LBA6_PR - Osimertinib vs standard of care (SoC) EGFR-TKI as first-line treatment in patients with EGFR-TKI sensitising mutation (EGFRm) positive advanced non...

Date 19 November 2017
Event ESMO Asia 2017 Congress
Session Thoracic malignancies 2
Topics Anti-Cancer Agents & Biologic Therapy
Biomarkers
Non-Small-Cell Lung Cancer, Metastatic
Lung and other Thoracic Tumours
Personalised Medicine
Presenter Byoung Chul Cho
Citation Annals of Oncology (2017) 28 (suppl_10): x186-x195. 10.1093/annonc/mdx729
Authors B.C. Cho1, B. Chewaskulyong2, K.H. Lee3, A. Dechaphunkul4, V. Sriuranpong5, F. Imamura6, Y. Ohe7, N. Nogami8, T. Kurata9, I. Okamoto10, C. Zhou11, Y. Cheng12, E.K. Cho13, V.P. Jye14, J. Lee15, H. Mann16, M. Saggese17, T. Reungwetwattana18
  • 1Division Of Medical Oncology, Department Of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, 03722 - Seoul/KR
  • 2Oncology Unit, Department Of Medicine, Chiang Mai University, Chiang Mai/TH
  • 3Division Of Medical Oncology, Chungbuk National University Hospital, 361-711 - Cheongju/KR
  • 4Division Of Medical Oncology, Department Of Internal Medicine, Prince of Songkla University, Songkhla/TH
  • 5Division Of Medical Oncology, Department Of Medicine, Faculty Of Medicine, Chulalongkorn University and the King Chulalongkorn Memorial Hospital, 10330 - Bangkok/TH
  • 6Department Of Thoracic Oncology, Osaka International Cancer Institute, 541-8567 - Osaka/JP
  • 7Department Of Thoracic Oncology, National Cancer Center Hospital, 104-0045 - Tokyo/JP
  • 8Department Of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center, 791-0280 - Matsuyama/JP
  • 9Department Of Thoracic Oncology, Kansai Medical University Hospital, 589-8511 - Osaka/JP
  • 10Research Institute For Diseases Of The Chest, Kyushu University Hospital, Fukuoka/JP
  • 11Department Of Oncology, Shanghai Pulmonary Hospital, Tongji University, 200433 - Shanghai/CN
  • 12Division Of Thoracic Oncology, Jilin Provincial Cancer Hospital, Changchun/CN
  • 13Division Of Hematology And Oncology, Department Of Internal Medicine, Gachon University Gil Medical Center, Incheon/KR
  • 14Radiotherapy And Oncology Department, Hospital Umum Sarawak, Kuching/MY
  • 15Department Of Hematology/oncology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 463-707 - Seongnam/KR
  • 16Biometrics And Information Science, AstraZeneca, Cambridge/GB
  • 17Global Medicines Development, AstraZeneca, Cambridge/GB
  • 18Faculty Of Medicine, Ramathibodi Hospital, Mahidol University, 10400 - Bangkok/TH

Abstract

Background

Osimertinib is a 3rd generation, CNS-active EGFR-TKI that potently and selectively inhibits both EGFRm and EGFR T790M resistance mutations. FLAURA (NCT02296125) is a PhIII, double-blind, randomised study assessing efficacy and safety of osimertinib vs SoC EGFR-TKI in first-line pts with EGFRm advanced NSCLC. We present results of an Asian subset (Asian pts enrolled at Asian sites) of FLAURA.

Methods

Eligible pts: ≥18 yrs (Japan: ≥20 yrs), no prior EGFR-TKI/systemic anti-cancer therapy for advanced disease, with Ex19del/L858R EGFRm advanced NSCLC. Neurologically stable pts with CNS mets were allowed, provided definitive treatment/steroids were completed for ≥2 weeks. Pts were randomised 1:1 to osimertinib 80 mg once daily (qd) orally (po) or SoC EGFR-TKI (gefitinib 250 mg or erlotinib 150 mg qd po), stratified by mutation status (Ex19del/L858R) and race (Asian/non-Asian). Primary endpoint: progression-free survival (PFS) by RECIST v1.1, by investigator. Data cutoff: 12 June 2017.

Results

322 Asian pts (Chinese n = 46, Japanese n = 120, other Asian n = 156) received treatment. Baseline characteristics were generally balanced across arms.

PFS benefit was broadly consistent across predefined subgroups (HR ranging from 0.48–0.68). Median total treatment duration (range): 15.5 (0.5–25.5) mo with osimertinib; 11.7 (0–26.2) with SoC. All causality adverse events (AEs), by investigator: osimertinib, 99% (Gr ≥ 3, 40%); SoC, 99% (Gr ≥ 3, 48%). AEs leading to discontinuation: osimertinib, 15%; SoC, 21%. Most common all causality AEs with osimertinib: diarrhoea (54% [Gr ≥ 3, 2%]), paronychia (40% [1%]); SoC: diarrhoea (54% [3%]), dermatitis acneiform (53% [6%]).

Conclusions

Results in Asian pts with EGFRm advanced NSCLC were consistent with the overall results of the FLAURA study. First-line osimertinib demonstrated superior efficacy over SoC. There were no new safety findings.

Clinical trial identification

NCT02296125

Legal entity responsible for the study

AstraZeneca

Funding

AstraZeneca

Disclosure

B.C. Cho: Research funding: Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST; Consulting role: Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, BMS, Yuhan, Pfizer, Eli Lilly. V. Sriuranpong: Received only clinical trial related support from Astra Zeneca. F. Imamura: Research fund, Honoraria from AstraZeneca. Y. Ohe: Honoraria: AstraZeneca, Chugai, Lilly, Ono, BMS, Daiichi-Sankyo, Nipponkayaku, Boehringer Ingelheim, Bayer, Pfizer, MSD, Taiho Research; Funding: AstraZeneca, Chugai, Lilly, ONO, BMS, Kyorin, Dainippon- Sumitomo, Pfizer, Taiho, Novartis, Merck Serono; Consulting Or Advisory Role: AstraZeneca, Chugai, Lilly, Ono, Novartis. N. Nogami: Meiji Seika Pharma Co., Ltd. AstraZeneca Pfizer Inc. Bristol-Myers Squibb Ono Pharmaceutical Co., Ltd. Kyowa Hakko Kirin Taiho Phamaceutical Co., Ltd. Chugai Pharmaceutical Co., Ltd Eli Lilly Japan Boehringer Ingelheim. T. Kurata: Honoraria; AstraZenaca Research funding; AstraZeneca. I. Okamoto: Grants and personal fees from AstraZeneca, Ono Pharmaceutical, Bristol-Myers Squibb, Chugai Pharmaceutical, Eli Lilly Japan, Taiho Pharmaceutical, Boehringer Ingelheim, and Pfizer Japan. C. Zhou: Lecture honoraria: Eli Lily, AstraZeneca, Roche, Pfizer, Sanofi, Boehringer Ingelheim, Henrui; Ad Board: Roche, Boehringer Ingelheim, AstraZeneca. H. Mann, M. Saggese: Employee of AstraZeneca.

All other authors have declared no conflicts of interest.

Table: LBA6_PR

Efficacy endpointOsimertinibSoC
n = 162n = 160
PFS HR (95% confidence interval)0.54 (0.41, 0.72); p