• Written informed consent according to local guidelines, must be signed and dated by the participant and investigator prior to performing any protocol procedure.

• Patient is ≥ 18 years of age.

• Confirmed diagnosis of Fanconi anemia.

• Histologically or cytologically confirmed unresectable or locoregionally advanced squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, larynx, nasopharynx, paranasal sinuses or salivary glands. Patients with distal metastasis (M1, American Joint Cancer Committee (AJCC) 8th ed.) are also eligible.

• Tumor not a candidate for resection prior to Afatinib due to technical inability to resect (tumor fixation / invasion in the skull base, cervical vertebrae, nasopharynx or fixed lymph nodes) and / or low surgical cure \[T3-T4, N2-N3; , AJCC 8th ed.\]).

• Patients must have at least 1 measurable lesion by computed tomography (CT) scan or magnetic resonance imaging (MRI) as defined by RECIST v1.1.

• Previous anticancer treatment is allowed if it ends 6 weeks or 5 half-lives, whichever is shorter, before the expected date of start of the study treatment.

• Previous locoregional treatments such as radiotherapy are allowed.

• Eastern Cooperative Oncology Group (ECOG) performance status \< 2 at inclusion.

⁃ Adequate organ and bone marrow functions, as defined below:

∙ Neutrophils \> 1000 cells / microliter.

‣ Platelets \> 50,000 cells / microliter.

‣ Hemoglobin \> 8 g / dL

‣ Creatinine \< 1.5 x upper limit normal (ULN) with clearance \> 50 mL / min.

‣ Total bilirubin \< 1.5 x ULN. Note: patients with Gilbert's may be included with bilirubin \<2 x ULN.

‣ Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 2.5 x ULN or \< 5 ULN if liver metastases are present.

‣ International normalized ratio (INR) and prothrombin time (PT) \<1.5 x ULN.

⁃ Female patients must either:

∙ Be of non-childbearing potential:

∙ Postmenopausal \*(defined as at least 1 year without any menses) prior to screening , or Documented surgically sterile (e.g.hysterectomy, bilateral salpingectomy, bilateral oophorectomy, or bilateral tubal occlusion).

∙ \*Those who are amenorrheic due to an alternative medical cause are not considered postmenopausal and must follow the criteria for childbearing potential subjects.

∙ OR

‣ If of childbearing potential:

⁃ Agree not to try to become pregnant during the study and for at least 1 months after the final study drug administration, And have a negative urine or serum pregnancy test within 7 days prior to Day 1 (females with false positive results and documented verification of negative pregnancy status are eligible for participation), And if heterosexually active, agree to abstinence (if in line with the usual preferred lifestyle of the patient) or consistently use a condom plus 1 form of highly effective birth control per locally accepted standards starting at screening and throughout the study period and for at least 1 month after the final study drug administration.

⁃ Female patients must agree not to breastfeed or donate ovules starting at screening and throughout the study period, and for at least 1 month after the final study drug administration.

⁃ Male patients must not donate sperm starting at screening and throughout the study period, and for at least 1 month after the final study drug administration.

⁃ Male patients with a partner with childbearing potential, or who is pregnant or breastfeeding must agree to abstinence or use a condom plus 1 form of highly effective birth control throughout the study period and for at least 1 month after the final study drug administration.

⁃ Patient agrees not to participate in another interventional study while on treatment in the present study.