Afatinib is a targeted therapy that irreversibly inhibits the ErbB family of tyrosine kinases.[1] 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).[1] 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.[2]
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.[3] Based on the reported data, afatinib is not superior to erlotinib in treating EGFR-mutant NSCLC.[3] However, afatinib was found to be more effective than erlotinib in treating advanced squamous cell carcinoma (as second-line treatment).[3]
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.[1] 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.[4]
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. The 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.[5]
This medication is available in the following form/doses:
For both non-small cell and squamous non-small cell metastatic cancers, dosing is 40 mg orally once daily, preferably more than an hour before or 2 hours after food.
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.[1] 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.[6]
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 warns against using this medication during breastfeeding, given potential serious adverse reactions in a breastfed infant.
Afatinib has the following monitoring requirements[7]:
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.[5]
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 dosing, close follow up with the 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. They can also perform medication reconciliation, verify dosing, and should report any issues to the prescribing physician or nursing staff. Nurses will encounter patients at followup visits and should document medication compliance as well as signs of adverse events, which they should communicate with the rest of the interprofessional healthcare team.
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. This collaboration demonstrates the clinical benefit of an interprofessional healthcare team. [Level V]
[1] | Keating GM, Afatinib: A Review in Advanced Non-Small Cell Lung Cancer. Targeted oncology. 2016 Dec; [PubMed PMID: 27873136] |
[2] | Lin NU,Winer EP,Wheatley D,Carey LA,Houston S,Mendelson D,Munster P,Frakes L,Kelly S,Garcia AA,Cleator S,Uttenreuther-Fischer M,Jones H,Wind S,Vinisko R,Hickish T, A phase II study of afatinib (BIBW 2992), an irreversible ErbB family blocker, in patients with HER2-positive metastatic breast cancer progressing after trastuzumab. Breast cancer research and treatment. 2012 Jun; [PubMed PMID: 22418700] |
[3] | Yang Z,Hackshaw A,Feng Q,Fu X,Zhang Y,Mao C,Tang J, Comparison of gefitinib, erlotinib and afatinib in non-small cell lung cancer: A meta-analysis. International journal of cancer. 2017 Jun 15; [PubMed PMID: 28295308] |
[4] | Li D,Ambrogio L,Shimamura T,Kubo S,Takahashi M,Chirieac LR,Padera RF,Shapiro GI,Baum A,Himmelsbach F,Rettig WJ,Meyerson M,Solca F,Greulich H,Wong KK, BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models. Oncogene. 2008 Aug 7; [PubMed PMID: 18408761] |
[5] | Wind S,Schnell D,Ebner T,Freiwald M,Stopfer P, Clinical Pharmacokinetics and Pharmacodynamics of Afatinib. Clinical pharmacokinetics. 2017 Mar; [PubMed PMID: 27470518] |
[6] | Niebecker R,Maas H,Staab A,Freiwald M,Karlsson MO, Modeling Exposure-Driven Adverse Event Time Courses in Oncology Exemplified by Afatinib. CPT: pharmacometrics [PubMed PMID: 30681293] |
[7] | Jobe AL,Ahonen KT,Poplin V,Rao S,Mohyuddin GR, Afatinib-induced Interstitial Lung Disease Successfully Treated with Corticosteroids: Case Report and Review of the Literature. Cureus. 2018 Jun 14; [PubMed PMID: 30123727] |