Jeff A Engle1, Jill M Kolesar2. 1. Jeff A. Engle, B.S., is a Pharm.D. student, School of Pharmacy, University of Wisconsin (UW)-Madison, Madison. Jill M. Kolesar, Pharm.D., BCPS, FCCP, is Professor, School of Pharmacy, UW-Madison, and Faculty Supervisor, Analytical Laboratory for Pharmacokinetics, Pharmacodynamics, and Pharmacogenomics, UW Carbone Comprehensive Cancer Center, Madison. 2. Jeff A. Engle, B.S., is a Pharm.D. student, School of Pharmacy, University of Wisconsin (UW)-Madison, Madison. Jill M. Kolesar, Pharm.D., BCPS, FCCP, is Professor, School of Pharmacy, UW-Madison, and Faculty Supervisor, Analytical Laboratory for Pharmacokinetics, Pharmacodynamics, and Pharmacogenomics, UW Carbone Comprehensive Cancer Center, Madison. jmkolesar@pharmacy.wisc.edu.
Abstract
PURPOSE: The pharmacology, pharmacokinetics, clinical efficacy, safety, adverse effects, dosage and administration, and role in therapy of afatinib in the management of non-small-cell lung cancer (NSCLC) are reviewed. SUMMARY: Afatinib (Gilotrif, Boehringer Ingelheim) is a novel oral tyrosine kinase inhibitor (TKI) recently approved for the first-line treatment of patients with NSCLC whose tumors are driven by activating mutations of genes coding for epidermal growth factor receptor (EGFR). Afatinib is also an inhibitor of a specific EGFR mutation (T790M) that causes resistance to first-generation EGFR-targeted TKIs in about half of patients receiving those drugs. The recommended dosage is 40 mg once daily. In a Phase III trial completed last year, patients with EGFR-mutated NSCLC who were treated with afatinib had a twofold higher response rate than those receiving standard combination chemotherapy (56% versus 23%) and significantly longer progression-free survival (11.0 months versus 5.6 months). Other studies indicated that afatinib may offer advantages over standard chemotherapy for NSCLC in terms of enhanced symptom control and quality of life and is modestly effective in cases involving EGFRT790M-related acquired resistance to the TKIs erlotinib and gefitinib. Among clinical trial participants, afatinib was generally well tolerated, with the most common grade I or II adverse events being diarrhea and rash or acne; grade III or IV events were infrequent. CONCLUSION: Afatinib is a novel TKI that is efficacious and well tolerated in patients with NSCLC associated with activating EGFR mutations, including cases involving the T790M resistance mutation. It has possible applications in other EGFR mutation- positive cancers.
PURPOSE: The pharmacology, pharmacokinetics, clinical efficacy, safety, adverse effects, dosage and administration, and role in therapy of afatinib in the management of non-small-cell lung cancer (NSCLC) are reviewed. SUMMARY:Afatinib (Gilotrif, Boehringer Ingelheim) is a novel oral tyrosine kinase inhibitor (TKI) recently approved for the first-line treatment of patients with NSCLC whose tumors are driven by activating mutations of genes coding for epidermal growth factor receptor (EGFR). Afatinib is also an inhibitor of a specific EGFR mutation (T790M) that causes resistance to first-generation EGFR-targeted TKIs in about half of patients receiving those drugs. The recommended dosage is 40 mg once daily. In a Phase III trial completed last year, patients with EGFR-mutated NSCLC who were treated with afatinib had a twofold higher response rate than those receiving standard combination chemotherapy (56% versus 23%) and significantly longer progression-free survival (11.0 months versus 5.6 months). Other studies indicated that afatinib may offer advantages over standard chemotherapy for NSCLC in terms of enhanced symptom control and quality of life and is modestly effective in cases involving EGFRT790M-related acquired resistance to the TKIs erlotinib and gefitinib. Among clinical trial participants, afatinib was generally well tolerated, with the most common grade I or II adverse events being diarrhea and rash or acne; grade III or IV events were infrequent. CONCLUSION:Afatinib is a novel TKI that is efficacious and well tolerated in patients with NSCLC associated with activating EGFR mutations, including cases involving the T790M resistance mutation. It has possible applications in other EGFR mutation- positive cancers.
Authors: Claudia Vollbrecht; Robert Werner; Robert Fred Henry Walter; Daniel Christian Christoph; Lukas Carl Heukamp; Martin Peifer; Burkhard Hirsch; Lina Burbat; Thomas Mairinger; Kurt Werner Schmid; Jeremias Wohlschlaeger; Fabian Dominik Mairinger Journal: Br J Cancer Date: 2015-12-08 Impact factor: 7.640