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Efficacy and safety analysis of the German expanded access program of osimertinib in patients with advanced, T790M-positive non-small cell lung cancer

  • Original Article – Clinical Oncology
  • Published:
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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.

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Acknowledgements

This manuscript or its content is not under consideration for publication elsewhere; its publication is approved by all authors and tacitly or explicitly by the responsible authorities where the work was carried out. The sponsor reviewed the final version of the manuscript.

Funding

This work was supported by Astra Zeneca.

Author information

Author notes

  1. Jan A. Stratmann, Sebastian Michels, Frank Griesinger and Martin Sebastian contributed equally to the manuscript.

Authors and Affiliations

  1. Department of Hematology and Oncology, Johann Wolfgang Goethe University Hospital of Frankfurt, Theodor Stern Kai 7, 60596, Frankfurt am Main, Germany

    Jan A. Stratmann, Sofia Hornetz & Martin Sebastian

  2. Department of Hematology and Oncology, Pius Hospital Oldenburg, Georgstraße 12, 26121, Oldenburg, Germany

    Frank Griesinger

  3. Lung Cancer Group Cologne, University Hospital of Cologne, Kerpener Str. 62, 50937, Cologne, Germany

    Sebastian Michels

  4. Department of Medical Oncology, University Hospital of Essen, Hufelandstr. 55, 45147, Essen, Germany

    Daniel C. Christoph

  5. Department of Pneumology, Clinic Bremen-Ost, Züricher Str. 40, 28325, Bremen, Germany

    Sandra Sackmann

  6. Department of Internal Medicine II, University Hospital of Tübingen, Otfried-Müller-Straße 10, 72076, Tübingen, Germany

    Werner Spengler

  7. Department of Thoracic Oncology, University Hospital of Heidelberg, Röntgenstr. 1, 69126, Heidelberg, Germany

    Helge Bischoff

  8. Helios Clinic Emil von Behring, Walterhöferstr. 11, 14165, Berlin, Germany

    Monica Schäfer

  9. Department of Internal Medicine III, Universitätsmedizin Mainz, Langenbeckstr. 1, 55131, Mainz, Germany

    Jürgen Alt

  10. Department of Hematology and Oncology, University Hospital of Mannheim, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany

    Annette Müller

  11. Hämato-Onkologie Hamburg, Stader Straße 203c, 21075, Hamburg, Germany

    Eckart Laack

  12. Department of Pneumology, Clinic Schillerhoehe, Solitudestr. 18, 70839, Gerlingen, Germany

    Martin Kimmich

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  1. Jan A. Stratmann
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Corresponding author

Correspondence to Jan A. Stratmann.

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Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Conflict of interest

JS reports personal fees from Bristol-Myers & Squibb, personal fees from Novartis, outside the submitted work. SM reports grants and personal fees from Novartis, grants and personal fees from Pfizer, personal fees from Boehringer-Ingelheim, outside the submitted work. SH has nothing to disclose. DCC reports personal fees from AstraZeneca, personal fees from Boehringer-Ingelheim, personal fees from Bristol-Myers Squibb, personal fees from Chugai, personal fees from Lilly Eli, personal fees from Merck, Sharp & Dohme, personal fees from Novartis, personal fees from Pfizer, personal fees from Roche, outside the submitted work. SS has nothing to disclose. WS has nothing to disclose. HB has nothing to disclose. MSc has nothing to disclose. JA has nothing to disclose. AM reports personal fees from Boehringer-Ingelheim, personal fees from Roche, personal fees and non-financial support from Novartis, personal fees from Astra Zeneca, personal fees from Merck, non-financial support from Pharma Mar, non-financial support from Celgene, non-financial support from MSD, non-financial support from BMS, outside the submitted work. EL has nothing to disclose. MK has nothing to disclose. MSe reports personal fees from Lilly, personal fees from Astra-Zeneca, personal fees from Bristol-Myers & Squibb, personal fees from Merck Sharp & Dohme, personal fees from Pfizer, personal fees from Takeda, personal fees from Roche, personal fees from AbbVie, personal fees from Boehringer-Ingelheim, personal fees from Celgene, personal fees from Novartis, outside the submitted work.

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Stratmann, J.A., Michels, S., Hornetz, S. et al. 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, 2457–2463 (2018). https://doi.org/10.1007/s00432-018-2754-x

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