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.

Humans Proton Pump Inhibitors Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use Metformin / therapeutic use Carcinoma, Transitional Cell Retrospective Studies Urinary Bladder Neoplasms
ARON-2 study Immunotherapy Metformin Proton pump inhibitors Statins Urothelial cancer

Journal

Cancer immunology, immunotherapy : CII
ISSN: 1432-0851
Titre abrégé: Cancer Immunol Immunother
Pays: Germany
ID NLM: 8605732

Informations de publication

Date de publication:
Nov 2023
Historique:
received: 04 05 2023
accepted: 03 08 2023
medline: 23 10 2023
pubmed: 7 9 2023
entrez: 7 9 2023
Statut: ppublish

Résumé

Concomitant medications may potentially affect the outcome of cancer patients. In this sub-analysis of the ARON-2 real-world study (NCT05290038), we aimed to assess the impact of concomitant use of proton pump inhibitors (PPI), statins, or metformin on outcome of patients with metastatic urothelial cancer (mUC) receiving second-line pembrolizumab. We collected data from the hospital medical records of patients with mUC treated with pembrolizumab as second-line therapy at 87 institutions from 22 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall response rate. We carried out a survival analysis by a Cox regression model. A total of 802 patients were eligible for this retrospective study; the median follow-up time was 15.3 months. PPI users compared to non-users showed inferior PFS (4.5 vs. 7.2 months, p = 0.002) and OS (8.7 vs. 14.1 months, p < 0.001). Concomitant PPI use remained a significant predictor of PFS and OS after multivariate Cox analysis. The use of statins or metformin was not associated with response or survival. Our study results suggest a significant prognostic impact of concomitant PPI use in mUC patients receiving pembrolizumab in the real-world context. The mechanism of this interaction warrants further elucidation.

Sections du résumé

BACKGROUND BACKGROUND
Concomitant medications may potentially affect the outcome of cancer patients. In this sub-analysis of the ARON-2 real-world study (NCT05290038), we aimed to assess the impact of concomitant use of proton pump inhibitors (PPI), statins, or metformin on outcome of patients with metastatic urothelial cancer (mUC) receiving second-line pembrolizumab.
METHODS METHODS
We collected data from the hospital medical records of patients with mUC treated with pembrolizumab as second-line therapy at 87 institutions from 22 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall response rate. We carried out a survival analysis by a Cox regression model.
RESULTS RESULTS
A total of 802 patients were eligible for this retrospective study; the median follow-up time was 15.3 months. PPI users compared to non-users showed inferior PFS (4.5 vs. 7.2 months, p = 0.002) and OS (8.7 vs. 14.1 months, p < 0.001). Concomitant PPI use remained a significant predictor of PFS and OS after multivariate Cox analysis. The use of statins or metformin was not associated with response or survival.
CONCLUSIONS CONCLUSIONS
Our study results suggest a significant prognostic impact of concomitant PPI use in mUC patients receiving pembrolizumab in the real-world context. The mechanism of this interaction warrants further elucidation.

Identifiants

DOI: 10.1007/s00262-023-03518-z PMID: 37676282
pubmed: 37676282
doi: 10.1007/s00262-023-03518-z
pii: 10.1007/s00262-023-03518-z
doi:

Substances chimiques

Proton Pump Inhibitors 0
Hydroxymethylglutaryl-CoA Reductase Inhibitors 0
Metformin 9100L32L2N
pembrolizumab DPT0O3T46P

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

3665-3682

Informations de copyright

© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Références

Taguchi S, Kawai T, Nakagawa T, Miyakawa J, Kishitani K, Sugimoto K et al (2022) Improved survival in real-world patients with advanced urothelial carcinoma: a multicenter propensity score-matched cohort study comparing a period before the introduction of pembrolizumab (2003–2011) and a more recent period (2016–2020). Int J Urol 29(12):1462–1469. https://doi.org/10.1111/iju.15014
doi: 10.1111/iju.15014 pubmed: 35996761 pmcid: 10087413
Bellmunt J, de Wit R, Vaughn DJ, Fradet Y, Lee JL, Fong L et al (2017) KEYNOTE-045 investigators. Pembrolizumab as second-line therapy for advanced urothelial carcinoma. N Engl J Med 376(11):1015–1026. https://doi.org/10.1056/NEJMoa1613683
doi: 10.1056/NEJMoa1613683 pubmed: 28212060 pmcid: 5635424
Peters S, Dziadziuszko R, Morabito A, Felip E, Gadgeel SM, Cheema P et al (2018) Atezolizumab versus chemotherapy in patients with platinum treated locally advanced or metastatic urothelial carcinoma (IMvigor211): a multicentre, open-label, phase 3 randomised controlled trial. Lancet 28(9):1831–1839. https://doi.org/10.1038/s41591-022-01933-w
doi: 10.1038/s41591-022-01933-w
Sharma P, Retz M, Siefker-Radtke A, Baron A, Necchi A, Bedkeet J et al (2017) Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicenter, single-arm, phase 2 trial. Lancet Oncol 18(3):312–322. https://doi.org/10.1016/S1470-2045(17)30065-7
doi: 10.1016/S1470-2045(17)30065-7 pubmed: 28131785
Patel MR, Ellerton J, Infante JR, Agrawal M, Gordon M, Aljumailyet R et al (2018) Avelumab in metastatic urothelial carcinoma after platinum failure (JAVELIN Solid Tumor): pooled results from two expansion cohorts of an open-label, phase 1 trial. Lancet Oncol 19(1):51–64. https://doi.org/10.1016/S1470-2045(17)30900-2
doi: 10.1016/S1470-2045(17)30900-2 pubmed: 29217288
Buti S, Bersanelli M, Perrone F, Tiseo M, Tucci M, Adamo V et al (2021) 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 142:18–28. https://doi.org/10.1016/j.ejca.2020.09.033
doi: 10.1016/j.ejca.2020.09.033 pubmed: 33212418
Buti S, Bersanelli M, Perrone F, Bracarda S, Di Maio M, Giusti R et al (2021) Predictive ability of a drug-based score in patients with advanced non-small-cell lung cancer receiving first-line immunotherapy. Eur J Cancer 150:224–231. https://doi.org/10.1016/j.ejca.2021.03.041
doi: 10.1016/j.ejca.2021.03.041 pubmed: 33934059
Takada K, Buti S, Bersanelli M, Shimokawa M, Takamori S, Matsubara T et al (2022) Antibiotic-dependent effect of probiotics in patients with non-small cell lung cancer treated with PD-1 checkpoint blockade. Eur J Cancer 172:199–208. https://doi.org/10.1016/j.ejca.2022.06.002
doi: 10.1016/j.ejca.2022.06.002 pubmed: 35780526
Hopkins AM, Kichenadasse G, Karapetis CS, Rowland A, Sorich MJ (2020) Concomitant antibiotic use and survival in urothelial carcinoma treated with atezolizumab. Eur Urol 78(4):540–543. https://doi.org/10.1016/j.eururo.2020.06.061
doi: 10.1016/j.eururo.2020.06.061 pubmed: 32660748
Hopkins AM, Kichenadasse G, Karapetis CS, Rowland A, Sorich MJ (2020) Concomitant proton pump inhibitor use and survival in urothelial carcinoma treated with atezolizumab. Clin Cancer Res 26:5487–5493
doi: 10.1158/1078-0432.CCR-20-1876 pubmed: 32933995
Ruiz-BañobreJ M-DA, Fernández-Calvo O, Fernández-Núñez N, Medina-Colmenero A, Santomé L et al (2021) Rethinking prognostic factors in locally advanced or metastatic urothelial carcinoma in the immune checkpoint blockade era: a multicenter retrospective study. ESMO Open 6(2):100090. https://doi.org/10.1016/j.esmoop.2021.100090
doi: 10.1016/j.esmoop.2021.100090
Ishiyama Y, Kondo T, Nemoto Y, Kobari Y, Ishihara H, Tachibana H et al (2021) Antibiotic use and survival of patients receiving pembrolizumab for chemotherapy-resistant metastatic urothelial carcinoma. Urol Oncol 39(12):834.e21-834.e28. https://doi.org/10.1016/j.urolonc.2021.05.033
doi: 10.1016/j.urolonc.2021.05.033 pubmed: 34284929
Fukuokaya W, Kimura T, Komura K, Uchimoto T, Nishimura K, Yanagisawa T et al (2022) Effectiveness of pembrolizumab in patients with urothelial carcinoma receiving proton pump inhibitors. Urol Oncol 40(7):346.e1-346.e8. https://doi.org/10.1016/j.urolonc.2022.02.020
doi: 10.1016/j.urolonc.2022.02.020 pubmed: 35346571
Tomisaki I, Harada M, Minato A, Nagata Y, Kimuro R, Higashijima K et al (2022) Impact of the use of proton pump inhibitors on pembrolizumab effectiveness for advanced urothelial carcinoma. Anticancer Res 42(3):1629–1634. https://doi.org/10.21873/anticanres.15638
doi: 10.21873/anticanres.15638 pubmed: 35220261
Kunimitsu Y, Morio K, Hirata S, Yamamoto K, Yamamoto K, Omura T, Hara T et al (2022) Effects of proton pump inhibitors on survival outcomes in patients with metastatic or unresectable urothelial carcinoma treated with pembrolizumab. Biol Pharm Bull 45(5):590–595. https://doi.org/10.1248/bpb.b21-00939
doi: 10.1248/bpb.b21-00939 pubmed: 35491164
Okuyama Y, Hatakeyama S, Numakura K, Narita T, Tanaka T, Miura Y et al (2021) Prognostic impact of proton pump inhibitors for immunotherapy in advanced urothelial carcinoma. BJUI Compass 3:154–161. https://doi.org/10.1002/bco2.118
doi: 10.1002/bco2.118 pubmed: 35474728 pmcid: 8988833
Rizzo A, Santoni M, Mollica V, Ricci AD, Calabrò C, Cusmai A et al (2022) The impact of concomitant proton pump inhibitors on immunotherapy efficacy among patients with urothelial carcinoma: a meta-analysis. J Pers Med 12(5):842. https://doi.org/10.3390/jpm12050842
doi: 10.3390/jpm12050842 pubmed: 35629263 pmcid: 9145929
Triadafilopoulos G, Roorda AK, Akiyama J (2013) Indications and safety of proton pump inhibitor drug use in patients with cancer. Expert Opin Drug Saf 12(5):659–672. https://doi.org/10.1517/14740338.2013.797961
doi: 10.1517/14740338.2013.797961 pubmed: 23647006
Chalabi M, Cardona A, Nagarkar DR, Scala AD, Gandara DR, Rittmeyer A et al (2020) Efficacy of chemotherapy and atezolizumab in patients with non-small-cell lung cancer receiving antibiotics and proton pump inhibitors: pooled post hoc analyses of the OAK and POPLAR trials. Ann Oncol 31(4):525–531. https://doi.org/10.1016/j.annonc.2020.01.006
doi: 10.1016/j.annonc.2020.01.006 pubmed: 32115349
Jackson MA, Goodrich JK, Maxan ME, Freedberg DE, Abrams JA, Poole AC et al (2016) Proton pump inhibitors alter the composition of the gut microbiota. Gut 65(5):749–756. https://doi.org/10.1136/gutjnl-2015-310861
doi: 10.1136/gutjnl-2015-310861 pubmed: 26719299
Deng R, Zhang H, Li Y, Shi Y (2022) Effect of antacid use on immune checkpoint inhibitors in advanced solid cancer patients: a systematic review and meta-analysis. J Immunother 46(2):43–55. https://doi.org/10.1097/CJI.0000000000000442
doi: 10.1097/CJI.0000000000000442 pubmed: 36301729
Ciccarese C, Iacovelli R, Buti S, Primi F, Astore S, Massari F et al (2022) Concurrent nivolumab and metformin in diabetic cancer patients: is it safe and more active? Anticancer Res 42(3):1487–1493. https://doi.org/10.21873/anticanres.15620
doi: 10.21873/anticanres.15620 pubmed: 35220243
Santoni M, Molina-Cerrillo J, Myint ZW, Massari F, Buchler T, Buti S et al (2022) Concomitant use of statins, metformin, or proton pump inhibitors in patients with advanced renal cell carcinoma treated with first-line combination therapies. Target Oncol 17(5):571–581. https://doi.org/10.1007/s11523-022-00907-9
doi: 10.1007/s11523-022-00907-9 pubmed: 35947324
Santoni M, Massari F, Matrana MR, Basso U, De Giorgi U, Aurilio G et al (2022) Statin use improves the efficacy of nivolumab in patients with advanced renal cell carcinoma. Eur J Cancer 172:191–198. https://doi.org/10.1016/j.ejca.2022.04.035
doi: 10.1016/j.ejca.2022.04.035 pubmed: 35780525
Perrone F, Minari R, Bersanelli M, Bordi P, Tiseo M, Favari E et al (2020) The prognostic role of high blood cholesterol in advanced cancer patients treated with immune checkpoint inhibitors. J Immunother 43(6):196–203. https://doi.org/10.1097/CJI.0000000000000321
doi: 10.1097/CJI.0000000000000321 pubmed: 32404654
Cantini L, Pecci F, Hurkmans DP, Belderbos RA, Lanese A, Copparoni C et al (2021) High-intensity statins are associated with improved clinical activity of PD-1 inhibitors in malignant pleural mesothelioma and advanced non-small cell lung cancer patients. Eur J Cancer 144:41–48. https://doi.org/10.1016/j.ejca.2020.10.031
doi: 10.1016/j.ejca.2020.10.031 pubmed: 33326868
Schwartz LH, Litière S, de Vries E, Ford R, Gwyther S, Mandrekar S et al (2016) RECIST 1.1-update and clarification: from the RECIST committee. Eur J Cancer 62:132–137. https://doi.org/10.1016/j.ejca.2016.03.081
doi: 10.1016/j.ejca.2016.03.081 pubmed: 27189322 pmcid: 5737828
Mollica V, Rizzo A, Montironi R, Cheng L, Giunchi F, Schiavina R et al (2020) Current strategies and novel therapeutic approaches for metastatic urothelial carcinoma. Cancers (Basel) 12(6):1449. https://doi.org/10.3390/cancers12061449
doi: 10.3390/cancers12061449 pubmed: 32498352
Routy B, Le Chatelier E, Derosa L, Duong CPM, Alou MT, Daillère R et al (2018) Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science 359(6371):91–97. https://doi.org/10.1126/science.aan3706
doi: 10.1126/science.aan3706 pubmed: 29097494
Seto CT, Jeraldo P, Orenstein R, Chia N, DiBaise JK (2014) Prolonged use of a proton pump inhibitor reduces microbial diversity: implications for Clostridium difficile susceptibility. Microbiome 2:42. https://doi.org/10.1186/2049-2618-2-42
doi: 10.1186/2049-2618-2-42 pubmed: 25426290 pmcid: 4242847
Clooney AG, Bernstein CN, Leslie WD, Vagianos K, Sargent M, Laserna-Mendieta EJ et al (2016) A comparison of the gut microbiome between long-term users and non-users of proton pump inhibitors. Aliment Pharmacol Ther 43(9):974–984. https://doi.org/10.1111/apt.13568
doi: 10.1111/apt.13568 pubmed: 26923470
Tsuda A, Suda W, Morita H, Takanashi K, Takagi A, Koga Y et al (2015) Influence of proton-pump inhibitors on the luminal microbiota in the gastrointestinal tract. Clin Transl Gastroenterol 6(6):e89. https://doi.org/10.1038/ctg.2015.20
doi: 10.1038/ctg.2015.20 pubmed: 26065717 pmcid: 4816248
Imhann F, Bonder MJ, Vich Vila A, Fu J, Mujagic Z, Vork L et al (2016) Proton pump inhibitors affect the gut microbiome. Gut 65(5):740–748. https://doi.org/10.1136/gutjnl-2015-310376
doi: 10.1136/gutjnl-2015-310376 pubmed: 26657899
Thouvenin J, Martínez Chanzá N, Alhalabi O, Lang H, Tannir NM, Barthélémy P et al (2021) Efficacy of immune checkpoint inhibitors in upper tract urothelial carcinomas: current knowledge and future directions. Cancers (Basel) 13(17):4341. https://doi.org/10.3390/cancers13174341
doi: 10.3390/cancers13174341 pubmed: 34503152
Su X, Lu X, Bazal SK, Compérat E, Mouawad R, Yao H et al (2021) Comprehensive integrative profiling of upper tract urothelial carcinomas. Genome Biol 22(1):7. https://doi.org/10.1186/s13059-020-02230-w
doi: 10.1186/s13059-020-02230-w pubmed: 33397444 pmcid: 7780630
Taguchi S, Kawai T, Buti S, Bersanelli M, Uemura Y, Kishitani K, et al (2023) Validation of a drug-based score in advanced urothelial carcinoma treated with pembrolizumab. https://doi.org/10.2217/imt-2023-0028 .
Chan KK, Oza AM, Siu LL (2003) The statins as anticancer agents. Clin Cancer Res 9:10–19
pubmed: 12538446
Keyomarsi K, Sandoval L, Band V (2003) Synchronization of tumor and normal cells from G1 to multiple cell cycles by lovastatin. Cancer Res 9:10–19
Wong WW, Dimitroulakos J, Minden MD, Penn LZ (2002) HMG-CoA reductase inhibitors and the malignant cell: the statin family of drugs as triggers of tumor-specific apoptosis. Leukemia 16:508–519
doi: 10.1038/sj.leu.2402476 pubmed: 11960327
Ferro M, Marchioni M, Lucarelli G, Vartolomei MD, Soria F, Terracciano D et al (2021) Association of statin use and oncological outcomes in patients with first diagnosis of T1 high grade non-muscle invasive urothelial bladder cancer: results from a multicenter study. Minerva Urol Nephrol 73(6):796–802. https://doi.org/10.23736/S2724-6051.20.04076-X
doi: 10.23736/S2724-6051.20.04076-X pubmed: 33439571
Haimerl L, Strobach D, Mannell H, Stief CG, Buchner A, Karl A et al (2022) Retrospective evaluation of the impact of non-oncologic chronic drug therapy on the survival in patients with bladder cancer. Int J Clin Pharm 44(2):339–347. https://doi.org/10.1007/s11096-021-01343-x
doi: 10.1007/s11096-021-01343-x pubmed: 34724148
Samuel SM, Varghese E, Kubatka P, Triggle CR, Büsselberg D et al (2019) Metformin: the answer to cancer in a flower? Current knowledge and future prospects of metformin as an anti-cancer agent in breast cancer. Biomolecules 9(12):846. https://doi.org/10.3390/biom9120846
doi: 10.3390/biom9120846 pubmed: 31835318 pmcid: 6995629
Chen YC, Li H, Wang J (2020) Mechanisms of metformin inhibiting cancer invasion and migration. Am J Transl Res 12(9):4885–4901
pubmed: 33042396 pmcid: 7540116

Auteurs

Ondřej Fiala (O)

Department of Oncology and Radiotherapeutics, Faculty of Medicine and University Hospital Pilsen, Charles University, Alej Svobody 80, 304 60, Pilsen, Czech Republic. fialao@fnplzen.cz.
Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic. fialao@fnplzen.cz.

Sebastiano Buti (S)

Department of Medicine and Surgery, University Hospital of Parma, Parma, Italy.
Medical Oncology Unit, University Hospital of Parma, Parma, Italy.

Hideki Takeshita (H)

Department of Urology, Saitama Medical Center, Saitama Medical University, Saitama, Japan.

Yohei Okada (Y)

Department of Urology, Saitama Medical Center, Saitama Medical University, Saitama, Japan.

Francesco Massari (F)

Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Via Albertoni - 15, Bologna, Italy.

Georgia Anguera Palacios (GA)

Department of Medical Oncology, Institutd' Investigació Biomèdica Sant Pau, Hospital de La Santa Creu I Sant Pau, Barcelona, Spain.

Michele Dionese (M)

Oncology 1 Unit, Department of Oncology, Istituto Oncologico Veneto IOV IRCCS, 35128, Padua, Italy.

Sarah Scagliarini (S)

UOC Di Oncologia, Azienda Ospedaliera Di Rilievo Nazionale Cardarelli Di Napoli, Naples, Italy.

Thomas Büttner (T)

Department of Urology, University Hospital Bonn (UKB), 53127, Bonn, Germany.

Giuseppe Fornarini (G)

IRCCS Ospedale Policlinico San Martino, Genoa, Italy.

Zin W Myint (ZW)

Markey Cancer Center, University of Kentucky, Lexington, KY, 40536-0293, USA.

Luca Galli (L)

Oncology Unit 2, University Hospital of Pisa, 56126, Pisa, Italy.

Vinicius Carrera Souza (VC)

Hospital São Rafael Oncologia D'Or, Salvador, BA, Brazil.
Latin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil.

Renate Pichler (R)

Department of Urology, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria.

Ugo De Giorgi (U)

Department of Medical Oncology, IRCCS Istituto Romagnolo Per Lo Studio Dei Tumori (IRST) "Dino Amadori", Meldola, Italy.

María Natalia Gandur Quiroga (MNG)

Latin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil.
Hospital Angel Roffo, Buenos Aires, CABA, Argentina.

Danielle Gilbert (D)

University of Colorado Cancer Center, Anschutz Medical Campus, Aurora, CO, USA.

Lazar Popovic (L)

Oncology Institute of Vojvodina, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia.

Enrique Grande (E)

Department of Medical Oncology, MD Anderson Cancer Center Madrid, Madrid, Spain.

Giulia Mammone (G)

Department of Radiological, Oncological and Anatomo-Pathological Science, Sapienza University of Rome, Viale Regina Elena 324, 00185, Rome, Italy.

Rossana Berardi (R)

Department of Medical Oncology, Università Politecnica Delle Marche, AOU Ospedali Riuniti Delle Marche, Ancona, Italy.

Simon J Crabb (SJ)

Southampton Experimental Cancer Medicine Centre, University of Southampton, Southampton, UK.

Javier Molina-Cerrillo (J)

Department of Medical Oncology, Hospital Ramón Y Cajal, Madrid, Spain.

Marcelo Freitas (M)

Latin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil.
Centro de Pesquisas Oncológicas - CEPON, Florianópolis, SC, Brazil.

Murilo Luz (M)

Latin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil.
Hospital Erasto Gaertner, Curitiba, PR, Brazil.

Roberto Iacovelli (R)

Oncologia Medica, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.

Fabio Calabrò (F)

Department of Oncology, San Camillo Forlanini Hospital, Rome, Italy.

Deniz Tural (D)

Department of Medical Oncology, Bakirköy Dr. Sadi Konuk Training and Research Hospital, Zuhuratbaba District, Tevfik Saglam St. No: 11, Bakirkoy, Istanbul, Turkey.

Francesco Atzori (F)

Unità Di Oncologia Medica, Azienda Ospedaliero Universitaria Di Cagliari, Cagliari, Italy.

Zsófia Küronya (Z)

Department of Genitourinary Medical Oncology and Clinical Pharmacology, National Institute of Oncology, Budapest, Hungary.

Rita Chiari (R)

UOC Oncologia, Azienda Ospedaliera Ospedali Riuniti Marche Nord, Fano, Italy.

Saul Campos (S)

Latin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil.
Centro Oncologico Estatal "Dr José Luis Barrera Franco" del ISSEMYM, Toluca de Lerdo, Mexico.

Orazio Caffo (O)

Medical Oncology Unit, Santa Chiara Hospital, Trento, Italy.

André P Fay (AP)

Latin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil.
Pontificia Universidade Católica Do Rio Grande Do Sul - PUCRS, Porto Alegre, RS, Brazil.

Jakub Kucharz (J)

Department of Uro-Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.

Paolo Andrea Zucali (PA)

Department of Oncology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.

José Augusto Rinck (JA)

Latin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil.
Hospital AC Camargo, São Paulo, SP, Brazil.

Annalisa Zeppellini (A)

Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy.

Diogo Assed Bastos (DA)

Latin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil.
Department of Oncology, Hospital Sírio-Libanês, São Paulo, SP, Brazil.

Gaetano Aurilio (G)

Medical Oncology Division of Urogenital and Head and Neck Tumours, IEO, European Institute of Oncology IRCCS, Milan, Italy.

Augusto Mota (A)

Latin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil.
Clínica AMO, Salvador, BA, Brazil.

Karine Trindade (K)

Latin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil.
Oncologia D'Or, Fortaleza, CE, Brazil.

Cinzia Ortega (C)

Division of Oncology, Institute for Cancer Research and Treatment, Asl Cn2 Alba-Brà, 12051, Alba-Brà, Italy.

Juan Pablo Sade (JP)

Instituto Alexander Fleming, Buenos Aires, CABA, Argentina.

Mimma Rizzo (M)

Division of Medical Oncology, A.O.U. Consorziale Policlinico Di Bari, Piazza G. Cesare 11, 70124, Bari, Italy.

Nuno Vau (N)

Urologic Oncology, Champalimaud Clinical Center, 1400-038, Lisbon, Portugal.

Patrizia Giannatempo (P)

Dipartimento Di Oncologia Medica, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy.

Allan Barillas (A)

Latin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil.
Clinicas Medicas Especializadas NUCARE, Guatemala City, Guatemala.

Fernando Sabino Marques Monteiro (FSM)

Latin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil.
Oncology and Hematology Department, Hospital Santa Lucia, SHLS 716 Cj. C, Brasília, DF, 70390-700, Brazil.

Breno Dauster (B)

Latin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil.
Hospital Sao Rafael, Salvador, BA, Brazil.

Carlo Cattrini (C)

Department of Medical Oncology, "Maggiore Della Carità" University Hospital, 28100, Novara, Italy.

Lucas Nogueira (L)

Latin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil.
Universidade Federal de Minas Gerais - UFMG, Belo Horizonte, MG, Brazil.

Roni de Carvalho Fernandes (R)

Hospital Santa Casa de Sao Paulo, São Paulo, SP, Brazil.

Emmanuel Seront (E)

Department of Medical Oncology, Centre Hospitalier de Jolimont, Haine Saint Paul, Belgium.

Luís Garcia Aceituno (LG)

Latin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil.
Clinica Medica Especializada en Oncologia Medica, Guatemala City, Guatemala.

Francesco Grillone (F)

SOC Oncologia Medica, Azienda Ospedaliera "Pugliese -Ciaccio", Catanzaro, Italy.

Hernan Javier Cutuli (HJ)

Hospital Sirio Libanes, Buenos Aires, CABA, Argentina.

Mauricio Fernandez (M)

Latin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil.
Fundacion Centro Oncologico de Integracion Regional - COIR, Mendoza, Argentina.

Maria Bassanelli (M)

Medical Oncology, 1-IRCCS Regina Elena National Cancer Institute, Rome, Italy.

Giandomenico Roviello (G)

Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Viale Pieraccini 6, 50139, Florence, Italy.

Halima Abahssain (H)

Medical Oncology Unit, National Institute of Oncology, Medicine and Pharmacy Faculty, Mohammed V University, Rabat, Morocco.

Giuseppe Procopio (G)

Dipartimento Di Oncologia Medica, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy.
Oncologia Medica, Ospedale Maggiore Di Cremona, Cremona, Italy.

Michele Milella (M)

Section of Oncology, Department of Medicine, School of Medicine and Verona University Hospital Trust, University of Verona, Verona, Italy.

Jindrich Kopecky (J)

Department of Clinical Oncology and Radiotherapy, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic.

Angelo Martignetti (A)

UOC Oncologia Medica, Ospedale Dell'alta Val D'Elsa - Usl sud est Toscana Area Senese, Poggibonsi, Italy.

Carlo Messina (C)

Oncology Unit, A.R.N.A.S. Civico, Palermo, Italy.

Manuel Caitano (M)

Latin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil.
Hospital do Câncer Porto Dias - Rede Mater Dei de Saúde, Belém, PA, Brazil.

Eva Inman (E)

Latin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil.
ONCOR Life Medical Center, Saltillo, Mexico.

Ravindran Kanesvaran (R)

National Cancer Centre Singapore, Singapore, Republic of Singapore.

Daniel Herchenhorn (D)

Latin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil.
Instituto D'Or de Ensino E Pesquisa, Rio de Janeiro, RJ, Brazil.

Daniele Santini (D)

Department of Radiological, Oncological and Pathological Sciences, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy.

Ray Manneh (R)

Clinical Oncology, Sociedad de Oncología Y Hematología del Cesar, Valledupar, Colombia.

Renato Bisonni (R)

UOC Oncologia Medica, Ospedale A. Murri, Fermo, Italy.

Roubini Zakopoulou (R)

2nd Propaedeutic Department of Internal Medicine, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece.

Alessandra Mosca (A)

Department of Oncology Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Turin, Italy.

Franco Morelli (F)

Medical Oncology Unit, Gemelli Molise Hospital, Università Cattolica del Sacro Cuore, Campobasso, Italy.

Fernando Maluf (F)

Hospital Beneficencia Portuguesa de São Paulo, São Paulo, SP, Brazil.
Hospital Israelita Albert Einstein, São Paulo, SP, Brazil.

Andrey Soares (A)

Latin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil.
Hospital Israelita Albert Einstein, São Paulo, SP, Brazil.
Centro Paulista de Oncologia/Oncoclinicas, Sao Paulo, Brazil.

Fernando Nunes (F)

Latin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil.
Clinica de Oncologia - Clion, Salvador, BA, Brazil.

Alvaro Pinto (A)

Medical Oncology Department, La Paz University Hospital, Madrid, Spain.

Anca Zgura (A)

Department of Oncology-Radiotherapy, Prof. Dr. Alexandru Trestioreanu Institute of Oncology, University of Medicine and Pharmacy, Bucharest, Romania.

Lorena Incorvaia (L)

Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.

Jawaher Ansari (J)

Medical Oncology, Tawam Hospital, Al Ain, United Arab Emirates.

Ignacio Ortego Zabalza (IO)

Department of Medical Oncology, MD Anderson Cancer Center Madrid, Madrid, Spain.

Johannes Landmesser (J)

Klinik Für Urologie, Ratzeburger Allee 160, 23538, Lübeck, Germany.

Alessandro Rizzo (A)

Struttura Semplice Dipartimentale Di Oncologia Medica Per La Presa in Carico Globale del Paziente Oncologico "Don Tonino Bello", I.R.C.C.S. Istituto Tumori "Giovanni Paolo II", Viale Orazio Flacco 65, 70124, Bari, Italy.

Veronica Mollica (V)

Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Via Albertoni - 15, Bologna, Italy.

Giulia Sorgentoni (G)

Oncology Unit, Macerata Hospital, Via Santa Lucia 2, 62100, Macerata, Italy.

Nicola Battelli (N)

Oncology Unit, Macerata Hospital, Via Santa Lucia 2, 62100, Macerata, Italy.

Camillo Porta (C)

Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy.

Joaquim Bellmunt (J)

Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

Matteo Santoni (M)

Oncology Unit, Macerata Hospital, Via Santa Lucia 2, 62100, Macerata, Italy.

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