Jesús Corral1, Tony S Mok2, Kazuhiko Nakagawa3, Rafael Rosell4, Ki Hyeong Lee5, Maria Rita Migliorino6, Adam Pluzanski7, Rolf Linke8, Geeta Devgan9, Weiwei Tan10, Susan Quinn11, Tao Wang12, Yi-Long Wu13. 1. Clínica Universidad de Navarra, Madrid, 28027, Spain. 2. State Key Laboratory of South China, Department of Clinical Oncology, Chinese University of Hong Kong, Hong Kong, PR China. 3. Kindai University Hospital, Osaka, 589-8511, Japan. 4. Catalan Institute of Oncology, Barcelona, Spain. 5. Chungbuk National University Hospital, Cheongju, Korea. 6. Pulmonary Oncology Unit, San Camillo-Forlanini Hospital, Rome, 00152, Italy. 7. The Maria Sklodowska-Curie Memorial Cancer Centre & Institute of Oncology, Warsaw, 02-781, Poland. 8. SFJ Pharmaceuticals®, Pleasanton, CA 94588, USA. 9. Pfizer Oncology, New York, NY 10017, USA. 10. Pfizer Clinical Pharmacology, San Diego, CA 92121, USA. 11. Pfizer Oncology, Cambridge, MA 02139, USA. 12. Pfizer Oncology, Groton, CT 06340, USA. 13. Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, PR China.
Abstract
Aim: We evaluated reasons for dacomitinib dose reduction (DR) and examined adverse event (AE) incidence, key efficacy end points (progression-free survival [PFS]/overall survival [OS]), and pharmacokinetics in dose-reducing patients in the ARCHER 1050 trial. Patients & methods: Newly diagnosed patients with EGFR mutation-positive, advanced non-small-cell lung cancer received oral dacomitinib (45 mg once-daily [QD]), with stepwise toxicity-managing DR (30 and 15 mg QD) permitted. Results: Skin toxicities (62.7%) were the most common DR-leading AEs. The AE incidence and severity decreased following DRs. Initial plasma dacomitinib exposure (45 mg QD) was generally lower in patients remaining at 45 mg QD compared with dose-reducing patients. Median PFS and OS were similar in all dacomitinib-treated patients and dose-reducing patients. Conclusion: Tolerability-guided dose modifications enabled patients to continue with dacomitinib and benefit from PFS/OS improvement. Trial registration number: NCT01774721.
Aim: We evaluated reasons for dacomitinib dose reduction (DR) and examined adverse event (AE) incidence, key efficacy end points (progression-free survival [PFS]/overall survival [OS]), and pharmacokinetics in dose-reducing patients in the ARCHER 1050 trial. Patients & methods: Newly diagnosed patients with EGFR mutation-positive, advanced non-small-cell lung cancer received oral dacomitinib (45 mg once-daily [QD]), with stepwise toxicity-managing DR (30 and 15 mg QD) permitted. Results:Skin toxicities (62.7%) were the most common DR-leading AEs. The AE incidence and severity decreased following DRs. Initial plasma dacomitinib exposure (45 mg QD) was generally lower in patients remaining at 45 mg QD compared with dose-reducing patients. Median PFS and OS were similar in all dacomitinib-treated patients and dose-reducing patients. Conclusion: Tolerability-guided dose modifications enabled patients to continue with dacomitinib and benefit from PFS/OS improvement. Trial registration number: NCT01774721.