Gefitinib and erlotinib are the two anti-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) approved for treatment of advanced NSCLC patients. These drugs target one of the most important pathways in lung carcinogenesis and are able to exploit the phenomenon of "oncogene addiction", with different efficacy according to EGFR gene mutational status in tumor samples. Gefitinib has been approved only for EGFR mutation bearing patients regardless the line of treatment, while erlotinib is also indicated in patients without EGFR mutation who undergo second- or third-line treatment.

Figure 1. Mechanism of action of EGFR inhibitors^[1]

Differences

Gefitinib and erlotinib are orally active EGFR TKIs with different structure, as also reflected by the different molecular weight (446.9 Da and 429.9 Da, respectively). These drugs are ATP competitors at the ATP-binding pocket in the intracellular domain of EGFR. As a consequence of this inhibition, cellular proliferation, angiogenesis, tumor invasion, and metastatic potential are inhibited. Gefitinib is available as film-coated tablets that contain 250 mg of active compound. Erlotinib tablets are available in three dose strengths: 25 mg, 100 mg, and 150 mg.

Similarity

In the last years the introduction of the anti-EGFR TKIs gefitinib and erlotinib represented the most important innovation for the treatment of advanced NSCLC. Infact these drugs are able to target the main pathway involved in lung cancer development and progression, the EGFR-mediated signaling transduction pathway. Furthermore TKIs allow sparing these patients from chemotherapy and subsequent quality-of-life-impairing toxicities. However in the first-line treatment only patients bearing EGFR gene activating mutations could achieve more benefit than chemotherapy. Since gefitinib and erlotinib have different structure and subsequently different affinity with their receptor, toxicity frequency, but similar efficacy results, researchers postulated that these drugs could be partially interchangeable in the decision making for EGFR-mutated advanced NSCLC patients who will undergo a cancer treatment.[2]

References

[1] EGFR Signaling and its inhibition by EGFR inhibitors in NSCLC. doi:10.3126/ijasbt.v2i4.11263

[2] Are erlotinib and gefitinib interchangeable, opposite or complementary for non-small cell lung cancer treatment? Biological, pharmacological and clinical aspects. doi:10.1016/j.critrevonc.2013.08.003