Which generation of EGFR-targeting drugs does afatinib belong to? Differences from other targeted drugs

Afatinib is a second-generation EGFR-targeted drug that treats non-small cell lung cancer (NSCLC) and other diseases by irreversibly inhibiting EGFR and its mutants (including common EGFR Exon 19 deletions and L858R mutations). Compared with the first generation EGFR inhibitors (such as gefitinib and erlotinib), afatinib has a wider range of targets and can inhibit not only EGFR, but also HER2, HER4 and other receptors, which makes it equally effective for some patients with resistance to EGFR mutations.

The first generation of targeted drugs (such as gefitinib and erlotinib) inhibit the proliferation of tumor cells by competitively binding to the kinase site of EGFR. These drugs are generally effective against tumors with EGFR-sensitive mutations but are less effective against certain drug-resistant mutations, such as T790M. In contrast, afatinib's irreversible inhibitory effect can continuously act on EGFR and other related receptors, providing stronger anti-tumor effects, especially resistance to the T790M mutation. In addition, second-generation EGFR-targeted drugs such as afatinib have relatively high side effects, and common side effects such as rash and diarrhea are more prominent.

The third generationEGFR-targeted drugs, such as Osimertinib, specifically target the treatment of T790M mutation, and are especially suitable for drug-resistant patients after EGFR T790M mutation. Compared with afatinib, osimertinib has advantages in side effect control and is more selective in its therapeutic effect. Although afatinib is effective against a wider range of EGFR mutations, it is slightly inferior to third-generation drugs in the treatment of drug-resistant mutations.

In general, afatinib, as a second-generation EGFR-targeted drug, has a strong anti-tumor effect, and is especially effective against some drug-resistant mutations that are not easily controlled by first-generation drugs. Compared with other targeted drugs, its side effects are more obvious, so patients and doctors need to work together to formulate a reasonable treatment plan when using it.

Reference materials:https://www.giotrif.com/