BMC Cancer. 2025 Aug 26;25(1):1374. doi: 10.1186/s12885-025-14619-6.
ABSTRACT
BACKGROUND: 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.
METHODS: 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%.
DISCUSSION: 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.
TRIAL REGISTRATION: EU CT 20,245,114,772,900 / www.
CLINICALTRIALS: gov NCT06648096 (August, 1st 2024).
PMID:40859225 | DOI:10.1186/s12885-025-14619-6
