Publication-only abstracts (abstract number preceded by an "e"), published in conjunction with the 2018 ASCO Annual Meeting but not presented at the Meeting, can be found online only.
Real-world dose adjustment study of first-line afatinib in pts with EGFR mutation-positive (EGFRm+) advanced NSCLC.
Metastatic Non-Small Cell Lung Cancer
Lung Cancer—Non-Small Cell Metastatic
2018 ASCO Annual Meeting
J Clin Oncol 36, 2018 (suppl; abstr e21060)
Author(s): Balazs Halmos, Eng-Huat Tan, Min Ki Lee, Pascal Foucher, Te-Chun Hsia, Maximilian J. Hochmair, Frank Griesinger, Toyoaki Hida, Edward S. Kim, Barbara L. Melosky, Angela Maerten, Enric Carcereny Costa; Department of Oncology, Montefiore/Albert Einstein Cancer Center, Bronx, NY; National Cancer Centre Singapore, Singapore, Singapore; Pusan National University Hospital, Pusan National University College of Medicine, Pusan, Korea, Republic of (South); Fédération d'Oncologie Thoracique, CHU Dijon-Bourgogne, Hôpital du Bocage, Dijon, France; Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan; Department of Respiratory and Critical Care Medicine, Otto-Wagner-Spital, Vienna, Austria; Department of Hematology and Oncology, Pius-Hospital, University Department Internal Medicine-Oncology, University of Oldenburg, Oldenburg, Germany; Department of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya, Japan; Department of Solid Tumor Oncology and Investigational Therapeutics, Levine Cancer Institute, Atrium Health, Charlotte, NC; Department of Medical Oncology, University of British Columbia, Vancouver, BC, Canada; Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim Am Rhein, Germany; Department of Medical Oncology, Catalan Institute of Oncology Badalona-Hospital Germans Trias I Pujol, Badalona, Spain
Background: Tolerability-guided dose adjustment of afatinib reduced the incidence and severity of adverse drug reactions (ADRs) without affecting efficacy in the LUX-Lung (LL) studies in EGFRm+ NSCLC. We report the impact of afatinib dose modifications on efficacy and safety in a real-world setting. Methods: This non-interventional, observational, multi-country/site study used medical records of TKI-naïve pts with EGFRm+ (Del19/L858R) NSCLC treated with first-line afatinib. Primary outcomes were % pts with ADRs by severity, time on treatment, and time to progression (TTP; where reported), relative to LL3. Secondary outcomes were % pts with/reasons for modified starting dose. Results: 228 pts from 13 countries were included. Baseline characteristics were in line with LL3, but with more Del19 pts (78% vs 49%); 12% had ECOG PS 2–3. 31% started with <40 mg, mainly due to the pt’s condition. Dose modifications were more frequent in females, older pts, Eastern Asian pts, and lower body weight pts. 51% of pts were still on treatment; main reason for discontinuation was PD (33% overall). 67% of ≥40 mg starters underwent dose reductions, with 86% of those occurring in the first 6 mos. 12% (28) pts increased dose. The main reason for dose modification was ADRs. In ≤30 mg starters, overall ADR incidence was similar to ≥40 mg starters, with fewer G3 (17% vs 25%) and no G4 ADRs. There were no new safety signals, and fewer ≥G3 ADRs and SAEs than in LL3 (25% vs 49% and 5% vs 14%). >60% of the pts received medications to treat diarrhea and manage skin AEs. Median time on treatment and TTP was 18.7 mos and 20.8 mos respectively and was not impacted by reduced starting dose or dose modification (19.4/17.7/19.5 and 25.9/20.0/29.0 mos for pts who started on ≤30 mg/reduced to <40 mg/remained on ≥40 mg). Conclusions: As in LL trials, real-world afatinib dose adjustments reduced the frequency and intensity of ADRs without impacting efficacy. Time on treatment/TTP were similar regardless of dose adjustment or reduced starting dose, confirming the efficacy of this regimen with an acceptable safety profile. The results highlight the benefit of tailoring afatinib dose based on individual pt characteristics and ADRs to optimize outcomes. Clinical trial information: NCT02751879
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