Afatinib as first-line treatment in patients with EGFR-mutated non-small cell lung cancer in routine clinical practice

Wolfgang M Brückl; Martin Reck; Frank Griesinger; Harald Schäfer; Cornelius Kortsik; Tobias Gaska; Justyna Rawluk; Stefan Krüger; Konrad Kokowski; Stephan Budweiser; Joachim H Ficker; Christopher Hoffmann; Andrea Schüler; Eckart Laack

doi:10.1177/17588359211012361

Afatinib as first-line treatment in patients with EGFR-mutated non-small cell lung cancer in routine clinical practice

Ther Adv Med Oncol. 2021 May 6:13:17588359211012361. doi: 10.1177/17588359211012361. eCollection 2021.

Authors

Affiliations

¹ Department of Respiratory Medicine, Allergology and Sleep Medicine, Paracelsus Medical University, General Hospital Nuremberg, Ernst-Nathan-Str.1, Nuremberg, 90419, Germany.
² LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany.
³ Department of Hematology and Oncology, Pius Hospital, University Department Internal Medicine-Oncology, University Medicine, Oldenburg, Germany.
⁴ Department of Pneumonology, SHG-Clinic Voelklingen, Germany.
⁵ Department of Pneumonology, Catholic Hospital, Mainz, Germany.
⁶ Department of Hematology and Oncology, St. Josef Clinic, Paderborn, Germany.
⁷ Faculty of Medicine, University of Freiburg, Germany; Department of Hematology and Oncology, Medical Centre, University of Freiburg, Freiburg, Germany.
⁸ Department for Pneumology, Cardiology and Intensive Care Medicine, Florence-Nightingale-Hospital, Düsseldorf, Germany.
⁹ Department of Pneumonology, Bogenhausen Hospital, Munich, Germany.
¹⁰ Department of Internal Medicine III, Division of Pulmonary and Respiratory Medicine, RoMed Clinical Centre, Rosenheim, Germany.
¹¹ Department of Respiratory Medicine, Allergology and Sleep Medicine, Paracelsus Medical University, General Hospital Nuremberg, Nuremberg, Germany.
¹² Human Pharma Country Medical Affairs, Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany.
¹³ Hemato-Oncology Hamburg, Hamburg, Germany.

Abstract

Background: Lung cancer is a leading cause of cancer-related death in Germany and worldwide. Non-small cell lung cancer (NSCLC) comprises ~80% of lung cancer diagnoses; in White patients, around 10% of NSCLC cases are epidermal growth factor receptor mutation-positive (EGFRm+). Head-to-head clinical trials have demonstrated superior efficacy with second-/third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) versus first-generation EGFR TKIs in EGFRm+ NSCLC. Data from routine clinical practice are necessary to confirm that clinical trial findings are transferable to real-world populations.

Methods: In NCT02047903, a prospective non-interventional study in Germany, patients with EGFRm+ NSCLC received first-line afatinib until disease progression or intolerable adverse events. Key objectives were progression-free survival (PFS) rate at 12 months, objective response rate (ORR) and overall survival (OS). Safety/tolerability was also assessed.

Results: Of 152 patients, 106 (69.7%) were female, 20 (13.1%) patients had an uncommon EGFR mutation and 51 patients (33.6%) had brain metastases. A starting dose of <40 mg was received by 39 (25.7%) patients. Overall, the 12-month PFS rate was 50.2% while the median PFS was 12.2 months. The ORR was 74.6% and the median OS was 30.4 months. In patients with brain metastases and uncommon mutations, the median PFS was 10.5 and 10.7 months, and the ORR was 77.3% and 83.3%, respectively. Treatment effectiveness was similar in patients with a starting dose of <40 mg (median PFS: 16.4 months; ORR, 81.3%) and a starting dose of 40 mg (median PFS: 10.8 months; ORR, 72.1%). Adverse drug reactions were manageable and consistent with the known afatinib safety profile.

Conclusion: The results support clinical trial data for afatinib in routine clinical practice, including in patients generally excluded from clinical trials. Outcomes were positive in patients with uncommon EGFR mutations and in those with brain metastases. Treatment benefit was also seen in patients receiving a <40 mg afatinib starting dose, supporting patient-tailored dosing.

Keywords: EGFR mutation; afatinib; first-line; non-interventional study; non-small cell lung cancer.