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

Myung-Ju Ahn, Ji-Youn Han, Dong-Wan Kim, Byoung Chul Cho, Jin-Hyoung Kang, Sang-We Kim, James Chih-Hsin Yang, Tetsuya Mitsudomi, Jong Seok Lee, Myung-Ju Ahn, Ji-Youn Han, Dong-Wan Kim, Byoung Chul Cho, Jin-Hyoung Kang, Sang-We Kim, James Chih-Hsin Yang, Tetsuya Mitsudomi, Jong Seok Lee

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.

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

Conflict of interest statement

Dong-Wan Kim reports personal expenses from Novartis.

Jin-Hyoung Kang reports research funding from AstraZeneca, during the conduct of the study; research funding from CKD, Ono Pharmaceutical, and Johnson & Johnson; advisory board participation for AstraZeneca, Eli Lilly, Merck Sharp & Dohme, and Genexin; honoraria from Roche, Novartis, Merck Sharp & Dohme, Ono Pharmaceutical, and Bristol-Myers Squibb, outside the submitted work.

James Chih-Hsin Yang reports personal fees from Boehringer Ingelheim, Eli Lilly, Bayer, Roche/Genentech, Chugai, Astellas, Merck Sharp & Dohme, Merck Serono, Pfizer, Novartis, Clovis Oncology, Celgene, Merrimack, Yuhan Pharmaceuticals, Bristol-Myers Squibb, Ono Pharmaceuticals, Daiichi Sankyo, Astrazeneca, and Hansoh Pharmaceuticals, outside the submitted work.

Tetsuya Mitsudomi Reports Personal Fees From Astrazeneca, During The Conduct Of The Study; Grants And Personal Fees From Boehringer Ingelheim, Grants And Personal Fees From Chugai, Personal Fees From Roche, Personal Fees From Pfizer, Grants And Personal Fees From Merck Sharp & Dohme, Grants And Personal Fees From Ono Pharmaceutical, Personal Fees From Bristol-myers Squibb, And Grants And Personal Fees From Taiho, Outside The Submitted Work.

The other authors report no conflicts of interest.

Figures

Fig. 1.
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.
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.

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