Original Articles
Efficacy of the Irreversible ErbB Family Blocker Afatinib in Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor (TKI)–Pretreated Non–Small-Cell Lung Cancer Patients with Brain Metastases or Leptomeningeal Disease

https://doi.org/10.1097/JTO.0000000000000380Get rights and content
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Introduction

Afatinib is an effective first-line treatment in patients with epidermal growth factor receptor (EGFR)-mutated non–small-cell lung cancer (NSCLC) and has shown activity in patients progressing on EGFR-tyrosine kinase inhibitors (TKIs). First-line afatinib is also effective in patients with central nervous system (CNS) metastasis. Here we report on outcomes of pretreated NSCLC patients with CNS metastasis who received afatinib within a compassionate use program.

Methods

Patients with NSCLC progressing after at least one line of chemotherapy and one line of EGFR-TKI treatment received afatinib. Medical history, patient demographics, EGFR mutational status, and adverse events including tumor progression were documented.

Results

From 2010 to 2013, 573 patients were enrolled and 541 treated with afatinib. One hundred patients (66% female; median age, 60 years) had brain metastases and/or leptomeningeal disease with 74% having documented EGFR mutation. Median time to treatment failure for patients with CNS metastasis was 3.6 months, and did not differ from a matched group of 100 patients without CNS metastasis. Thirty-five percent (11 of 31) of evaluable patients had a cerebral response, five (16%) responded exclusively in brain. Response duration (range) was 120 (21–395) days. Sixty-six percent (21 of 32) of patients had cerebral disease control on afatinib. Data from one patient with an impressive response showed an afatinib concentration in the cerebrospinal fluid of nearly 1 nMol.

Conclusion

Afatinib appears to penetrate into the CNS with concentrations high enough to have clinical effect on CNS metastases. Afatinib may therefore be an effective treatment for heavily pretreated patients with EGFR-mutated or EGFR–TKI-sensitive NSCLC and CNS metastasis.

Key Words

Afatinib
ErbB family blocker
Central nervous system metastasis
Non–small-cell lung cancer
Compassionate use program

Cited by (0)

Dr. Hoffknecht has participated in boards for Lilly Oncology and has received institutional grant support and compensation for travel expenses from Boehringer Ingelheim. Dr. Tufman has received compensation for lectures from Boehringer Ingelheim, Eli Lilly, Roche, and Novartis. Dr. Wehler has served as consultant and participated in boards and has received compensation for lectures and educational presentations from Boehringer Ingelheim, Eli Lilly, Pfizer, Roche, and Bristol-Myers Squibb. Dr. Wiewrodt has participated in investigator-initiated trials for Bayer and Eli Lilly and advisory boards for Boehringer Ingelheim Grifols, Eli Lilly, Novartis, Roche, and Talecris. Dr. Wiewrodt has also received compensation for lectures and CME from Bayer, Boehringer Ingelheim, EuMeCom, Grifols, GlaxoSmithKline, Eli Lilly, MSD, Novartis, Pfizer, Roche, Talecris, UKM Academy, and ZDF. Dr. Schütz has participated in advisory boards for Boehringer Ingelheim. Dr. Serke has participated in boards and received compensation for lectures from Boehringer Ingelheim, Eli Lilly, Pfizer, and Roche and has received honoraria for participation in review activities from Boehringer Ingelheim, Eli Lilly, Pfizer, Roche, AstraZeneca, and Amgen. Dr. Stöhlmacher-Williams has served as consultant and received compensation for lectures and previous manuscript preparation from Boehringer Ingelheim. Dr. Märten is a full-time employee of Boehringer Ingelheim Pharma GmbH & Co KG. Dr. Huber has served as consultant for Boehringer Ingelheim and has received compensation for lectures from Boehringer Ingelheim, Pfizer, and Pierre Fabre Pharma GmbH. Dr. Dickgreber has participated in boards for Boehringer Ingelheim, Eli Lilly, Roche, Novartis, and Bristol-Myers Squibb and has served as consultant and provided expert testimony for Boehringer Ingelheim, Eli Lilly, and Roche. Dr. Pelzer declares no conflicts of interest.

1

Drs. Hoffknecht and Tufman contributed equally to this work.

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Members of the Afatinib Compassionate Use Consortium (ACUC) are listed in Appendix