Preclinical and early clinical data suggest that the irreversible ErbB family blocker afatinib may be effective in urothelial cancers harbouring ERBB mutations.
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.
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).
An exploratory biomarker analysis suggested that basal-squamous tumours and ERBB2 amplification were associated with superior response to afatinib.
NCT02780687.
British journal of cancer. 2023 Dec 15 [Epub ahead of print]
Albert Font, Begona Mellado, Miguel A Climent, Juan Antonio Virizuela, Stephane Oudard, Javier Puente, Daniel Castellano, Aranzazu González-Del-Alba, Alvaro Pinto, Rafael Morales-Barrera, Alejo Rodriguez-Vida, Pedro L Fernandez, Cristina Teixido, Pedro Jares, Iban Aldecoa, Neil Gibson, Flavio Solca, Shoubhik Mondal, Robert M Lorence, Josep Serra, Francisco X Real
Medical Oncology Department, Institut Català d'Oncologia, Badalona Applied Research Group in Oncology (BARGO), Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain. ., Medical Oncology Department, Hospital Clínic de Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain. ., Medical Oncology Department, Instituto Valenciano de Oncología (IVO), València, Spain., Medical Oncology Service, Hospital Universitario Virgen Macarena, Sevilla, Spain., Medical Oncology Department, Hôpital Européen George Pompidou, University of Paris, Paris, France., Medical Oncology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), CIBERONC, Madrid, Spain., Medical Oncology Department, Hospital Universitario 12 de Octubre, Madrid, Spain., Medical Oncology Department, Hospital Universitario Son Espases, Palma de Mallorca, Spain., Medical Oncology Department, Hospital Universitario La Paz, Instituto de Investigacion Sanitaria Hospital La Paz (IdiPAZ), Madrid, Spain., Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain., Medical Oncology Department, Hospital del Mar, IMIM Research Institute, Barcelona, Spain., Pathology Department, Hospital Germans Trias i Pujol, IGTP, Universitat Autònoma de Barcelona, Barcelona, Spain., Pathology Department, Hospital Clínic Barcelona and Institut d'Investigacions Biomèdiques August Pi i Sunyer, Translational Genomics and Targeted Therapeutics in Solid Tumors, Barcelona, Spain., Molecular Biology CORE and Pathology Department, Hospital Clínic Barcelona, Barcelona, Spain., Pathology Department, Hospital Clínic Barcelona - University of Barcelona and Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain., Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany., Boehringer Ingelheim RCV GmbH & Co. KG, Vienna, Austria., Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, CT, USA., Boehringer Ingelheim España, S.A., Barcelona, Spain., Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain. .