Afatinib Explained

Afatinib should not be confused with apatinib.

Afatinib, sold under the brand name Gilotrif among others, is a medication which is used to treat non-small cell lung carcinoma (NSCLC). It belongs to the tyrosine kinase inhibitor family of medications. It is taken by mouth.

It is mainly used to treating cases of NSCLC that harbour mutations in the epidermal growth factor receptor (EGFR) gene.[1]

It is on the World Health Organization's List of Essential Medicines.[2]

Medical uses

It has received regulatory approval for use as a treatment for non-small cell lung cancer, although there is emerging evidence to support its use in other cancers such as breast cancer.

Adverse effects

Adverse effects by frequency include:[3] [4] [5] [6] [7]

Very common (>10% frequency):
Common (1–10% frequency):
Uncommon (0.1-1% frequency):

Mechanism of action

Like lapatinib and neratinib, afatinib is a protein kinase inhibitor that also irreversibly inhibits human epidermal growth factor receptor 2 (Her2) and epidermal growth factor receptor (EGFR) kinases. Afatinib is not only active against EGFR mutations targeted by first generation tyrosine-kinase inhibitors (TKIs) like erlotinib or gefitinib, but also against less common mutations which are resistant to these drugs. However, it is not active against the T790M mutation which generally requires third generation drugs like osimertinib.[8] Because of its additional activity against Her2, it is being investigated for breast cancer as well as other EGFR and Her2 driven cancers.

Clinical trials

In March 2010, a Phase III trial in NSCLC patients called Lux-Lung 5 began with this drug.Fall 2010 interim results suggested the drug extended progression-free survival threefold compared to placebo, but did not extend overall survival. In May 2012, the Phase IIb/III trial Lux-Lung 1 came to the same conclusion.

In January 2015, a Phase III trial in people with NSCLC suggested the drug extended life expectancy in stage IV NSCLC adenocarcinoma with EGFR Mutation type del 19-positive tumors, compared to cisplatin-based chemotherapy by a year (33 months vs. 21 months).[9] It also shows strong activity against exon 18 mutations (particularly G719) and is currently the preferred EGFR-TKI therapy for exon 18 mutations (particularly G719x).[10]

Phase II results for breast cancer that over-expresses the protein human epidermal growth factor receptor 2 (Her2-positive breast cancer) were described as promising by the authors, with 19 of 41 patients achieving benefit from afatinib. Double-blind Phase III trials are under way to confirm or refute this finding. Her2-negative breast cancers showed limited or no response to the drug.

Society and culture

Brand names

In Bangladesh under the trade name Afanix.

External links

Notes and References

  1. Vavalà T . Role of afatinib in the treatment of advanced lung squamous cell carcinoma . Clinical Pharmacology . 9 . 147–157 . 2017 . 29225480 . 5709991 . 10.2147/CPAA.S112715 . free .
  2. Book: ((World Health Organization)) . World Health Organization model list of essential medicines: 22nd list (2021) . 2021 . 10665/345533 . World Health Organization . World Health Organization . Geneva . WHO/MHP/HPS/EML/2021.02 . free .
  3. Web site: Gilotrif (afatinib) tablet, film coated . DailyMed. Boehringer Ingelheim Pharmaceuticals, Inc.. 18 October 2019 . 4 November 2020.
  4. Web site: Giotrif Afatinib (as afatinib dimaleate). TGA eBusiness Services. Boehringer Ingelheim Pty Limited. 7 November 2013. 28 January 2014. PDF.
  5. Web site: Giotrif 20 mg film-coated tablets – Summary of Product Characteristics (SPC). electronic Medicines Compendium. Boehringer Ingelheim Limited. 20 January 2014. 28 January 2014.
  6. Web site: Giotrif : EPAR -Product Information. European Medicines Agency. Boehringer Ingelheim International GmbH. 16 October 2013. 28 January 2014.
  7. Web site: Gilotrif (afatinib) dosing, indications, interactions, adverse effects, and more. Medscape Reference. WebMD. 28 January 2014.
  8. 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 . 6 . BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models . Oncogene . 27 . 34 . 4702–11 . August 2008 . 18408761 . 2748240 . 10.1038/onc.2008.109 .
  9. Yang JC, Wu YL, Schuler M, Sebastian M, Popat S, Yamamoto N, Zhou C, Hu CP, O'Byrne K, Feng J, Lu S, Huang Y, Geater SL, Lee KY, Tsai CM, Gorbunova V, Hirsh V, Bennouna J, Orlov S, Mok T, Boyer M, Su WC, Lee KH, Kato T, Massey D, Shahidi M, Zazulina V, Sequist LV . 6 . Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials . The Lancet. Oncology . 16 . 2 . 141–51 . February 2015 . 25589191 . 10.1016/s1470-2045(14)71173-8 .
  10. Kobayashi Y, Togashi Y, Yatabe Y, Mizuuchi H, Jangchul P, Kondo C, Shimoji M, Sato K, Suda K, Tomizawa K, Takemoto T, Hida T, Nishio K, Mitsudomi T . 6 . EGFR Exon 18 Mutations in Lung Cancer: Molecular Predictors of Augmented Sensitivity to Afatinib or Neratinib as Compared with First- or Third-Generation TKIs . Clinical Cancer Research . 21 . 23 . 5305–13 . December 2015 . 26206867 . 10.1158/1078-0432.CCR-15-1046 . free .

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