Afatinib: An overview of its clinical development in non-small-cell lung cancer and other tumors
Pasqualina Giordano1, Anna Manzo2, Agnese Montanino2
1Medical Oncology Unit, Thoracic Department, Istituto Nazionale Tumori, "Fondazione G. Pascale" - IRCCS, Napoli, Italy; Clinical Trials Unit, Istituto Nazionale Tumori, "Fondazione G.Pascale" - IRCCS, Napoli, Italy.
Abstract:
Afatinib is an oral, irreversible, tyrosine kinase inhibitor (TKI) of EGFR, HER2 and HER4. According to phase I studies, the recommended dose of afatinib was 50mg daily. Rash, acne, diarrhea and stomatitis were the most common adverse events. Afatinib failed to demonstrate an improvement in overall survival in unselected heavily pretreated NSCLC patients (Lux-Lung-1). On the contrary, the Lux-Lung-3 and -6 trials met the primary end point, demonstrating a significant increase in terms of PFS with afatinib compared with chemotherapy in the first line treatment of EGFR mutant patients. Moreover, in both studies, afatinib improved overall survival in patients with exon 19 EGFR deletion (31.7 vs 20.7 months; HR: 0.59, p=0.0001). The results of ongoing randomized trials should further clarify the efficacy of afatinib compared with first-generation TKIs in advanced NSCLC, its activity in the adjuvant and neoadjuvant settings, as well as its efficacy in other tumors.
Insights
Afatinib, a tyrosine kinase inhibitor, shows improved progression-free survival in EGFR-mutated non-small cell lung cancer (NSCLC) patients. It also improved overall survival in patients with specific EGFR deletions.
Area of Science:
- Oncology
- Pharmacology
Background:
- Afatinib is an irreversible tyrosine kinase inhibitor targeting EGFR, HER2, and HER4.
- Phase I studies established a 50mg daily dose, with rash, acne, diarrhea, and stomatitis as common adverse events.
Purpose of the Study:
- To evaluate the efficacy of afatinib in non-small cell lung cancer (NSCLC).
- To compare afatinib with chemotherapy in first-line treatment for EGFR-mutant NSCLC.
Main Methods:
- Analysis of data from Lux-Lung-1, Lux-Lung-3, and Lux-Lung-6 clinical trials.
- Comparison of progression-free survival (PFS) and overall survival (OS) between afatinib and chemotherapy groups.
Main Results:
- Afatinib did not improve OS in unselected, heavily pretreated NSCLC patients (Lux-Lung-1).
- Lux-Lung-3 and -6 trials demonstrated significantly increased PFS with afatinib versus chemotherapy in first-line EGFR-mutant NSCLC.
- Afatinib improved OS in patients with EGFR exon 19 deletion (31.7 vs 20.7 months; HR: 0.59).
Conclusions:
- Afatinib is effective in first-line treatment for EGFR-mutant NSCLC, particularly those with exon 19 deletions.
- Further trials are needed to clarify afatinib's efficacy against first-generation TKIs, in adjuvant/neoadjuvant settings, and in other cancers.
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