Concomitant medications in patients with metastatic urothelial carcinoma receiving enfortumab vedotin: real-world data from the ARON-2EV study

被引：0

作者：

Fiala, Ondrej ^{[1
,2
,3
]}

Buti, Sebastiano ^{[4
,5
]}

Fujita, Kazutoshi ^{[6
]}

de Liano, Alfonso Gomez ^{[7
]}

Fukuokaya, Wataru ^{[8
]}

Kimura, Takahiro ^{[8
]}

Yanagisawa, Takafumi ^{[8
]}

Giannatempo, Patrizia ^{[9
]}

Angel, Martin ^{[10
]}

Mennitto, Alessia ^{[11
]}

Molina-Cerrillo, Javier

Bourlon, Maria T. ^{[12
]}

Soares, Andrey ^{[13
,14
]}

Takeshita, Hideki ^{[15
]}

Calabro, Fabio ^{[16
]}

Ortega, Cinzia ^{[17
]}

Kucharz, Jakub ^{[18
]}

Milella, Michele ^{[19
]}

Seront, Emmanuel ^{[20
]}

Park, Se Hoon ^{[21
]}

Tural, Deniz ^{[22
]}

Benedetti, Giovanni ^{[23
]}

Urun, Yuksel

Battelli, Nicola ^{[24
]}

Melichar, Bohuslav ^{[25
]}

Poprach, Alexandr ^{[26
,27
]}

Buchler, Tomas ^{[28
,29
]}

Kopecky, Jindrich ^{[30
]}

Conteduca, Vincenza ^{[31
]}

Monteiro, Fernando Sabino Marques ^{[14
,32
]}

Massari, Francesco ^{[33
,34
]}

Gupta, Shilpa ^{[35
]}

Santoni, Matteo ^{[24
]}

机构：

[1] Charles Univ Prague, Fac Med, Dept Oncol & Radiotherapeut, Alej Svobody 80, Plzen 30460, Czech Republic

[2] Charles Univ Prague, Univ Hosp Pilsen, Alej Svobody 80, Plzen 30460, Czech Republic

[3] Charles Univ Prague, Fac Med Pilsen, Biomed Ctr, Plzen, Czech Republic

[4] Univ Hosp Parma, Med Oncol Unit, Parma, Italy

[5] Univ Parma, Dept Med & Surg, Parma, Italy

[6] Kindai Univ, Fac Med, Dept Urol, Osaka, Japan

[7] Complejo Hosp Univ Insular Materno Infantil, Dept Med Oncol, Las Palmas Gran Canaria, Spain

[8] Jikei Univ, Dept Urol, Sch Med, 3-19-18 Nishi Shimbashi,Minato Ku, Tokyo 1058471, Japan

[9] Fdn IRCCS Ist Nazl Tumori, Med Oncol Dept, Via Giacomo Venezian 1, Milan, Italy

[10] Alexander Fleming Inst, Genitourinary Oncol Unit, Clin Oncol, Buenos Aires, Argentina

[11] Azienda Osped Univ Maggiore Della Carit, Dept Med Oncol, Novara, Italy

[12] Mexico Univ Panamer, Escuela Med, Dept Hemato Oncol, Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Mexico City, Mexico

[13] Hosp Israelita Albert Einstein, Sao Paulo, SP, Brazil

[14] Latin Amer Cooperat Oncol Grp LACOG, Porto Alegre, Brazil

[15] Saitama Med Univ, Saitama Med Ctr, Dept Urol, Saitama, Japan

[16] IRCCS Regina Elena Natl Canc Inst, Med Oncol 1, Rome, Italy

[17] Osped Michele E Pietro Ferrero-Verduno CN, Dipartimento Oncol, ASLCN2 Alba E, Bra, Italy

[18] Maria Sklodowska Curie Natl Res Inst Oncol Warsaw, Dept Urooncol, Warsaw, Poland

[19] Univ & Hosp Trust AOUI Verona, Dept Engn Innovat Med DIMI, Sect Innovat Biomed Oncol Area, I-37134 Verona, Italy

[20] Clin Univ St Luc, Dept Med Oncol, Brussels, Belgium

[21] Sungkyunkwan Univ, Samsung Med Ctr, Sch Med, Seoul, South Korea

[22] Koc Univ, Dept Med Oncol, Med Fac, Istanbul, Turkiye

[23] Osped Civitanova Marche, UO Oncol, Civitanova Marche, Italy

[24] Macerata Hosp, Med Oncol Unit, Macerata, Italy

[25] Palacky Univ, Fac Med & Dent, Dept Oncol, Olomouc, Czech Republic

[26] Masaryk Mem Canc Inst, Dept Comprehens Canc Care, Brno 65653, Czech Republic

[27] Masaryk Univ, Fac Med, Dept Comprehens Canc Care, Brno 62500, Czech Republic

[28] Charles Univ Prague, Fac Med 2, Dept Oncol, V Uvalu 84, Prague 15006, Czech Republic

[29] Motol Univ Hosp, V Uvalu 84, Prague 15006, Czech Republic

[30] Univ Hosp Hradec Kralove, Dept Surg, Sokolska 581, Hradec Kralove 50005, Czech Republic

[31] Univ Foggia, Dept Med & Surg Sci, Unit Med Oncol & Biomol Therapy, Policlin Riuniti, Foggia, Italy

[32] Hosp Sirio Libanes, Brasilia, DF, Brazil

[33] IRCCS Azienda Osped Univ Bologna, Med Oncol, Bologna, Italy

[34] Univ Bologna, Dept Med & Surg Sci DIMEC, Bologna, Italy

[35] Cleveland Clin, Taussig Canc Inst, Cleveland, OH USA

来源：

CLINICAL & EXPERIMENTAL METASTASIS | 2025年 / 42卷 / 02期

关键词：

Urothelial cancer; Enfortumab vedotin; Concomitant medication; Antibiotics; Corticosteroids; Concomitant drug score; ARON-2(EV) study; NCT05290038; PROTON PUMP INHIBITORS; GUT MICROBIOME; CANCER; CELL; METABOLISM; MANAGEMENT; OUTCOMES; IMPACT; DRUGS; TUMOR;

D O I：

10.1007/s10585-025-10335-4

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Patients with metastatic urothelial carcinoma (mUC) are typically elderly and often have other comorbidities that require the use of concomitant medications. In our study we evaluated the association of concomitant use of antibiotics (ATBs), proton pump inhibitors (PPIs), corticosteroids, statins, metformin and insulin with patient outcomes and we validated the prognostic role of a concomitant drug score in mUC patients treated with enfortumab vedotin (EV) monotherapy. Data from 436 patients enrolled in the ARON-2(EV) retrospective study were analyzed according to the concomitant medications used at baseline. Finally, the patients were stratified into three risk groups according to the concomitant drug score based on ATBs, corticosteroids and PPIs. Statistical analysis involved Fisher exact test, Kaplan-Meier method, log-rank test, and univariate/multivariate Cox proportional hazard regression models. Inferior survival outcomes were observed in ATB users compared to non-users (OS: 7.3 months, 95%CI 5.0 - 12.3 vs 13.7 months, 95%CI 12.2 - 47.3, p = 0.001; PFS: 5.1 months 95%CI 3.3 - 17.7 vs 8.3 months, 95%CI 7.1 - 47.3, p = 0.001) and also in corticosteroid users compared to non-users (OS: 8.4 months, 95%CI 6.6 - 10.0 vs 14.2 months, 95%CI 12.7 - 47.3, p < 0.001; PFS: 6.0 months 95%CI 4.6 - 7.9 vs 8.9 months, 95%CI 7.2 - 47.3, p = 0.004). In the Cox multivariate analysis, the concomitant drug score was a significant factor predicting both OS (HR = 1.32 [95% CI 1.03 - 1.68], p = 0.026) and PFS (HR = 1.23 [95% CI 1.01 - 1.51], p = 0.044). Our findings suggest detrimental impact of concomitant use of ATBs and corticosteroids on survival outcomes and the prognostic utility of the concomitant drug score in previously treated mUC patients receiving EV.

引用

页数：13

共 45 条

[11] Rizzo A., Santoni M., Mollica V., Ricci A.D., Calabro C., Cusmai A., Et al., The impact of concomitant proton pump inhibitors on immunotherapy efficacy among patients with urothelial carcinoma: a meta-analysis, J Pers Med, 12, 5, (2022)
[12] Fiala O., Buti S., Takeshita H., Okada Y., Massari F., Palacios G.A., Et al., Use of concomitant proton pump inhibitors, statins or metformin in patients treated with pembrolizumab for metastatic urothelial carcinoma: data from the ARON-2 retrospective study, Cancer Immunol Immunother, 72, 11, pp. 3665-3682, (2023)
[13] Maslov D.V., Tawagi K., Kc M., Simenson V., Yuan H., Parent C., Bamnolker A., Goel R., Blake Z., Matrana M.R., Johnson D.H., Timing of steroid initiation and response rates to immune checkpoint inhibitors in metastatic cancer, J Immunother Cancer, 9, 7, (2021)
[14] Bruera S., Suarez-Almazor M.E., The effects of glucocorticoids and immunosuppressants on cancer outcomes in checkpoint inhibitor therapy, Front Oncol, 23, 12, (2022)
[15] Buti S., Bersanelli M., Perrone F., Et al., Effect of concomitant medications with immune-Modulatory properties on the outcomes of patients with advanced cancer treated with immune checkpoint inhibitors: development and validation of a novel prognostic index, Eur J Cancer, 142, pp. 18-28, (2021)
[16] Buti S., Bersanelli M., Perrone F., Et al., Predictive ability of a drug-based score in patients with advanced non-small-cell lung cancer receiving first-line Immunotherapy, Eur J Cancer, 150, pp. 224-231, (2021)
[17] Takada K., Buti S., Bersanelli M., Et al., Antibiotic-dependent effect of probiotics in patients with non-small cell lung cancer treated with PD-1 checkpoint blockade, Eur J Cancer, 172, pp. 199-208, (2022)
[18] Buti S., Basso U., Giannarelli D., Et al., Concomitant drugs Prognostic score in patients with metastatic renal cell carcinoma receiving Ipilimumab and Nivolumab in the compassionate use program in Italy: brief communication, J Immunother, 46, pp. 22-26, (2023)
[19] Taguchi S., Kawai T., Buti S., Et al., Validation of a drug-based score in advanced urothelial carcinoma treated with Pembrolizumab, Immunotherapy, 15, pp. 827-837, (2023)
[20] Schwartz L.H., Litiere S., de Vries E., Ford R., Gwyther S., Mandrekar S., Et al., RECIST 1.1-update and clarification: from the RECIST committee, Eur J Cancer, 62, pp. 132-137, (2016)

← 1 2 3 4 5 →