Opening of a phase Ib/II study to investigate the safety and efficacy of Afatinib in patients with Fanconi anemia and unresectable locally advanced or metastatic head and neck squamous cell carcinoma

Individuals diagnosed with Fanconi anemia (FA) present an incidence of 500- to 700-fold higher to develop head and neck squamous carcinomas (HNSCCs) compared to the general population. Effective anticancer treatments for FA-HNSCCs are missing. Several studies demonstrated that FA-HNSCCs overexpress...

Full description

Bibliographic Details
Authors: Anguera, Georgia|||0000-0002-6060-1110, Gallego Rubio, Oscar|||0000-0001-5665-0967, Llobet, Mireia, Berga, Núria|||0009-0002-1488-8998, Moreno Martinez, Maria Estela|||0000-0001-6752-873X, Leon, Xavier, Kratz, Christian, Garcia-Escudero, Ramon|||0000-0001-5640-6542, Minguillón Pedreño, Jordi|||0000-0003-2124-8294, Surralles, Jordi|||0000-0002-4041-7519
Format: article
Publication Date:2025
Country:España
Institution:Universitat Autònoma de Barcelona
Repository:Dipòsit Digital de Documents de la UAB
Language:English
OAI Identifier:oai:ddd.uab.cat:319822
Online Access:https://ddd.uab.cat/record/319822
https://dx.doi.org/urn:doi:10.1186/s12885-025-14619-6
Access Level:Open access
Keyword:Fanconi anemia
Head and neck squamous cell carcinoma
EGFR inhibitors
Afatinib
id ES_2b8f0b828d48a9775fc12a5524ea101e
oai_identifier_str oai:ddd.uab.cat:319822
network_acronym_str ES
network_name_str España
repository_id_str
spelling Opening of a phase Ib/II study to investigate the safety and efficacy of Afatinib in patients with Fanconi anemia and unresectable locally advanced or metastatic head and neck squamous cell carcinomaAnguera, Georgia|||0000-0002-6060-1110Gallego Rubio, Oscar|||0000-0001-5665-0967Llobet, MireiaBerga, Núria|||0009-0002-1488-8998Moreno Martinez, Maria Estela|||0000-0001-6752-873XLeon, XavierKratz, ChristianGarcia-Escudero, Ramon|||0000-0001-5640-6542Minguillón Pedreño, Jordi|||0000-0003-2124-8294Surralles, Jordi|||0000-0002-4041-7519Fanconi anemiaHead and neck squamous cell carcinomaEGFR inhibitorsAfatinibIndividuals diagnosed with Fanconi anemia (FA) present an incidence of 500- to 700-fold higher to develop head and neck squamous carcinomas (HNSCCs) compared to the general population. Effective anticancer treatments for FA-HNSCCs are missing. Several studies demonstrated that FA-HNSCCs overexpress the epithelial growth factor receptor (EGFR) and their viability is highly dependent on this pathway, as FA-HNSCCs cells are highly sensitive to EGFR inhibitors such as afatinib in preclinical models, which led to an orphan drug designation by EMA in 2018. The AFAN trial is a phase Ib/II, single arm, non-randomized, open-label, multicenter study to determine whether afatinib is effective and safe in patients with FA and advanced / metastatic HNSCC. Patients could be treatment-naïve or progressed to a previous systemic treatment with immunotherapy, chemotherapy or cetuximab. Afatinib will be administered orally at a starting dose of 20 mg /day (weeks 1-2), escalating to 30 mg / day at weeks 3-4 and to 40 mg / day thereafter provided no adverse events occur. Treatment will be maintained until disease progression / secondary primary tumor, loss to follow-up, unacceptable toxicity, patient withdrawal or death. Dose reductions and delays will be allowed. All patients will undergo periodic tumor assessments by CT or MRI scan every 12 weeks (3 months) from the start of the study treatment until progression / SPT or patient withdrawal. The primary endpoint is objective response rate (ORR) after 9 months of study treatment initiation according to RECIST V1.1. Secondary endpoints include disease control rate, duration of response, disease-free survival, overall survival, safety, patient reported outcomes and ancillary studies. The expected sample size is 25 patients calculated using a Simon II stage design (α = 0.1; β = 80%), taking as null hypothesis a 9-month ORR of 20% and an alternative ORR of 40%. The AFAN trial will investigate if afatinib is an effective treatment in FA patients with unresectable and / or metastatic locoregionally advanced squamous cell carcinoma of the oral cavity, oropharynx or hypopharynx or larynx. 22025-01-0120252025-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/319822https://dx.doi.org/urn:doi:10.1186/s12885-025-14619-6reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengInstituto de Salud Carlos III https://doi.org/10.13039/501100004587 ICI22/00076open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:3198222026-06-06T12:50:31Z
dc.title.none.fl_str_mv Opening of a phase Ib/II study to investigate the safety and efficacy of Afatinib in patients with Fanconi anemia and unresectable locally advanced or metastatic head and neck squamous cell carcinoma
title Opening of a phase Ib/II study to investigate the safety and efficacy of Afatinib in patients with Fanconi anemia and unresectable locally advanced or metastatic head and neck squamous cell carcinoma
spellingShingle Opening of a phase Ib/II study to investigate the safety and efficacy of Afatinib in patients with Fanconi anemia and unresectable locally advanced or metastatic head and neck squamous cell carcinoma
Anguera, Georgia|||0000-0002-6060-1110
Fanconi anemia
Head and neck squamous cell carcinoma
EGFR inhibitors
Afatinib
title_short Opening of a phase Ib/II study to investigate the safety and efficacy of Afatinib in patients with Fanconi anemia and unresectable locally advanced or metastatic head and neck squamous cell carcinoma
title_full Opening of a phase Ib/II study to investigate the safety and efficacy of Afatinib in patients with Fanconi anemia and unresectable locally advanced or metastatic head and neck squamous cell carcinoma
title_fullStr Opening of a phase Ib/II study to investigate the safety and efficacy of Afatinib in patients with Fanconi anemia and unresectable locally advanced or metastatic head and neck squamous cell carcinoma
title_full_unstemmed Opening of a phase Ib/II study to investigate the safety and efficacy of Afatinib in patients with Fanconi anemia and unresectable locally advanced or metastatic head and neck squamous cell carcinoma
title_sort Opening of a phase Ib/II study to investigate the safety and efficacy of Afatinib in patients with Fanconi anemia and unresectable locally advanced or metastatic head and neck squamous cell carcinoma
dc.creator.none.fl_str_mv Anguera, Georgia|||0000-0002-6060-1110
Gallego Rubio, Oscar|||0000-0001-5665-0967
Llobet, Mireia
Berga, Núria|||0009-0002-1488-8998
Moreno Martinez, Maria Estela|||0000-0001-6752-873X
Leon, Xavier
Kratz, Christian
Garcia-Escudero, Ramon|||0000-0001-5640-6542
Minguillón Pedreño, Jordi|||0000-0003-2124-8294
Surralles, Jordi|||0000-0002-4041-7519
author Anguera, Georgia|||0000-0002-6060-1110
author_facet Anguera, Georgia|||0000-0002-6060-1110
Gallego Rubio, Oscar|||0000-0001-5665-0967
Llobet, Mireia
Berga, Núria|||0009-0002-1488-8998
Moreno Martinez, Maria Estela|||0000-0001-6752-873X
Leon, Xavier
Kratz, Christian
Garcia-Escudero, Ramon|||0000-0001-5640-6542
Minguillón Pedreño, Jordi|||0000-0003-2124-8294
Surralles, Jordi|||0000-0002-4041-7519
author_role author
author2 Gallego Rubio, Oscar|||0000-0001-5665-0967
Llobet, Mireia
Berga, Núria|||0009-0002-1488-8998
Moreno Martinez, Maria Estela|||0000-0001-6752-873X
Leon, Xavier
Kratz, Christian
Garcia-Escudero, Ramon|||0000-0001-5640-6542
Minguillón Pedreño, Jordi|||0000-0003-2124-8294
Surralles, Jordi|||0000-0002-4041-7519
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Fanconi anemia
Head and neck squamous cell carcinoma
EGFR inhibitors
Afatinib
topic Fanconi anemia
Head and neck squamous cell carcinoma
EGFR inhibitors
Afatinib
description Individuals diagnosed with Fanconi anemia (FA) present an incidence of 500- to 700-fold higher to develop head and neck squamous carcinomas (HNSCCs) compared to the general population. Effective anticancer treatments for FA-HNSCCs are missing. Several studies demonstrated that FA-HNSCCs overexpress the epithelial growth factor receptor (EGFR) and their viability is highly dependent on this pathway, as FA-HNSCCs cells are highly sensitive to EGFR inhibitors such as afatinib in preclinical models, which led to an orphan drug designation by EMA in 2018. The AFAN trial is a phase Ib/II, single arm, non-randomized, open-label, multicenter study to determine whether afatinib is effective and safe in patients with FA and advanced / metastatic HNSCC. Patients could be treatment-naïve or progressed to a previous systemic treatment with immunotherapy, chemotherapy or cetuximab. Afatinib will be administered orally at a starting dose of 20 mg /day (weeks 1-2), escalating to 30 mg / day at weeks 3-4 and to 40 mg / day thereafter provided no adverse events occur. Treatment will be maintained until disease progression / secondary primary tumor, loss to follow-up, unacceptable toxicity, patient withdrawal or death. Dose reductions and delays will be allowed. All patients will undergo periodic tumor assessments by CT or MRI scan every 12 weeks (3 months) from the start of the study treatment until progression / SPT or patient withdrawal. The primary endpoint is objective response rate (ORR) after 9 months of study treatment initiation according to RECIST V1.1. Secondary endpoints include disease control rate, duration of response, disease-free survival, overall survival, safety, patient reported outcomes and ancillary studies. The expected sample size is 25 patients calculated using a Simon II stage design (α = 0.1; β = 80%), taking as null hypothesis a 9-month ORR of 20% and an alternative ORR of 40%. The AFAN trial will investigate if afatinib is an effective treatment in FA patients with unresectable and / or metastatic locoregionally advanced squamous cell carcinoma of the oral cavity, oropharynx or hypopharynx or larynx.
publishDate 2025
dc.date.none.fl_str_mv 2
2025-01-01
2025
2025-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/319822
https://dx.doi.org/urn:doi:10.1186/s12885-025-14619-6
url https://ddd.uab.cat/record/319822
https://dx.doi.org/urn:doi:10.1186/s12885-025-14619-6
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 ICI22/00076
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869405156609622016
score 15,198674

Similar Items