Afatinib (Gilotrif)

General information

Class/mechanism: Irreversible tyrosine kinase inhibitor of EGFR (epidermal growth factor receptor, ErbB1), HER2 (human epidermal growth factor receptor 2, ErbB2), and HER4 (human epidermal growth factor receptor 4, ErbB4). Inhibition of tyrosine kinase autophosphorylation inhibits ErbB signaling.

Route: PO
Extravasation: n/a

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, UpToDate (courtesy of Lexicomp), or the prescribing information.

Diseases for which it is used

• Head and neck cancer
• EGFRm NSCLC
• Squamous NSCLC

Patient drug information

• Afatinib (Gilotrif) package insert
• Afatinib (Gilotrif) patient drug information (Chemocare)
• Afatinib (Gilotrif) patient drug information (UpToDate)

History of changes in FDA indication

• 2013-07-12: Approved for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor exon 19 deletion or exon 21 (L858R) substitution mutations as detected by an FDA-approved test. (Based on Clinical Trial Registry LUX-Lung 3])
• 2016-04-15: Approved for treatment of patients with metastatic, squamous NSCLC progressing after platinum-based chemotherapy. (Based on Clinical Trial Registry LUX-Lung 8])
• 2018-01-12: Approval expanded for a broadened indication in first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have non-resistant epidermal growth factor receptor mutations as detected by an FDA-approved test. (Based on Clinical Trial Registry LUX-Lung 2], Clinical Trial Registry LUX-Lung 3], and Clinical Trial Registry LUX-Lung 6])

History of changes in EMA indication

• 2013-09-25: Initial marketing authorization as Giotrif

History of changes in Health Canada indication

• 2013-11-01: Initial notice of compliance as monotherapy for the treatment of Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitor-naïve patients with metastatic (including cytologically proven pleural effusion) adenocarcinoma of the lung with activating EGFR mutation(s).
• 2016-08-25: New indication for second line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) of squamous histology.
• 2018-09-20: Updated indication (unclear)

History of changes in PMDA indication

• 2014-01-17: Initial approval for the treatment of unresectable advanced or recurrent non-small cell lung cancer with EGFR gene mutation.

Also known as

• Code names: BIBW 2992, BIBW-2992
• Generic name: afatinib dimaleate
• Brand names: Afanix, Gilotrif, Giotrif, Tomtovok, Tovok, Xovoltib