Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2018

Impact of afatinib dosing on safety and efficacy in patients with EGFR mutation-positive advanced Non-Small Cell Lung Cancer (NSCLC) in a real-world setting (#338)

Balazs Halmos 1 , Eng-Huat Tan 2 , Ross Soo 3 , Jacques Cadranel 4 , Min Ki Lee 5 , Pascal Foucher 6 , Te-Chun Hsia 7 , Maximilian Hochmair 8 , Frank Griesinger 9 , Toyoaki Hida 10 , Edward Kim 11 , Barbara Melosky 12 , Angela Maerten 13 , Enric Carcereny 14
  1. Department of Oncology, Montefiore/Albert Einstein Cancer Center, New York, U.S.A
  2. Division of Medical Oncology, National Cancer Centre Singapore, Singapore
  3. Department of Haematology-Oncology, National University Hospital, Singapore
  4. Chest Department, Hôpital Tenon and Sorbonne Université , Paris, France
  5. Pusan National University Hospital, Pusan National University College of Medicine, Pusan, South Korea
  6. Fédération d'Oncologie Thoracique, CHU Dijon-Bourgogne, Hôpital du Bocage, Dijon, France
  7. Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
  8. Department of Respiratory and Critical Care Medicine, Otto-Wagner-Spital, Vienna, Austria
  9. Department of Hematology and Oncology, Pius-Hospital, University Department Internal Medicine-Oncology, University of Oldenburg, Oldenburg, Germany
  10. Department of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya, Japan
  11. Department of Solid Tumor Oncology, Levine Cancer Institute, Carolinas HealthCare System, Charlotte, North Carolina
  12. Department of Medical Oncology, University of British Columbia, Vancouver, Canada
  13. Boehringer Ingelheim GmbH & Co. KG, Ingelheim am Rhein, Germany
  14. Department of Medical Oncology, Catalan Institute of Oncology Badalona-Hospital Germans Trias I Pujol, Badalona, Spain


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 EGFR mutation-positive (EGFRm+) NSCLC. We evaluated the impact of modifying the recommended starting dose of afatinib (40mg) on efficacy and safety in a real-world setting.  



This non-interventional, observational, multi-country/site study used medical records of TKI-naïve patients with EGFRm+ (Del19/L858R) NSCLC treated with first-line afatinib. Primary outcomes were incidence of ADRs, time on treatment (TT), and time to progression (TTP), relative to LL3. Secondary outcomes were percentage of patients with/reasons for modified starting dose.



Overall, 228 patients from 13 countries were included. Baseline characteristics were similar to LL3, but with more Del19 (78% vs. 49%) and fewer Asian patients (44% vs. 72%); 12% had ECOG PS2/3; 31% received afatinib starting doses of <40mg, 20% of whom increased their dose during the study. Of the 40mg starters, 67% underwent dose reductions which occurred more frequently in females, Eastern-Asian patients, and in those with lower body weight. ADRs were the main reason for dose modifications; overall ADR incidence in the
<40mg starters was similar to ≥40mg starters, with fewer ≥G3 ADRs and SAEs than LL3 (28% vs. 49% and 5% vs. 14%, respectively). Median TT and TTP (18.7 and 20.8 months, respectively) were not impacted by dose adjustments. The effectiveness of afatinib was demonstrated across all patient subgroups (ECOG PS0/1 vs. 2/3, age <75 vs. ≥75 years, EGFRm); TT and TTP were significantly longer in patients with ECOG PS0/1 vs. PS2/3.



Dose adjustments with afatinib in real-world practice reduced the frequency and intensity of ADRs without impacting efficacy. A long TT/TTP regardless of afatinib dose adjustments, and an acceptable safety profile highlighted the benefit of tailoring afatinib dose based on individual patient characteristics and ADRs.