Objectives: Epidermal growth factor receptor (EGFR) exon 20 insertions comprise 4–10 % of EGFR mutations in non-small cell lung cancer (NSCLC) and are associated with primary resistance to first and second generation EGFR tyrosine kinase inhibitors (TKIs). In vitro and preclinical animal studies have shown that osimertinib exerts antitumor activity against EGFR exon 20 mutation positive NSCLC. We report on a cohort of advanced stage NSCLC patients who harbor an EGFR exon 20 mutation and received osimertinib treatment. Material and methods: Twenty-one patients were treated with osimertinib 80 or 160 mg once daily from April 2016 to June 2018, in four institutions in the Netherlands. Data were obtained retrospectively. Progression free survival (PFS), disease control rate (DCR), overall survival (OS) and objective response rate (ORR) were assessed using RECIST v1.1. Results: Thirteen patients received prior platinum-based chemotherapy, and three patients a first – or second generation EGFR TKI. We observed 1 partial response, 17 patients with stable disease and 3 with progressive disease as best response to osimertinib (ORR 5 %). Median PFS was 3.6 (95 % CI, 2.6–4.5) months. PFS did not differ for patients with co-occurring TP53 mutations (p = 0.937). The DCR at three months was 71 %. Median OS was 8.7 (95 % CI, 1.1–16.4) months. Conclusion: Osimertinib has limited antitumor activity in patients with EGFR exon 20 mutated NSCLC, with an ORR of 5 %.

Additional Metadata
Keywords EGFR exon 20 mutation, Non-small cell lung cancer, Osimertinib
Persistent URL dx.doi.org/10.1016/j.lungcan.2019.12.013, hdl.handle.net/1765/123617
Series VSNU Open Access deal
Journal Lung Cancer
Note corresponding author at Cancer Institute-Antoni van Leeuwenhoek
van Veggel, B. (B.), Madeira R Santos, J.F.V. (J.F. Vilacha), Hashemi, S.M.S. (S. M.S.), Paats, M.S, Monkhorst, K, Heideman, D.A.M, … de Langen, A.J. (A. J.). (2020). Osimertinib treatment for patients with EGFR exon 20 mutation positive non-small cell lung cancer. Lung Cancer, 141, 9–13. doi:10.1016/j.lungcan.2019.12.013