Clinical outcome after progressing to frontline and second-line Anti-PD-1/PD-L1 in advanced urothelial cancer

被引:45
作者
de Liano Lista, Alfonso Gomez [1 ,2 ]
van Dijk, Nick [3 ]
Oria de Rueda, Guillermo de Velasco [4 ]
Necchi, Andrea [5 ]
Lavaud, Pernelle [6 ]
Morales-Barrera, Rafael [7 ]
Alonso Gordoa, Teresa [8 ]
Maroto, Pablo [9 ]
Ravaud, Alain [10 ]
Duran, Ignacio [11 ]
Szabados, Bernadett [1 ]
Castellano, Daniel [4 ]
Giannatempo, Patrizia [5 ]
Loriot, Yohann [6 ]
Carles, Joan [7 ]
Anguera Palacios, Georgia [9 ]
Lefort, Felix [10 ]
Raggi, Daniele [5 ]
Goupil, Marine Gross [10 ]
Powles, Thomas [1 ]
Van der Heijden, Michiel S. [3 ]
机构
[1] St Bartholomews Hosp, London, England
[2] Complejo Hosp Univ Insular Materno Infantil, Las Palmas Gran Canaria, Spain
[3] Netherlands Canc Inst, Amsterdam, Netherlands
[4] Hosp 12 Octubre, Madrid, Spain
[5] Fdn IRCCS Ist Nazl Tumori, Milan, Italy
[6] Gustave Roussy, Paris, France
[7] Hosp Valle De Hebron, Barcelona, Spain
[8] Hosp Ramon & Cajal, Madrid, Spain
[9] Hosp Santa Creu & Sant Pau, Barcelona, Spain
[10] Ctr Hosp Univ, Bordeaux, France
[11] Hosp Marques de Valdecilla IDIVAL, Santander, Spain
关键词
Urothelial carcinoma; Bladder cancer; Immunotherapy; Immune checkpoint inhibitors; PD-1; PD-L1; CISPLATIN-INELIGIBLE PATIENTS; TRANSITIONAL-CELL CARCINOMA; SINGLE-ARM; MULTICENTER; CHEMOTHERAPY; TRIAL; METHOTREXATE; GEMCITABINE; VINBLASTINE; DOXORUBICIN;
D O I
10.1016/j.eururo.2019.10.004
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Background: Immune checkpoint inhibitors (ICIs) are approved for first-line (cisplatin unfit, PD-L1+) and platinum-refractory urothelial carcinoma (UC). Still, most patients experience progressive disease (PD) as the best response. Although higher response rates to subsequent systemic treatment (SST) have been described, post-PD outcome data are scarce. Objective: To examine the outcome of UC patients who received SST and no SST after progressing to ICIs. Design, setting, and participants: A retrospective analysis of UC patients progressing to frontline or later-line anti-PD-1/PD-L1 therapy in 10 European institutions was conducted between March 2013 and September 2017. Intervention: Post-PD management as per standard practice. Outcome measurements and statistical analysis: Overall survival (OS) was analyzed with a Kaplan-Meier model. Cox regression was used for multivariate analysis (MV). Impact of SST on OS was examined with a time-varying covariate model. Results and limitations: A total of 270 UC patients with PD to ICIs (69 frontline, 201 later line) were analyzed. Of the patients, 57% of frontline-ICI-PD and 34% of later-line-ICI-PD patients received SST, and SST had an impact on OS in MV (frontline: hazard ratio [HR] 0.22, 95% confidence interval [CI] 0.10-0.51, p< 0.001; later line: HR 0.22, 95% CI 0.13-0.36, p< 0.001). In the frontline-ICI-PD group, median OS with and without SST was 6.8 mo (95% CI 5.0-8.6) and 1.9 mo (95% CI 0.9-3.0), respectively. High disease burden (three or more metastatic sites: HR 2.49, p = 0.03; simultaneous liver/bone metastases: HR 3.93, p = 0.03) predicted worse survival. In later-line-ICI-PD group, response to ICIs (HR 0.37, p = 0.03), longer exposure to ICIs (HR 0.89, p = 0.002), and bonemetastasis (HR 2.42, p< 0.001) predicted survival. The retrospective nature of this study and a lack of certain parameters limit the interpretation of our analysis. Conclusions: Patients progressing to frontline ICIs are at risk of early death, excluding them from experiencing potential benefit from chemotherapy Patient summary: Our analysis suggests that outcomes after failing immunotherapy are poor, particularly in UC patients who received no prior chemotherapy. (C) 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:269 / 276
页数:8
相关论文
共 50 条
[41]   Patient selection for anti-PD-1/PD-L1 therapy in advanced non-small-cell lung cancer: implications for clinical practice [J].
Califano, Raffaele ;
Lal, Rohit ;
Lewanski, Conrad ;
Nicolson, Marianne C. ;
Ottensmeier, Christian H. ;
Popat, Sanjay ;
Hodgson, Matthew ;
Postmus, Pieter E. .
FUTURE ONCOLOGY, 2018, 14 (23) :2415-2431
[42]   PD-L1 expression in melanoma shows marked heterogeneity within and between patients: implications for anti-PD-1/PD-L1 clinical trials [J].
Madore, Jason ;
Vilain, Ricardo E. ;
Menzies, Alexander M. ;
Kakavand, Hojabr ;
Wilmott, James S. ;
Hyman, Jessica ;
Yearley, Jennifer H. ;
Kefford, Richard F. ;
Thompson, John F. ;
Long, Georgina V. ;
Hersey, Peter ;
Scolyer, Richard A. .
PIGMENT CELL & MELANOMA RESEARCH, 2015, 28 (03) :245-253
[43]   PD-L1 testing in urothelial bladder cancer: essentials of clinical practice [J].
Mathieu Rouanne ;
Camélia Radulescu ;
Julien Adam ;
Yves Allory .
World Journal of Urology, 2021, 39 :1345-1355
[44]   Response to platinum-based therapies in second-line after immunotherapy in advanced or metastatic non-small-cell lung cancer PD-L1 ≥50% [J].
Olivares-Hernandez, Alejandro ;
Posado-Dominguez, Luis ;
Redondo-Gonzalez, Juan Carlos ;
Corvo-Felix, Laura ;
Hernandez, Lorena Bellido ;
Fonseca-Sanchez, Emilio ;
del Barco-Morillo, Edel .
TRANSLATIONAL LUNG CANCER RESEARCH, 2024, 13 (10) :2649-2659
[45]   Therapeutic Associations Comprising Anti-PD-1/PD-L1 in Breast Cancer: Clinical Challenges and Perspectives [J].
Ledys, Fanny ;
Kalfeist, Laura ;
Galland, Loick ;
Limagne, Emeric ;
Ladoire, Sylvain .
CANCERS, 2021, 13 (23)
[46]   The effect of gender on the clinical outcome of PD-1/PD-L1 inhibitor in advanced lung cancer patients [J].
Wu, Bing ;
Sun, Congcong ;
Sun, Xiaoqin ;
Li, Xue .
MEDICINE, 2023, 102 (34) :E34849
[47]   Clinical and Biological Variables Influencing Outcome in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC) Treated with Anti-PD-1/PD-L1 Antibodies: A Prospective Multicentre Study [J].
Quaquarini, Erica ;
Sottotetti, Federico ;
Agustoni, Francesco ;
Pozzi, Emma ;
Malovini, Alberto ;
Teragni, Cristina Maria ;
Palumbo, Raffaella ;
Saltalamacchia, Giuseppe ;
Tagliaferri, Barbara ;
Balletti, Emanuela ;
Rinaldi, Pietro ;
Canino, Costanza ;
Pedrazzoli, Paolo ;
Bernardo, Antonio .
JOURNAL OF PERSONALIZED MEDICINE, 2022, 12 (05)
[48]   Evaluation of PD-L1 biomarker for immune checkpoint inhibitor (PD-1/PD-L1 inhibitors) treatments for urothelial carcinoma patients: A meta-analysis [J].
Rui, Xin ;
Gu, Ting-Ting ;
Pan, Hua-Feng ;
Zhang, Hui-Zhi .
INTERNATIONAL IMMUNOPHARMACOLOGY, 2019, 67 :378-385
[49]   Hyperprogressive Disease in Patients With Urothelial Carcinoma or Renal Cell Carcinoma Treated With PD-1/PD-L1 Inhibitors [J].
Hwang, Inhwan ;
Park, Inkeun ;
Yoon, Shin-kyo ;
Lee, Jae Lyun .
CLINICAL GENITOURINARY CANCER, 2020, 18 (02) :E122-E133
[50]   The global landscape of neoadjuvant and adjuvant anti-PD-1/PD-L1 clinical trials [J].
Wu, Dawei ;
Huang, Huiyao ;
Zhang, Minghui ;
Li, Ziwei ;
Wang, Shuhang ;
Yu, Yue ;
Fang, Yuan ;
Jiang, Ning ;
Miao, Huilei ;
Ma, Peiwen ;
Tang, Yu ;
Li, Ning .
JOURNAL OF HEMATOLOGY & ONCOLOGY, 2022, 15 (01)