Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Clinical Studies

Phase II trial of afatinib in patients with advanced urothelial carcinoma with genetic alterations in ERBB1-3 (LUX-Bladder 1)

British Journal of Cancer volume 130, pages 434–441 (2024)Cite this article

Subjects

Abstract

Background

Preclinical and early clinical data suggest that the irreversible ErbB family blocker afatinib may be effective in urothelial cancers harbouring ERBB mutations.

Methods

This open-label, phase II, single-arm trial (LUX-Bladder 1, NCT02780687) assessed the efficacy and safety of second-line afatinib 40 mg/d in patients with metastatic urothelial carcinoma with ERBB1-3 alterations. The primary endpoint was 6-month progression-free survival rate (PFS6) (cohort A); other endpoints included ORR, PFS, OS, DCR and safety (cohorts A and B). Cohort A was planned to have two stages: stage 2 enrolment was based on observed antitumour activity.

Results

Thirty-four patients were enroled into cohort A and eight into cohort B. In cohorts A/B, PFS6 was 11.8%/12.5%, ORR was 5.9%/12.5%, DCR was 50.0%/25.0%, median PFS was 9.8/7.8 weeks and median OS was 30.1/29.6 weeks. Three patients (two ERBB2-amplified [cohort A]; one EGFR-amplified [cohort B]) achieved partial responses. Stage 2 for cohort A did not proceed. All patients experienced adverse events (AEs), most commonly (any/grade 3) diarrhoea (76.2%/9.5%). Two patients (4.8%) discontinued due to AEs and one fatal AE was observed (acute coronary syndrome; not considered treatment-related).

Conclusions

An exploratory biomarker analysis suggested that basal-squamous tumours and ERBB2 amplification were associated with superior response to afatinib.

Clinical trial registration

NCT02780687.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Progression-free and overall survival of patients included in the study.

Similar content being viewed by others

Data availability

To ensure independent interpretation of clinical study results and enable authors to fulfil their role and obligations under the ICMJE criteria, Boehringer Ingelheim grants all external authors access to clinical study data pertinent to the development of the publication. In adherence with the Boehringer Ingelheim Policy on Transparency and Publication of Clinical Study Data, scientific and medical researchers can request access to clinical study data when it becomes available on https://vivli.org/, and earliest after publication of the primary manuscript in a peer-reviewed journal, regulatory activities are complete, and other criteria are met. Please visit https://www.mystudywindow.com/msw/datasharing for further information.

References

  1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–49.

    Article  PubMed  Google Scholar 

  2. Pasin E, Josephson DY, Mitra AP, Cote RJ, Stein JP. Superficial bladder cancer: an update on etiology, molecular development, classification, and natural history. Rev Urol. 2008;10:31–43.

    PubMed  PubMed Central  Google Scholar 

  3. Vishnu P, Mathew J, Tan WW. Current therapeutic strategies for invasive and metastatic bladder cancer. Oncol Targets Ther. 2011;4:97–113.

    CAS  Google Scholar 

  4. von der Maase H, Hansen SW, Roberts JT, Dogliotti L, Oliver T, Moore MJ, et al. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol. 2000;18:3068–77.

    Article  PubMed  Google Scholar 

  5. Galsky MD, Chen GJ, Oh WK, Bellmunt J, Roth BJ, Petrioli R, et al. Comparative effectiveness of cisplatin-based and carboplatin-based chemotherapy for treatment of advanced urothelial carcinoma. Ann Oncol. 2012;23:406–10.

    Article  CAS  PubMed  Google Scholar 

  6. Balar AV, Castellano D, O’Donnell PH, Grivas P, Vuky J, Powles T, et al. First-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer (KEYNOTE-052): a multicentre, single-arm, phase 2 study. Lancet Oncol. 2017;18:1483–92.

    Article  CAS  PubMed  Google Scholar 

  7. Balar AV, Galsky MD, Rosenberg JE, Powles T, Petrylak DP, Bellmunt J, et al. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet. 2017;389:67–76.

    Article  CAS  PubMed  Google Scholar 

  8. von der Maase H, Sengelov L, Roberts JT, Ricci S, Dogliotti L, Oliver T, et al. Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol. 2005;23:4602–8.

    Article  PubMed  Google Scholar 

  9. Powles T, Park SH, Voog E, Caserta C, Valderrama BP, Gurney H, et al. Avelumab maintenance therapy for advanced or metastatic urothelial carcinoma. N Engl J Med. 2020;383:1218–30.

    Article  CAS  PubMed  Google Scholar 

  10. Bellmunt J, Theodore C, Demkov T, Komyakov B, Sengelov L, Daugaard G, et al. Phase III trial of vinflunine plus best supportive care compared with best supportive care alone after a platinum-containing regimen in patients with advanced transitional cell carcinoma of the urothelial tract. J Clin Oncol. 2009;27:4454–61.

    Article  CAS  PubMed  Google Scholar 

  11. McCaffrey JA, Hilton S, Mazumdar M, Sadan S, Kelly WK, Scher HI, et al. Phase II trial of docetaxel in patients with advanced or metastatic transitional-cell carcinoma. J Clin Oncol. 1997;15:1853–7.

    Article  CAS  PubMed  Google Scholar 

  12. Vaughn DJ, Broome CM, Hussain M, Gutheil JC, Markowitz AB. Phase II trial of weekly paclitaxel in patients with previously treated advanced urothelial cancer. J Clin Oncol. 2002;20:937–40.

    Article  CAS  PubMed  Google Scholar 

  13. Bellmunt J, Powles T, Vogelzang NJ. A review on the evolution of PD-1/PD-L1 immunotherapy for bladder cancer: the future is now. Cancer Treat Rev. 2017;54:58–67.

    Article  CAS  PubMed  Google Scholar 

  14. Loriot Y, Necchi A, Park SH, Garcia-Donas J, Huddart R, Burgess E, et al. Erdafitinib in locally advanced or metastatic urothelial carcinoma. N Engl J Med. 2019;381:338–48.

    Article  CAS  PubMed  Google Scholar 

  15. Rosenberg J, Sridhar SS, Zhang J, Smith D, Ruether D, Flaig TW, et al. EV-101: a phase I study of single-agent enfortumab vedotin in patients with nectin-4-positive solid tumors, including metastatic urothelial carcinoma. J Clin Oncol. 2020;38:1041–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Powles T, Rosenberg JE, Sonpavde GP, Loriot Y, Duran I, Lee JL, et al. Enfortumab vedotin in previously treated advanced urothelial carcinoma. N Engl J Med. 2021;384:1125–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Lawrence MS, Stojanov P, Polak P, Kryukov GV, Cibulskis K, Sivachenko A, et al. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature. 2013;499:214–8.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  18. Robertson AG, Kim J, Al-Ahmadie H, Bellmunt J, Guo G, Cherniack AD, et al. Comprehensive molecular characterization of muscle-invasive bladder cancer. Cell. 2017;171:540–56.e25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Koshkin VS, O’Donnell P, Yu EY, Grivas P. Systematic review: targeting HER2 in bladder cancer. Bladder Cancer. 2019;5:1–12.

    Article  Google Scholar 

  20. Oudard S, Culine S, Vano Y, Goldwasser F, Theodore C, Nguyen T, et al. Multicentre randomised phase II trial of gemcitabine+platinum, with or without trastuzumab, in advanced or metastatic urothelial carcinoma overexpressing Her2. Eur J Cancer. 2015;51:45–54.

    Article  CAS  PubMed  Google Scholar 

  21. Powles T, Huddart RA, Elliott T, Sarker SJ, Ackerman C, Jones R, et al. Phase III, double-blind, randomized trial that compared maintenance lapatinib versus placebo after first-line chemotherapy in patients with human epidermal growth factor receptor 1/2-positive metastatic bladder cancer. J Clin Oncol. 2017;35:48–55.

    Article  CAS  PubMed  Google Scholar 

  22. Sheng X, Yan X, Wang L, Shi Y, Yao X, Luo H, et al. Open-label, multicenter, phase II study of RC48-ADC, a HER2-targeting antibody-drug conjugate, in patients with locally advanced or metastatic urothelial carcinoma. Clin Cancer Res. 2021;27:43–51.

    Article  CAS  PubMed  Google Scholar 

  23. Mooso BA, Vinall RL, Mudryj M, Yap SA, deVere White RW, Ghosh PM. The role of EGFR family inhibitors in muscle invasive bladder cancer: a review of clinical data and molecular evidence. J Urol. 2015;193:19–29.

    Article  CAS  PubMed  Google Scholar 

  24. Chow NH, Chan SH, Tzai TS, Ho CL, Liu HS. Expression profiles of ErbB family receptors and prognosis in primary transitional cell carcinoma of the urinary bladder. Clin Cancer Res. 2001;7:1957–62.

    CAS  PubMed  Google Scholar 

  25. van Kessel KE, Zuiverloon TC, Alberts AR, Boormans JL, Zwarthoff EC. Targeted therapies in bladder cancer: an overview of in vivo research. Nat Rev Urol. 2015;12:681–94.

    Article  PubMed  Google Scholar 

  26. Iyer G, Al-Ahmadie H, Schultz N, Hanrahan AJ, Ostrovnaya I, Balar AV, et al. Prevalence and co-occurrence of actionable genomic alterations in high-grade bladder cancer. J Clin Oncol. 2013;31:3133–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Oh DY, Bang YJ. HER2-targeted therapies - a role beyond breast cancer. Nat Rev Clin Oncol. 2020;17:33–48.

    Article  CAS  PubMed  Google Scholar 

  28. Neal DE, Marsh C, Bennett MK, Abel PD, Hall RR, Sainsbury JR, et al. Epidermal-growth-factor receptors in human bladder cancer: comparison of invasive and superficial tumours. Lancet. 1985;1:366–8.

    Article  CAS  PubMed  Google Scholar 

  29. Kamoun A, de Reynies A, Allory Y, Sjodahl G, Robertson AG, Seiler R, et al. A consensus molecular classification of muscle-invasive bladder cancer. Eur Urol. 2020;77:420–33.

    Article  PubMed  Google Scholar 

  30. Chow NH, Liu HS, Lee EI, Chang CJ, Chan SH, Cheng HL, et al. Significance of urinary epidermal growth factor and its receptor expression in human bladder cancer. Anticancer Res. 1997;17:1293–6.

    CAS  PubMed  Google Scholar 

  31. Neal DE, Sharples L, Smith K, Fennelly J, Hall RR, Harris AL. The epidermal growth factor receptor and the prognosis of bladder cancer. Cancer. 1990;65:1619–25.

    Article  CAS  PubMed  Google Scholar 

  32. Nguyen PL, Swanson PE, Jaszcz W, Aeppli DM, Zhang G, Singleton TP, et al. Expression of epidermal growth factor receptor in invasive transitional cell carcinoma of the urinary bladder. A multivariate survival analysis. Am J Clin Pathol. 1994;101:166–76.

    Article  CAS  PubMed  Google Scholar 

  33. Solca F, Dahl G, Zoephel A, Bader G, Sanderson M, Klein C, et al. Target binding properties and cellular activity of afatinib (BIBW 2992), an irreversible ErbB family blocker. J Pharm Exp Ther. 2012;343:342–50.

    Article  CAS  Google Scholar 

  34. Nagano M, Kohsaka S, Ueno T, Kojima S, Saka K, Iwase H, et al. High-throughput functional evaluation of variants of unknown significance in ERBB2. Clin Cancer Res. 2018;24:5112–22.

    Article  CAS  PubMed  Google Scholar 

  35. Perera SA, Li D, Shimamura T, Raso MG, Ji H, Chen L, et al. HER2YVMA drives rapid development of adenosquamous lung tumors in mice that are sensitive to BIBW2992 and rapamycin combination therapy. Proc Natl Acad Sci USA. 2009;106:474–9.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  36. Yamamoto H, Toyooka S, Ninomiya T, Matsumoto S, Kanai M, Tomida S, et al. Therapeutic potential of afatinib for cancers with ERBB2 (HER2) transmembrane domain mutations G660D and V659E. Oncologist. 2018;23:150–4.

    Article  CAS  PubMed  Google Scholar 

  37. Tamura S, Wang Y, Veeneman B, Hovelson D, Bankhead A 3rd, Broses LJ, et al. Molecular correlates of in vitro responses to dacomitinib and afatinib in bladder cancer. Bladder Cancer. 2018;4:77–90.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Choudhury NJ, Campanile A, Antic T, Yap KL, Fitzpatrick CA, Wade JL 3rd, et al. Afatinib activity in platinum-refractory metastatic urothelial carcinoma in patients with ERBB alterations. J Clin Oncol. 2016;34:2165–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Agarwal N, Bellmunt J, Maughan BL, Boucher KM, Choueiri TK, Qu AQ, et al. Six-month progression-free survival as the primary endpoint to evaluate the activity of new agents as second-line therapy for advanced urothelial carcinoma. Clin Genitourin Cancer. 2014;12:130–7.

    Article  PubMed  Google Scholar 

  40. Rebouissou S, Bernard-Pierrot I, de Reynies A, Lepage ML, Krucker C, Chapeaublanc E, et al. EGFR as a potential therapeutic target for a subset of muscle-invasive bladder cancers presenting a basal-like phenotype. Sci Transl Med. 2014;6:244ra91.

    Article  PubMed  Google Scholar 

  41. Hochmair M. Medical treatment options for patients with epidermal growth factor receptor mutation-positive non-small cell lung cancer suffering from brain metastases and/or leptomeningeal disease. Target Oncol. 2018;13:269–85.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Mari A, D’Andrea D, Abufaraj M, Foerster B, Kimura S, Shariat SF. Genetic determinants for chemo- and radiotherapy resistance in bladder cancer. Transl Androl Urol. 2017;6:1081–9.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Lattanzi M, Rosenberg JE. The emerging role of antibody-drug conjugates in urothelial carcinoma. Expert Rev Anticancer Ther. 2020;20:551–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Hussain SA, Lester JF, Jackson R, Gornall M, Qureshi M, Elliott A, et al. Addition of nintedanib or placebo to neoadjuvant gemcitabine and cisplatin in locally advanced muscle-invasive bladder cancer (NEOBLADE): a double-blind, randomised, phase 2 trial. Lancet Oncol. 2022;23:650–8.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank the patients, their families, and all the investigators who participated in these studies. The authors gratefully recognise the contributions of staff from the August Pi i Sunyer Biomedical Research Institute (IDIBAPS) in supporting the centralised screening of patients, and also staff at the Department of Pathology, Hospital Clinic Barcelona, for their work characterising PD-L1 status. The authors also acknowledge Karin Bosch, Regina Ruzika, Susanne Schmittner and Johanna Woertl for their excellent technical contributions regarding preclinical data. The authors were fully responsible for all content and editorial decisions, were involved at all stages of manuscript development, and have approved the final version. The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE). Boehringer Ingelheim was given the opportunity to review the manuscript for medical and scientific accuracy as well as intellectual property considerations.

Funding

The conduct of this research, study design, data collection and analysis were financially supported by Boehringer Ingelheim. The authors did not receive payment related to the development of this manuscript. Medical writing assistance, funded by Boehringer Ingelheim, was provided by Sharmin Bovill, Ph.D., and Jim Sinclair, Ph.D., of Ashfield MedComms, an Inizio Company, during the preparation of this manuscript.

Author information

Author notes

  1. These authors contributed equally: Albert Font, Begona Mellado.

Authors and Affiliations

  1. Medical Oncology Department, Institut Català d’Oncologia, Badalona Applied Research Group in Oncology (BARGO), Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain

    Albert Font

  2. Medical Oncology Department, Hospital Clínic de Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain

    Begona Mellado

  3. Medical Oncology Department, Instituto Valenciano de Oncología (IVO), València, Spain

    Miguel A. Climent

  4. Medical Oncology Service, Hospital Universitario Virgen Macarena, Sevilla, Spain

    Juan Antonio Virizuela

  5. Medical Oncology Department, Hôpital Européen George Pompidou, University of Paris, Paris, France

    Stephane Oudard

  6. Medical Oncology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), CIBERONC, Madrid, Spain

    Javier Puente

  7. Medical Oncology Department, Hospital Universitario 12 de Octubre, Madrid, Spain

    Daniel Castellano

  8. Medical Oncology Department, Hospital Universitario Son Espases, Palma de Mallorca, Spain

    Aranzazu González-del-Alba

  9. Medical Oncology Department, Hospital Universitario La Paz, Instituto de Investigacion Sanitaria Hospital La Paz (IdiPAZ), Madrid, Spain

    Alvaro Pinto

  10. Vall d’Hebron Institute of Oncology, Vall d’Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain

    Rafael Morales-Barrera

  11. Medical Oncology Department, Hospital del Mar, IMIM Research Institute, Barcelona, Spain

    Alejo Rodriguez-Vida

  12. Pathology Department, Hospital Germans Trias i Pujol, IGTP, Universitat Autònoma de Barcelona, Barcelona, Spain

    Pedro L. Fernandez

  13. Pathology Department, Hospital Clínic Barcelona and Institut d’Investigacions Biomèdiques August Pi i Sunyer, Translational Genomics and Targeted Therapeutics in Solid Tumors, Barcelona, Spain

    Cristina Teixido

  14. Molecular Biology CORE and Pathology Department, Hospital Clínic Barcelona, Barcelona, Spain

    Pedro Jares

  15. Pathology Department, Hospital Clínic Barcelona - University of Barcelona and Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain

    Iban Aldecoa

  16. Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany

    Neil Gibson

  17. Boehringer Ingelheim RCV GmbH & Co. KG, Vienna, Austria

    Flavio Solca

  18. Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, CT, USA

    Shoubhik Mondal & Robert M. Lorence

  19. Boehringer Ingelheim España, S.A., Barcelona, Spain

    Josep Serra

  20. Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain

    Francisco X. Real

  21. CIBERONC, Madrid, Spain

    Francisco X. Real

  22. Universitat Pompeu Fabra, Barcelona, Spain

    Francisco X. Real

Authors
  1. Albert Font
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Begona Mellado
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Miguel A. Climent
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Juan Antonio Virizuela
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Stephane Oudard
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Javier Puente
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Daniel Castellano
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Aranzazu González-del-Alba
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Alvaro Pinto
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Rafael Morales-Barrera
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Alejo Rodriguez-Vida
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Pedro L. Fernandez
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Cristina Teixido
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Pedro Jares
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Iban Aldecoa
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Neil Gibson
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Flavio Solca
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Shoubhik Mondal
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Robert M. Lorence
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Josep Serra
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Francisco X. Real
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

AF: Conceptualisation, Methodology, Resources, Supervision, Writing—Review & Editing. BM: Conceptualisation, Methodology, Investigation, Writing—Original Draft, Writing—Review & Editing. MAC: Investigation, Visualisation, Writing—Review & Editing. JAV: Conceptualisation, Resources, Data Curation, Writing—Review & Editing. SO: Visualisation, Writing—Review & Editing. JP: Conceptualisation, Validation, Formal analysis, Investigation, Resources, Data Curation, Visualisation, Supervision, Writing—Original Draft, Writing—Review & Editing. DC: Conceptualisation, Investigation, Supervision, Writing—Review & Editing. AG-del-A: Investigation, Validation, Resources, Data Curation, Writing—Review & Editing. AP: Investigation, Resources, Data Curation, Writing—Review & Editing. RM-B: Investigation, Validation, Resources, Writing—Review & Editing. AR-V: Conceptualisation, Methodology, Investigation, Validation, Visualisation, Supervision, Writing—Original Draft, Writing—Review & Editing. PLF: Methodology, Investigation, Writing—Review & Editing. CT: Methodology, Validation, Investigation, Data Curation, Writing—Review & Editing. PJ: Methodology, Validation, Formal Analysis, Investigation, Writing—Review & Editing. IA: Investigation, Writing—Review & Editing. NG: Conceptualisation, Methodology, Investigation, Supervision, Writing—Review & Editing. FS: Conceptualisation, Investigation, Visualisation, Supervision, Writing—Original Draft, Writing—Review & Editing. SM: Formal Analysis, Writing—Review & Editing. RML: Supervision, Project Administration, Writing—Original Draft, Writing—Review & Editing. JS: Supervision, Project Administration, Writing—Review & Editing. FXR: Conceptualisation, Methodology, Clinical Trial Design, Writing—Original Draft, Writing—Review & Editing.

Corresponding authors

Correspondence to Albert Font, Begona Mellado or Francisco X. Real.

Ethics declarations

Competing interests

AF has served for an advisory council or committee for Janssen, Astellas, Sanofi, Roche, EUSA, AstraZeneca; and received grants or funds from AstraZeneca, Pierre Fabre. BM has received grants or funds (recipient: herself) from Janssen, Roche, Astellas, Sanofi, Bayer; speaker bureau and travel accommodation fees from Pfizer, Ipsen, Janssen, Roche; and speaker bureau fees from Astellas, Sanofi, Bristol-Myers Squibb, Bayer. MAC has received honoraria for speaker engagements, advisory roles and continuous medical education from Janssen, AstraZeneca, Astellas, Merck Sharp & Dohme, Pfizer, EUSA MSD, Roche, Ipsen, Sanofi, Merck, Bristol-Myers Squibb. SO has received honoraria, consulting fees and any other potential financial relationship from Bayer, Pfizer, Sanofi, Bristol-Myers Squibb, Merck, Novartis, Astellas, Janssen, Ipsen, AstraZeneca; and grants or funds from Bayer, Pfizer, Sanofi, Bristol-Myers Squibb, Janssen, Ipsen, AstraZeneca. JP has received honoraria for speaker engagements, advisory roles or continuous medical education from Astellas, AstraZeneca, Janssen, Merck Sharp & Dohme, Bayer, Pfizer, Eisai, Ipsen, Sanofi, Roche, Bristol-Myers Squibb, Pierre Fabre, Merck; research funding from Astellas, Pfizer; and consultancy fees from Astellas and Roche. DC has received honoraria from Pfizer, Bristol-Myers Squibb, Roche, Janssen, Astellas, Novartis, Exelisis, Ipsen, Bayer, Lilly, Eisai, Merck Sharp & Dohme; and grants or funds from Janssen, Astellas. AG-d-A has received research funding from Astellas; travel grants from Astellas, Jansen, Sanofi, Bristol-Myers Squibb, Roche, Pfizer, Ipsen; and honoraria for speaker engagements, advisory boards and continuous medical education from Janssen, Astellas, Sanofi, Bayer, Roche, Ipsen, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, EUSA Pharma, Eisai, AstraZeneca. AP has received consulting fees from Pfizer, Bristol-Myers Squibb, Ipsen, Astellas, Janssen, Merck Sharp & Dohme, Merck, Clovis, Roche, Bayer, Sanofi, Novartis; and grants or funds from Pfizer, Bristol-Myers Squibb. RM-B (all unrelated in the last 3 years) has received consulting or advisory and/or speakers bureau fees from Sanofi Aventis, AstraZeneca, Merck Sharp & Dohme, Astellas, Bristol-Myers Squibb; and travel and accommodations expenses from Roche, Sanofi Aventis, Astellas, Janssen, Merck Sharp & Dohme, Bayer, Pfizer. PLF has received non-personal fees from collaborations with Diaceutics. CT has received research funding from Novartis; consulting or advisory and/or speakers bureau fees from Diaceutics, Pfizer, Novartis, AstraZeneca, Takeda, Roche, Bristol-Myers Squibb, Merck Sharp & Dohme. IA has received travel grants from Sysmex. NG, FS, SM, RML and JS report employment with Boehringer Ingelheim. RML also declares being a paid consultant to Boehringer Ingelheim. All the other authors declare no potential conflict of interest.

Ethics approval and consent to participate

The study was approved by the institutional review boards of the participating centres before trial initiation. Informed consent was obtained from each participant included in the study. All procedures performed in the study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Font, A., Mellado, B., Climent, M.A. et al. Phase II trial of afatinib in patients with advanced urothelial carcinoma with genetic alterations in ERBB1-3 (LUX-Bladder 1). Br J Cancer 130, 434–441 (2024). https://doi.org/10.1038/s41416-023-02513-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41416-023-02513-6

Search

Advanced search

Quick links