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Published on: June 26, 2019
Osimertinib treatment for patients with EGFR exon 20 mutation positive non-small cell lung cancer
B van Veggel1, J F Vilacha Madeira R Santos2, S M S Hashemi3
1Dept of Thoracic Oncology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, the Netherlands.
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 %.
Insights
Osimertinib showed limited effectiveness in non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) exon 20 insertions. The objective response rate was only 5%, indicating minimal antitumor activity in this patient group.
Area of Science:
- Oncology
- Medical Genetics
- Pharmacology
Background:
- Epidermal growth factor receptor (EGFR) exon 20 insertions are a subset of EGFR mutations in non-small cell lung cancer (NSCLC).
- These mutations confer primary resistance to existing EGFR tyrosine kinase inhibitors (TKIs).
- Preclinical data suggested potential activity of osimertinib against EGFR exon 20 insertion mutations.
Purpose of the Study:
- To evaluate the efficacy of osimertinib in advanced stage NSCLC patients with EGFR exon 20 insertion mutations.
- To assess objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).
Main Methods:
- Retrospective analysis of 21 advanced NSCLC patients treated with osimertinib (80 or 160 mg daily).
- Data collected from April 2016 to June 2018 across four Dutch institutions.
- Efficacy outcomes (ORR, PFS, DCR, OS) assessed using RECIST v1.1 criteria.
Main Results:
- The overall objective response rate (ORR) was 5% (1 partial response, 17 stable disease, 3 progressive disease).
- Median progression-free survival (PFS) was 3.6 months.
- Disease control rate (DCR) at three months was 71%, with a median overall survival (OS) of 8.7 months.
Conclusions:
- Osimertinib demonstrates limited antitumor activity in NSCLC patients with EGFR exon 20 insertion mutations.
- The observed ORR of 5% suggests that osimertinib is not highly effective as a monotherapy for this specific mutation type.
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