Afatinib, sold under the brand name Gilotrif among others, is a medication 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 treat cases of NSCLC that harbour mutations in the epidermal growth factor receptor (EGFR) gene.It is on the World Health Organizations List of Essential Medicines. 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:
Very common (>10% frequency)

Common (1–10% frequency)

Uncommon (0.1-1% frequency)
Keratitis
Interstitial lung disease

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. 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.
Mechanism of action
Recently, it has been shown that trabectedin blocks DNA binding of the oncogenic transcription factor FUS-CHOP and reverses the transcriptional program in myxoid liposarcoma. By reversing the genetic program created by this transcription factor, trabectedin promotes differentiation and reverses the oncogenic phenotype in these cells.Other than transcriptional interference, the mechanism of action of trabectedin is complex and not completely understood. The compound is known to bind and alkylate DNA at the N2 position of guanine. It is known from in vitro work that this binding occurs in the minor groove, spans approximately three to five base pairs and is most efficient with CGG sequences. Additional favorable binding sequences are TGG, AGC, or GGC. Once bound, this reversible covalent adduct bends DNA toward the major groove, interferes directly with activated transcription, poisons the transcription-coupled nucleotide excision repair  complex, promotes degradation of RNA polymerase II, and generates DNA double-strand breaks. Society and culture
Legal status
In September 2020, the European Medicines Agency recommended that the use of trabectedin in treating ovarian cancer remain unchanged. == References ==