PMID- 38061977 OWN - NLM STAT- MEDLINE DCOM- 20240311 LR - 20240409 IS - 1938-0682 (Electronic) IS - 1558-7673 (Linking) VI - 22 IP - 2 DP - 2024 Apr TI - Safety and Efficacy of Second-Line TKI Plus Anti-PD1 in Metastatic Non-Clear Cell Renal Cell Carcinoma: A Real-World Study. PG - 252-260.e3 LID - S1558-7673(23)00253-7 [pii] LID - 10.1016/j.clgc.2023.11.007 [doi] AB - OBJECTIVES: Guidelines recommend clinical trials or tyrosine kinase inhibitor (TKI) as the first-line option for systemic therapy for non-clear cell renal cell carcinoma (nccRCC) with limited efficacy. However, the preferred subsequent options remain unclear when patients progress after first-line treatment. This study aimed to evaluate the efficacy and safety of anti-PD-1 plus TKI therapy as the second-line regimen in nccRCC. PATIENTS AND METHODS: We conducted a retrospective analysis of patients with metastatic nccRCC who failed first-line TKI therapy between October 2011 and September 2020. The baseline characteristics of the patients and adverse events (AEs) were collected. Efficacy measures included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). RESULTS: The current study enrolled 65 patients, with a median age of 48 (interquartile 37-60) years. Among all patients, 21 received TKI monotherapy while 44 patients received combination therapy (TKI plus anti-PD1). The ORR and DCR for the whole cohort were 38.5% and 56.9%, respectively. ORR (50.0% vs. 14.3%, P = .006) and DCR (70.5% vs. 28.6%, P = .001) were improved in the combination group compared with the TKI group. The overall second-line PFS was 7.7 (95% CI: 6.1-9.3) months and OS was 25.2 (19.5-30.8) months. Patients receiving combination therapy had a longer PFS compared with those receiving TKI monotherapy [median PFS (95% CI): 9.2 (5.9-12.4) vs. 5.4 (2.6-8.2) m, Log-rank P = .002]. The incidence of treatment-related AEs of grade 3 or higher was comparable between the 2 groups (56.8% vs. 52.4%). CONCLUSION: Anti-PD-1 plus TKI therapy appeared effective and safe in the treatment of patients with metastatic nccRCC who progressed after first-line TKIs. CI - Copyright (c) 2023 Elsevier Inc. All rights reserved. FAU - Huang, Tingxuan AU - Huang T AD - Department of Urology Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China. FAU - Wang, Jun AU - Wang J AD - Department of Urology Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China. FAU - Liu, Ruiqi AU - Liu R AD - Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. FAU - Wei, Wensu AU - Wei W AD - Department of Urology Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China. FAU - Liu, Yang AU - Liu Y AD - Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. FAU - Zhang, Zhiling AU - Zhang Z AD - Department of Urology Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China. FAU - Guo, Shengjie AU - Guo S AD - Department of Urology Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China. FAU - Han, Hui AU - Han H AD - Department of Urology Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China. FAU - Zhou, Fangjian AU - Zhou F AD - Department of Urology Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China. FAU - He, Liru AU - He L AD - Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. FAU - Dong, Pei AU - Dong P AD - Department of Urology Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China. Electronic address: dongpei@sysucc.org.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20231119 PL - United States TA - Clin Genitourin Cancer JT - Clinical genitourinary cancer JID - 101260955 RN - 0 (Protein Kinase Inhibitors) RN - Clear-cell metastatic renal cell carcinoma SB - IM MH - Humans MH - Adult MH - Middle Aged MH - *Carcinoma, Renal Cell/pathology MH - Retrospective Studies MH - Protein Kinase Inhibitors/adverse effects MH - Progression-Free Survival OTO - NOTNLM OT - Efficacy OT - Immunotherapy OT - Non clear cell renal cell carcinoma OT - Safety OT - Tyrosine kinase inhibitor COIS- Disclosure The authors declare that they have no competing interests. EDAT- 2023/12/08 00:42 MHDA- 2024/03/11 06:42 CRDT- 2023/12/07 22:14 PHST- 2023/09/01 00:00 [received] PHST- 2023/11/11 00:00 [revised] PHST- 2023/11/12 00:00 [accepted] PHST- 2024/03/11 06:42 [medline] PHST- 2023/12/08 00:42 [pubmed] PHST- 2023/12/07 22:14 [entrez] AID - S1558-7673(23)00253-7 [pii] AID - 10.1016/j.clgc.2023.11.007 [doi] PST - ppublish SO - Clin Genitourin Cancer. 2024 Apr;22(2):252-260.e3. doi: 10.1016/j.clgc.2023.11.007. Epub 2023 Nov 19.