Impact of afatinib dose modification on safety and effectiveness in patients with EGFR mutation-positive advanced NSCLC: Results from a global real-world study (RealGiDo).

Autor: Halmos B; Department of Oncology, Montefiore/Albert Einstein Cancer Center, 2nd floor, 1695 Eastchester Rd, Bronx, NY, 10461, USA. Electronic address: bahalmos@montefiore.org., Tan EH; Division of Medical Oncology, National Cancer Centre Singapore, 11 Hospital Drive, 169610, Singapore. Electronic address: dmoteh@nccs.com.sg., Soo RA; Department of Haematology-Oncology, National University Hospital, Singapore (NCIS), Levels 8-10 @ NUH Medical Centre (NUHMC), 1 Kent Ridge Road, Singapore. Electronic address: ross_soo@nuhs.edu.sg., Cadranel J; Chest Department Hôpital Tenon and Sorbonne Université Paris VI, Service de Pneumologie, Hôpital Tenon, 4 rue de la Chine, Paris, 75970, France. Electronic address: jacques.cadranel@tnn.aphp.fr., Lee MK; Pusan National University Hospital, Pusan National University College of Medicine, Pusan, South Korea. Electronic address: leemk@pusan.ac.kr., Foucher P; Fédération d'Oncologie Thoracique, CHU Dijon-Bourgogne, Hôpital du Bocage, Centre Hospitalier Universitaire, 14, rue Gaffarel, 21079, Dijon Cedex, France. Electronic address: pascal.foucher@chu-dijon.fr., Hsia TC; Department of Internal Medicine, China Medical University Hospital, Division of Pulmonary and Critical Care Medicine, Taichung, Taiwan. Electronic address: derrick.hsia@msa.hinet.net., Hochmair M; Department of Respiratory and Critical Care Medicine, and Ludwig Boltzmann Institute of COPD and Respiratory Epidemiology, Otto-Wagner-Spital, Sanatoriumstrasse, 2, 1140 Vienna, Austria. Electronic address: maximilian.Hochmair@wienkav.at., Griesinger F; Department of Hematology and Oncology, Pius-Hospital, University Department Internal Medicine-Oncology, University of Oldenburg, Oldenburg, Germany. Electronic address: Frank.Griesinger@Pius-Hospital.de., Hida T; Department of Thoracic Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi 464-8681, Japan. Electronic address: 107974@aichi-cc.jp., Kim E; Department of Solid Tumor Oncology, Levine Cancer Institute, Atrium Health, Charlotte, NC, USA. Electronic address: Edward.kim@carolinashealthcare.org., Melosky B; Department of Medical Oncology, University of British Columbia, British Columbia Cancer Agency, BCCA, 600 W 10th Ave, Vancouver, Canada. Electronic address: bmelosky@bccancer.bc.ca., Märten A; Boehringer Ingelheim GmbH & Co. KG, Binger Straße 173, Ingelheim am Rhein, 55216, Germany. Electronic address: angela.maerten@boehringer-ingelheim.com., Carcereny E; Department of Medical Oncology, Catalan Institute of Oncology Badalona, Hospital Germans Trias i Pujol, Badalona, Spain. Electronic address: ecarcereny@iconcologia.net.
Jazyk: angličtina
Zdroj: Lung cancer (Amsterdam, Netherlands) [Lung Cancer] 2019 Jan; Vol. 127, pp. 103-111. Date of Electronic Publication: 2018 Nov 02.
DOI: 10.1016/j.lungcan.2018.10.028
Abstrakt: Objectives: In the LUX-Lung clinical trials of afatinib in EGFR mutation-positive NSCLC, tolerability-guided dose adjustment reduced the incidence and severity of adverse events while maintaining efficacy. The RealGiDo study evaluated the impact of afatinib dose adjustment in a real-world setting.
Materials and Methods: This non-interventional, observational study used medical records of EGFR mutation-positive NSCLC patients treated with first-line afatinib. Primary outcomes were adverse drug reaction (ADR) incidence and severity, time to treatment failure (TTF), and time to progression (TTP), relative to LUX-Lung 3 (LL3).
Results: 228 patients were enrolled from 13 countries. Baseline characteristics were in line with LL3 but with more Del19 patients (78.1% vs. 49.0%) and fewer Asian patients (43.9% vs. 72.2%); 11.8% had ECOG performance status 2-3. A total of 71 (31.1%) received a modified starting dose of ≤30 mg. Of patients who started with 40 mg, 67.1% underwent dose reductions, 86.5% of which were in the first 6 months. Dose reductions were mainly due to ADRs and were more common in female, East Asian, and low body-weight patients. There were no new safety signals and fewer ≥grade 3 ADRs (28.4% vs. 48.9%) and serious adverse events (5.2% vs. 14.0%) than in LL3. Median TTF and TTP were 18.7 and 20.8 months, respectively, and were not impacted by reduced starting dose or dose modification.
Conclusion: Real-world data show that afatinib dose adjustments reduced the frequency and intensity of ADRs without compromising effectiveness, highlighting the benefit of tailoring afatinib dose to optimise treatment outcomes and supporting clinical decision-making. The study is registered at clinicaltrials.gov (NCT02751879).
(Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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