7）。中位PFS和OS分别为15.0个月（95%置信区间，11.4 - 未获得数据[NA]）和19.3个月（95%置信区间，16.7 - NA）。所有患者均经历了TrAEs，其中50%（16/32）为≥3级TrAEs。与无反应者相比，反应者治疗前样本中肿瘤内CD8 + T细胞浸润更高（P = 0.03）。治疗后，CD4 + T细胞、自然杀伤细胞和巨噬细胞等出现显著变化（均P < 0.05），提示它们可能参与了免疫化疗的抗肿瘤反应。
PD-1阻断剂联合TP为基础化疗有效且耐受性良好，对IV期PSCC患者有良好的生存结局。治疗前肿瘤内CD8 + T细胞浸润较高可能有助于识别潜在反应者。
