Objectives Dacomitinib is a pan-HER inhibitor for advanced non-small-cell lung cancer (NSCLC). We explored the impact of a planned 4-day dacomitinib dose interruption on plasma exposure of dacomitinib and adverse events (AEs) of interest in Cohort III of the ARCHER 1042 study. Materials and methods Patients, treatment-naïve for advanced NSCLC with EGFR activating mutations, received oral dacomitinib 45 mg QD (once daily). A planned dose interruption occurred in Cycle 1 from Days 11 through 14. The primary endpoint was the pharmacokinetic (PK) characteristics of dacomitinib in Cycle 1 Day 10 and during dose interruption. Secondary endpoints included safety and concomitant medications used to treat AEs of interest. Results Cohort III enrolled 25 patients. Median plasma Cmax of dacomitinib in Cycle 1 Day 10 was 83.40 ng/mL. Average median plasma dacomitinib concentration during the 4-day dose interruption was 42.63 ng/mL. In the first 8 weeks of treatment 1) 80% of patients used concomitant medications for dermatologic AEs, 76% for diarrhea, and 44% for stomatitis, and 2) all patients experienced treatment-emergent AEs and 28% had all-causality Grade 3 AEs. Conclusion At 45 mg QD dosing, PK parameters of plasma dacomitinib in Cycle 1 Day 10 were comparable to that obtained in Cycle 1 Day 14 from other dacomitinib studies. Average median plasma dacomitinib concentration during the 4-day dose interruption was approximately half of the median plasma Cmax of dacomitinib observed prior to dose interruption. The toxicity profile was consistent with that from other studies of dacomitinib.
Bibliographical noteFunding Information:
EBG has received clinical trial funding to his institution from Pfizer, AstraZeneca, Eli Lilly, Genentech, Merck, Novartis, Bristol-Myers Squibb, and Boehringer Ingelheim. AJ has received research funding from Entera Health, Amgen, Boston Biologics, and Aveo Pharmaceuticals. DMK has received research funding from Helsinn and Entera Health, has been on a speaker bureau for Teva and Merck, is a co-investigator on a research project funded by Pfizer, and is on the scientific advisory board for Entrinsic Health. MEL has served as a consultant to Pfizer, Roche, and Genentech and has received research funding from Genentech, Roche, Bristol-Myers Squibb, and Berg and is partially funded through the NIH/NCI Cancer Center Support GrantP30-CA008748. DG, TW, NG, JPD, SN, and ES are employees of and own stock of Pfizer. JOC was an employee of Pfizer at the time of the study and owns stock of Pfizer. D-WK, SS, and BCC have no conflict of interest.
© 2017 Elsevier B.V.
All Science Journal Classification (ASJC) codes
- Pulmonary and Respiratory Medicine
- Cancer Research