PMID- 38102226
OWN - NLM
STAT- MEDLINE
DCOM- 20240215
LR  - 20240305
IS  - 1532-1827 (Electronic)
IS  - 0007-0920 (Print)
IS  - 0007-0920 (Linking)
VI  - 130
IP  - 3
DP  - 2024 Feb
TI  - Phase II trial of afatinib in patients with advanced urothelial carcinoma with 
      genetic alterations in ERBB1-3 (LUX-Bladder 1).
PG  - 434-441
LID - 10.1038/s41416-023-02513-6 [doi]
AB  - 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.
CI  - (c) 2023. The Author(s), under exclusive licence to Springer Nature Limited.
FAU - Font, Albert
AU  - Font A
AUID- ORCID: 0000-0003-3908-1111
AD  - Medical Oncology Department, Institut Catala d'Oncologia, Badalona Applied 
      Research Group in Oncology (BARGO), Hospital Universitari Germans Trias i Pujol, 
      Badalona, Barcelona, Spain. afont@iconcologia.net.
FAU - Mellado, Begona
AU  - Mellado B
AD  - Medical Oncology Department, Hospital Clinic de Barcelona, IDIBAPS, University of 
      Barcelona, Barcelona, Spain. bmellado@clinic.cat.
FAU - Climent, Miguel A
AU  - Climent MA
AD  - Medical Oncology Department, Instituto Valenciano de Oncologia (IVO), Valencia, 
      Spain.
FAU - Virizuela, Juan Antonio
AU  - Virizuela JA
AD  - Medical Oncology Service, Hospital Universitario Virgen Macarena, Sevilla, Spain.
FAU - Oudard, Stephane
AU  - Oudard S
AD  - Medical Oncology Department, Hopital Europeen George Pompidou, University of 
      Paris, Paris, France.
FAU - Puente, Javier
AU  - Puente J
AD  - Medical Oncology Department, Hospital Clinico San Carlos, Instituto de 
      Investigacion Sanitaria del Hospital Clinico San Carlos (IdISSC), CIBERONC, 
      Madrid, Spain.
FAU - Castellano, Daniel
AU  - Castellano D
AD  - Medical Oncology Department, Hospital Universitario 12 de Octubre, Madrid, Spain.
FAU - Gonzalez-Del-Alba, Aranzazu
AU  - Gonzalez-Del-Alba A
AD  - Medical Oncology Department, Hospital Universitario Son Espases, Palma de 
      Mallorca, Spain.
FAU - Pinto, Alvaro
AU  - Pinto A
AD  - Medical Oncology Department, Hospital Universitario La Paz, Instituto de 
      Investigacion Sanitaria Hospital La Paz (IdiPAZ), Madrid, Spain.
FAU - Morales-Barrera, Rafael
AU  - Morales-Barrera R
AD  - Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, 
      Universitat Autonoma de Barcelona, Barcelona, Spain.
FAU - Rodriguez-Vida, Alejo
AU  - Rodriguez-Vida A
AD  - Medical Oncology Department, Hospital del Mar, IMIM Research Institute, 
      Barcelona, Spain.
FAU - Fernandez, Pedro L
AU  - Fernandez PL
AD  - Pathology Department, Hospital Germans Trias i Pujol, IGTP, Universitat Autonoma 
      de Barcelona, Barcelona, Spain.
FAU - Teixido, Cristina
AU  - Teixido C
AD  - Pathology Department, Hospital Clinic Barcelona and Institut d'Investigacions 
      Biomediques August Pi i Sunyer, Translational Genomics and Targeted Therapeutics 
      in Solid Tumors, Barcelona, Spain.
FAU - Jares, Pedro
AU  - Jares P
AD  - Molecular Biology CORE and Pathology Department, Hospital Clinic Barcelona, 
      Barcelona, Spain.
FAU - Aldecoa, Iban
AU  - Aldecoa I
AD  - Pathology Department, Hospital Clinic Barcelona - University of Barcelona and 
      Institut d'Investigacions Biomediques August Pi i Sunyer, Barcelona, Spain.
FAU - Gibson, Neil
AU  - Gibson N
AD  - Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
FAU - Solca, Flavio
AU  - Solca F
AD  - Boehringer Ingelheim RCV GmbH & Co. KG, Vienna, Austria.
FAU - Mondal, Shoubhik
AU  - Mondal S
AD  - Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, CT, USA.
FAU - Lorence, Robert M
AU  - Lorence RM
AD  - Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, CT, USA.
FAU - Serra, Josep
AU  - Serra J
AD  - Boehringer Ingelheim Espana, S.A., Barcelona, Spain.
FAU - Real, Francisco X
AU  - Real FX
AUID- ORCID: 0000-0001-9501-498X
AD  - Centro Nacional de Investigaciones Oncologicas (CNIO), Madrid, Spain. 
      freal@cnio.es.
AD  - CIBERONC, Madrid, Spain. freal@cnio.es.
AD  - Universitat Pompeu Fabra, Barcelona, Spain. freal@cnio.es.
LA  - eng
SI  - ClinicalTrials.gov/NCT02780687
SI  - ClinicalTrials.gov/NCT02780687
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20231215
PL  - England
TA  - Br J Cancer
JT  - British journal of cancer
JID - 0370635
RN  - 41UD74L59M (Afatinib)
SB  - IM
MH  - Humans
MH  - *Afatinib/adverse effects
MH  - *Carcinoma, Transitional Cell/drug therapy/genetics
MH  - Mutation
MH  - Urinary Bladder/pathology
MH  - *Urinary Bladder Neoplasms/drug therapy/genetics
PMC - PMC10844502
COIS- 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.
EDAT- 2023/12/16 11:42
MHDA- 2024/02/07 06:43
PMCR- 2024/12/15
CRDT- 2023/12/15 23:32
PHST- 2022/11/02 00:00 [received]
PHST- 2023/11/21 00:00 [accepted]
PHST- 2023/10/31 00:00 [revised]
PHST- 2024/12/15 00:00 [pmc-release]
PHST- 2024/02/07 06:43 [medline]
PHST- 2023/12/16 11:42 [pubmed]
PHST- 2023/12/15 23:32 [entrez]
AID - 10.1038/s41416-023-02513-6 [pii]
AID - 2513 [pii]
AID - 10.1038/s41416-023-02513-6 [doi]
PST - ppublish
SO  - Br J Cancer. 2024 Feb;130(3):434-441. doi: 10.1038/s41416-023-02513-6. Epub 2023 
      Dec 15.