Cancer Res Treat.  2020 Jan;52(1):284-291. 10.4143/crt.2019.200.

Osimertinib in Patients with T790M-Positive Advanced Non-small Cell Lung Cancer: Korean Subgroup Analysis from Phase II Studies

Affiliations
  • 1Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
  • 2Center for Lung Cancer, National Cancer Center, Goyang, Korea
  • 3Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
  • 4Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea
  • 5Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
  • 6Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
  • 7National Taiwan University and National Taiwan University Hospital, Taipei, Taiwan
  • 8Kindai University Faculty of Medicine, Osaka-Sayama, Japan
  • 9Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea

Abstract

Purpose
Osimertinib is a third-generation, irreversible, oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that potently and selectively inhibits both EGFR sensitizing mutation and EGFR T790M and has demonstrated efficacy in non-small cell lung cancer (NSCLC) central nervous system (CNS) metastases. We present results of a subgroup analysis of Korean patients from the pooled data of two global phase II trials: AURA extension (NCT01802632) and AURA2 (NCT02094261).
Materials and Methods
Enrolled patients had EGFR T790M-positive NSCLC and disease progression during or after EGFR-TKI therapy. Patients received osimertinib 80 mg orally once daily until disease progression. The primary endpoint was objective response rate (ORR).
Results
In total, 66 Korean patients received osimertinib treatment with a median treatment duration of 19 months. In the evaluable-for-response population (n=62), ORR was 74% (95% confidence interval [CI], 61.5 to 84.5) and median duration of response was 9.8 months (95% CI, 7.1 to 16.8). In the full analysis set (n=66), median progression-free survival was 10.9 months (95% CI, 8.3 to 15.0; data cutoff November 1, 2016), and median overall survival was 29.2 months (95% CI, 24.8 to 35.7; data cutoff May 1, 2018). Eight patients with CNS metastases were evaluable for response, none of whom showed CNS progression. The most common adverse events were rash (53%), cough (33%), paronychia, diarrhea, and decreased appetite (each 32%).
Conclusion
Efficacy and safety profiles of osimertinib in this subgroup are consistent with the global phase II pooled population, which supports osimertinib as a recommended treatment for Korean patients with T790M positive NSCLC.

Keyword

Non-small-cell lung carcinoma; Tyrosine kinase inhibitor; Epidermal growth factor receptor; South Korea; Clinical trial; Phase II

Figure

  • Fig. 1. Waterfall plot of target lesion size, best percentage change from baseline by blinded independent central review (evaluable-for-response set). Best percentage change in target lesion size is the maximum reduction from baseline or the minimum increase from baseline in the absence of a reduction. Data cutoff November 1, 2016.

  • Fig. 2. Kaplan-Meier analysis of osimertinib 80 mg once daily treatment in Korean patients from AURA extension and AURA 2 studies. (A) Duration of response (DoR) by blinded independent central review (evaluable-for-response set) by study and total. (B) Progression-free survival (PFS) by blinded independent central review (full analysis set) by study and total. Tick marks indicate censored observations. Data cutoff November 1, 2016. CI, confidence interval.


Reference

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