B van Veggel1, J F Vilacha Madeira R Santos2, S M S Hashemi3, M S Paats4, K Monkhorst5, D A M Heideman6, M Groves2, T Radonic6, E F Smit1, E Schuuring7, A J van der Wekken8, A J de Langen9. 1. Dept of Thoracic Oncology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, the Netherlands. 2. University of Groningen, Faculty of Science and Engineering, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands. 3. Dept of Pulmonary Diseases, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands. 4. Dept of Pulmonary Diseases, Erasmus Medical Center, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands. 5. Dept of Pathology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, the Netherlands. 6. Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands. 7. Dep of Pathology and Medical Biology, University of Groningen and University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands. 8. Dept of Pulmonary Diseases, University of Groningen and University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands. 9. Dept of Thoracic Oncology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, the Netherlands. Electronic address: j.d.langen@nki.nl.
Abstract
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 %.
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 %.
Authors: James Chih-Hsin Yang; Martin Schuler; Sanjay Popat; Satoru Miura; Keunchil Park; Antonio Passaro; Filippo De Marinis; Flavio Solca; Angela Märten; Edward S Kim Journal: Front Oncol Date: 2022-04-28 Impact factor: 5.738
Authors: Gregory J Riely; Joel W Neal; D Ross Camidge; Alexander I Spira; Zofia Piotrowska; Daniel B Costa; Anne S Tsao; Jyoti D Patel; Shirish M Gadgeel; Lyudmila Bazhenova; Viola W Zhu; Howard L West; Tarek Mekhail; Ryan D Gentzler; Danny Nguyen; Sylvie Vincent; Steven Zhang; Jianchang Lin; Veronica Bunn; Shu Jin; Shuanglian Li; Pasi A Jänne Journal: Cancer Discov Date: 2021-02-25 Impact factor: 39.397
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