Osimertinib Improves Progression-free Survival in Asian EGFR-mutated Lung Cancer Patients

LUGANO, Switzerland – Osimertinib improves progression-free survival compared to standard first line therapy in Asian patients with EGFR-mutated non-small-cell lung cancer (NSCLC), according to the Asian subset analysis of the FLAURA trial presented at the ESMO Asia 2017 Congress (1), sumultaneously published in The New England Journal of Medicine. (2)

EGFR mutations occur in 30–40% of NSCLC in Asian populations compared to 10–15% in Western populations. The phase III FLAURA trial compared osimertinib, a third generation EGFR-tyrosine kinase inhibitor (TKI), to standard of care EGFR-TKIs (erlotinib or gefitinib) as first line therapy in NSCLC patients with EGFR mutations. A total of 556 patients from Asia, Europe, and North America were randomised 1:1 to treatment with osimertinib or standard of care. Osimertinib improved progression-free survival by 54%.

This subset analysis included the 322 Asian patients in the FLAURA trial, of whom 46 were Chinese, 120 were Japanese, and 156 were from other parts of Asia.

The median progression-free survival was 16.5 months with osimertinib compared to 11.0 months for the standard therapy, with a hazard ratio of 0.54 (95% confidence interval, 0.41–0.72; p<0.0001).

The median duration of response was two-fold higher for patients treated with osimertinib (17.6 months) compared to standard of care (8.7 months). The overall response rate was 80% with osimertinib compared to 75% with standard of care treatment. Median overall survival was not reached. The incidence of grade 3 or higher toxicities was lower for osimertinib (40%) than the standard treatment (48%).

Lead author Professor Byoung Chul Cho, Yonsei Cancer Center, Seoul, Korea, said: “As in the overall trial population, osimertinib provided a significant progression-free survival benefit in Asian patients with EGFR-mutated NSCLC. Asian patients had similar toxicities with osimertinib as the overall FLAURA population. Osimertinib should be the preferred first line treatment for EGFR-mutant NSCLC in Asia.”

Commenting on the findings Professor James CH Yang, Chairman, Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei City, Taiwan, said: “The results of this subset analysis are quite compatible with the findings in the overall population presented at the ESMO 2017 Congress in Madrid. (3) We can therefore conclude that osimertinib can be considered as the standard of care for the first line treatment of Asian advanced NSCLC patients with EGFR mutations.”

“The proportion of patients having adverse events that caused them to stop taking osimertinib was similar in the overall (13%) and Asian (15%) populations,” added Yang. “We tend to think osimertinib is a well tolerated drug so these discontinuation rates were surprisingly high and need further investigation.”

Yang continued: “Although there was no statistical difference between the hazard ratios for progression-free survival, it was numerically lower in non-Asians (0.34) compared to Asians (0.54). There is an ongoing debate as to whether Asian and non-Asian patients with EGFR mutations have distinct responses to EGFR-TKIs. This might be due to variations in clinical practice rather than biology. A meta-analysis of all relevant studies could shed light on this issue.”

“It will also be important to know whether Asian and non-Asian patients in the FLAURA trial with brain metastases had similar outcomes,” said Yang.(4)

-END-

Notes to Editors

Please make sure to use the official name of the meeting in your reports: ESMO Asia 2017 Congress

References

1. Abstract 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-small cell lung cancer (NSCLC): FLAURA Asian subset‘ will be presented by Byoung Chul Cho during the Mini Oral session Thoracic malignancies 2 on Sunday, 19 November 2017, 14:30 to 15:25 (SGT) in Room 310. Annals of Oncology, Volume 28, 2017 Supplement 10
2. ‘Osimertinib in treatment-naïve EGFR mutation-positive advanced NSCLC (FLAURA)’ S Ramalingam et al, The New England Journal of Medicine (NEJM), 10.1056/NEJMoa1713137, http://www.nejm.org/doi/full/10.1056/NEJMoa1713137
3. Abstract LBA2_PR ‘Osimertinib vs SoC EGFR-TKI as first-line treatment in patients with EGFRm advanced NSCLC (FLAURA)’ S. Ramalingam et al. Annals of Oncology, Volume 28, 2017 Supplement
4. Abstract LBA5 ‘CNS response to osimertinib vs standard of care (SoC) EGFR-TKI as first-line therapy in patients (pts) with EGFR-TKI sensitising mutation (EGFRm)-positive advanced non-small cell lung cancer (NSCLC): data from the FLAURA study’ will be presented by Johan Vansteenkiste during the Proffered paper session 1 on Saturday, 18 November 2017, 08:30 to 10:30 (SGT) in Hall 405. Annals of Oncology, Volume 28, 2017 Supplement 10

About the European Society for Medical Oncology (ESMO)

ESMO is the leading professional organisation for medical oncology. With 17,000 members representing oncology professionals from 150 countries worldwide, ESMO is the society of reference for oncology education and information. We are committed to supporting our members to develop and advance in a fast-evolving professional environment.

Abstract LBA 6_PR 

Osimertinib vs standard of care (SoC) EGFR-TKI as first-line treatment in patients with EGFR-TKI sensitising mutation (EGFRm) positive advanced non-small cell lung cancer (NSCLC): FLAURA Asian subset

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.-S. Lee¹⁵, H. Mann¹⁶, M. Saggese¹⁷, T. Reungwetwattana^18 
1Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea, ²Oncology Unit, Department of Medicine, Chiang Mai University, Chiang Mai, Thailand, ³Division of Medical Oncology, Chungbuk National University Hospital, Cheongju, Republic of Korea, ⁴Division of Medical Oncology, Department of Internal Medicine, Prince of Songkla University, Songkhla, Thailand, ⁵Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and the King Chulalongkorn Memorial Hospital, Bangkok, Thailand, ⁶Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan, ⁷Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan, ⁸Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan, ⁹Department of Thoracic Oncology, Kansai Medical University Hospital, Osaka, Japan, ¹⁰Research Institute for Diseases of the Chest, Kyushu University Hospital, Fukuoka, Japan, ¹¹Department of Oncology, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China, ¹²Division of Thoracic Oncology, Jilin Provincial Cancer Hospital, Changchun, China, ¹³Division of Hematology and Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Republic of Korea, ¹⁴Radiotherapy and Oncology Department, Hospital Umum Sarawak, Kuching, Malaysia, ¹⁵Department of Hematology/Oncology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea, ¹⁶Biometrics and Information Science, AstraZeneca, Cambridge, UK, ¹⁷Global Medicines Development, AstraZeneca, Cambridge, UK, ¹⁸Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

Background: Osimertinib is a 3^rd 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. 

DoR, duration of response; HR, hazard ratio; mo, month; NC, not calculable; ORR, objective response rate; OS, overall survival; PFS, progression-free survival * Median PFS with 95% confidence intervals calculated from Kaplan Meier method. ^† A HR ˂1 favours osimertinib.

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.

Keywords: osimertinib, EGFR-TKI, non-small cell lung cancer (NSCLC), first-line treatment