Afatinib is a targeted therapy that irreversibly inhibits the ErbB family of tyrosine kinases. The first line FDA-approved indication is to treat locally advanced or metastatic non-small cell lung cancer (NSCLC) that harbor nonresistant epidermal growth factor receptor (EGFR) mutations. It is reported to be the second-line treatment of advanced squamous non-small cell lung cancer (NSCLC). Afatinib is also under investigation as monotherapy in patients with HER2-positive breast cancer who had progressed despite trastuzumab treatment. However, it does not yet have FDA approval.
There are three known tyrosine kinase inhibitors (EGFR TKIs) widely used as a treatment for advanced non-small cell lung cancer (NSCLC) with proven efficacy: Gefitinib, erlotinib, and afatinib. Based on the reported date, afatinib is not superior to erlotinib in treating EGFR-mutant NSCLC. However, afatinib was found to be more effective than erlotinib in treating advanced squamous cell carcinoma (as a second line treatment).
The mechanism of action of afatinib like other protein kinase inhibitors is to irreversibly inhibit epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and HER4. EGFR and HER2 are part of the receptor tyrosine kinase family and play significant roles in tumor cell proliferation as well as tumor vascularization. These receptors are known to exhibit overexpression in many types of cancer cell types. Afatinib also has activity against T790 mutations that are not sensitive to their standard therapies.
Afatinib is an orally administered drug, which is only available in tablet form. It should be taken on an empty stomach at least 1 hour before or 2 hours after a meal, as absorption decreases with high-fat meals. The tablet should be swallowed whole, with at least 8 ounces of water. The tablet should never be crushed or dissolved. Storage of this tablet should be at room temperature (68F to 77F). The recommended dosage is 40 mg tablets daily in a patient with normal creatinine and without any major liver dysfunction until disease progression, or the patient no longer tolerates it. Following oral administration, the time to peak plasma concentration (Tmax) is reported to be between 2 to 5 hours.
This medication is available in the form of
The treatment dosing adjustments for creatinine clearance:
The treatment dosage for hepatic impairment:
Afatinib has a predictable and manageable side effect profile based on a study by Keating et al. However, like other medications, it has a particular adverse event profile. The most common reported adverse events are diarrhea and rash/acne in 88% and 82% of patients, respectively.
The following side effects occurred in 1 to 10% of patients.
No known contraindications are listed in the manufacturer's labeling thus far. However, similar to many medications, prescribers should withhold dosing for any drug-related adverse reactions.
This drug requires permanent discontinuation in the event of:
This drug is not recommended during pregnancy, as no adequate clinical trials exist during pregnancy. Instead, A strong recommendation is that women of reproductive age should use an effective contraception method during therapy, and it should be continued at least for two weeks after the last dose of afatinib. The manufacturer argues against using this medication during breastfeeding given potential serious adverse reactions in a breastfed infant.
Afatinib has the following monitoring requirements:
There is not much research and data in regards to toxic and therapeutic levels of afatinib. However, it has been reported to have a predictable and manageable profile in terms of side effects.
Some serious adverse reactions have been identified, including hepatic impairment, dermatology complications, and rarely lung and cardiac complications. Afatinib should be dose adjusted in case of concomitant treatment with P-glycoprotein inducers or inhibitors.
Afatinib is a relatively new drug for the treatment of metastatic non-small cell lung cancer. Although, this drug easily can be administered by patients orally as once-daily drugs, close follow up with oncologist, and/or primary care physician, specialty-trained nurses, and pharmacist is necessary during the treatment. Pharmacists could be the best primary source for any questions or concerns by patients. Better communications between health care providers, patients, and pharmacists are recommended to improve patient care and also to build a better side effect profile for such a new drug, which eventually will lead to better patient care. [Level V]
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