Background: 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). Patients and Methods: 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. Results: 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. Conclusions: 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.
Submitted July 19, 2024; final revision received September 10, 2024; accepted for publication September 17, 2024. Published online December 20, 2024.
L. Xiong, X. Shan, H. Ma, S. Guo, and J. Liu are co–first authors.
L. Hu, N. Xing, and H. Han are co–last authors.
Author contributions: Conceptualization: Xiong, Shan, S. Guo, Liu, Spiess, Hu, Xing, Han. Data curation: Shan, S. Guo, Chen, Meng, B. Guo, Jiang, Yan, An, Shi, Y. Zhang, Xue, Wei, Xu, Qin, Yao, Li. Formal analysis: Xiong. Funding acquisition: Han. Investigation: Xiong, Ma, Y. Zhang. Methodology: Xiong, Shan, Ma, S. Guo, Y. Zhang, Z. Zhang, Spiess, Hu, Han. Project administration: Liu, Hu, Xing, Han. Resources: Shan, S. Guo, Liu, Chen, Meng, B. Guo, Jiang, Yan, An, Shi, Xue, Wei, Xu, Qin, Yao, Li, Hu, Xing, Han. Software: Xiong. Supervision: Liu, Hu, Han. Validation: S. Guo. Visualization: Xiong, Ma. Writing—original draft: Xiong, Han. Writing—review & editing: Xiong, Z. Zhang, Spiess, Han.
Data availability statement: The study data underlying the findings of current work were deposited at the Research Data Deposit platform (available at http://www.researchdata.org.cn/).
Disclosures: The authors have disclosed that they have not received any financial considerations from any person or organization to support the preparation, analysis, results, or discussion of this article.
Funding: This work was supported by funding from Natural Science Foundation of Guangdong Province (No. 2021A1515220182, 2022A1515012321).
Supplementary material: Supplementary material associated with this article is available online at https://doi.org/10.6004/jnccn.2024.7074. The supplementary material has been supplied by the author(s) and appears in its originally submitted form. It has not been edited or vetted by JNCCN. All contents and opinions are solely those of the author. Any comments or questions related to the supplementary materials should be directed to the corresponding author.