Universität zu Köln

Stratmann, Jan A., Michels, Sebastian, Hornetz, Sofia, Christoph, Daniel C., Sackmann, Sandra, Spengler, Werner, Bischoff, Helge, Schaefer, Monica, Alt, Juergen, Mueller, Annette, Laack, Eckart, Kimmich, Martin, Griesinger, Frank and Sebastian, Martin (2018). Efficacy and safety analysis of the German expanded access program of osimertinib in patients with advanced, T790M-positive non-small cell lung cancer. J. Cancer Res. Clin. Oncol., 144 (12). S. 2457 - 2464. NEW YORK: SPRINGER. ISSN 1432-1335

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Abstract

Purpose Osimertinib, a third-generation irreversible mutant-selective inhibitor of EGFR kinase activity was clinically evaluated in the AURA trials, where it showed high clinical efficacy and a favorable toxicity profile in patients with acquired exon 20-EGFR pT790M mutation. We provide the clinical data of the German expanded access program that further characterizes the efficacy and safety of osimertinib in a heterogeneous patient population outside clinical trials. Methods We performed a retrospective data analysis on patients who were included into the German osimertinib EAP. Results Of 81 patients enrolled, 51 patients (62.9%) with sufficient case report form data were available for efficacy and safety analysis. Unconfirmed overall response rate was 80.0% with 2 patients (3.9%) achieving a complete remission and 37 patients (72.5%) having a partial remission. Disease control rate was 95.9% and only two patients showed refractory disease. Disease control rate did not correlate with clinical characteristics and was independent of number as well as type of the previous therapy line(s). Estimated progression-free survival was 10.1 months (95% CI 9.2-11.0 months). Osimertinib showed a favorable toxicity profile with no dose reductions in our observation period, even in patients with low performance status. Median survival from first diagnosis to data cut-off was 47.3 months (95% CI 43.3-51.9 months). Repeated tissue/liquid biopsy of three patients in our cohort who showed disease progression revealed an amplification of MET. Conclusions We confirm safety and efficacy of osimertinib with high response rates among all subgroups, including patients with poor performance status and multiple prior therapy lines. Amplification of MET might mediate acquired resistance to osimertinib.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Stratmann, Jan A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Michels, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Hornetz, Sofia UNSPECIFIED UNSPECIFIED UNSPECIFIED Christoph, Daniel C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sackmann, Sandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Spengler, Werner UNSPECIFIED UNSPECIFIED UNSPECIFIED Bischoff, Helge UNSPECIFIED UNSPECIFIED UNSPECIFIED Schaefer, Monica UNSPECIFIED UNSPECIFIED UNSPECIFIED Alt, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, Annette UNSPECIFIED UNSPECIFIED UNSPECIFIED Laack, Eckart UNSPECIFIED UNSPECIFIED UNSPECIFIED Kimmich, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Griesinger, Frank UNSPECIFIED UNSPECIFIED UNSPECIFIED Sebastian, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-163951
DOI:	10.1007/s00432-018-2754-x
Journal or Publication Title:	J. Cancer Res. Clin. Oncol.
Volume:	144
Number:	12
Page Range:	S. 2457 - 2464
Date:	2018
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1432-1335
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language 1ST-LINE TREATMENT; OPEN-LABEL; PHASE-III; CHEMOTHERAPY; INHIBITOR; MULTICENTER; RESISTANCE; ERLOTINIB; AZD9291; ADENOCARCINOMA Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/16395