AZD9291 Versus Gefitinib or Erlotinib in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer (FLAURA)

A Phase III, Double-blind, Randomised Study to Assess the Safety and Efficacy of AZD9291 Versus a Standard of Care Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor as First Line Treatment in Patients With Epidermal Growth Factor Receptor Mutation Positive, Locally Advanced or Metastatic Non Small Cell Lung Cancer.

To assess the efficacy and safety of AZD9291 versus a standard of care epidermal growth factor receptor tyrosine kinase inhibitor in patients with locally advanced or Metastatic Non Small Cell Lung Cancer

Study Overview

• Status: Active, not recruiting
• Conditions: Locally Advanced or Metastatic EGFR Sensitising Mutation Positive Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: AZD9291 80 mg/40 mg + placebo; Drug: Placebo Erlotinib 150/100mg; Drug: Placebo Gefitinib 250 mg; Drug: Erlotinib 150/100 mg; Drug: Gefitinib 250 mg; Drug: Placebo AZD9291 80 mg/ 40 mg

Detailed Description

This is a Phase III, double-blind, randomised study assessing the efficacy and safety of AZD9291 (80 mg orally, once daily) versus a standard of care (SoC) Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor (TKI) (either gefitinib [250 mg orally, once daily] or erlotinib [150 mg orally, once daily]) in patients with locally advanced or metastatic Non-small Cell Lung Cancer (NSCLC) that is known to be EGFR sensitising mutation (EGFRm) positive, treatment-naïve and eligible for first-line treatment with an EGFR-TKI.

• Study Type: Interventional
• Enrollment (Actual): 674
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Camperdown, Australia, 2050
    • Research Site
  • Chermside, Australia, 4032
    • Research Site
  • Clayton, Australia, 3168
    • Research Site
  • Heidelberg, Australia, 3084
    • Research Site
  • Kogarah, Australia, 2217
    • Research Site
  • Nedlands, Australia, 6009
    • Research Site
  • Woolloongabba, Australia, 4102
    • Research Site
• Belgium
  • Leuven, Belgium, 3000
    • Research Site
  • Liège, Belgium, 4000
    • Research Site
  • Roeselare, Belgium, 8800
    • Research Site
• Brazil
  • Porto Alegre, Brazil, 90610-000
    • Research Site
• Bulgaria
  • Sofia, Bulgaria, 1330
    • Research Site
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Research Site
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Research Site
    • Ottawa, Ontario, Canada, K1H 8L6
      • Research Site
    • Toronto, Ontario, Canada, M5G 2M9
      • Research Site
    • Toronto, Ontario, Canada, M4N 3M5
      • Research Site
    • Toronto, Ontario, Canada, M5G 1X5
      • Research Site
• China
  • Beijing, China, 100071
    • Research Site
  • Beijing, China, 100853
    • Research Site
  • Changchun, China, 130012
    • Research Site
  • Changchun, China, 130021
    • Research Site
  • Chongqing, China, 400038
    • Research Site
  • Chongqing, China, 400042
    • Research Site
  • Chongqing, China, 400037
    • Research Site
  • Fuzhou, China, 350025
    • Research Site
  • Guangzhou, China, 510080
    • Research Site
  • Hangzhou, China, 310022
    • Research Site
  • Nanjing, China, 210029
    • Research Site
  • Nanning, China, 530021
    • Research Site
  • Shanghai, China, 200433
    • Research Site
  • Shenyang, China, 110001
    • Research Site
  • Suzhou, China, 215006
    • Research Site
  • Wuhan, China, 430071
    • Research Site
  • Xi'an, China, 710061
    • Research Site
  • Xi'an, China, 710038
    • Research Site
  • Yangzhou, China, 225001
    • Research Site
  • Ürümqi, China, 830000
    • Research Site
• Czechia
  • Ostrava, Czechia, 708 52
    • Research Site
• France
  • Caen, France, F-14033
    • Research Site
  • Creteil, France, 94010
    • Research Site
  • Lyon Cedex 08, France, 69373
    • Research Site
  • Nantes, France, 44202
    • Research Site
  • Toulon Naval, France, 83800
    • Research Site
  • Villejuif, France, 94805
    • Research Site
• Germany
  • Bad Berka, Germany, 99437
    • Research Site
  • Berlin, Germany, 13125
    • Research Site
  • Gauting, Germany, 82131
    • Research Site
  • Halle, Germany, 06120
    • Research Site
  • Heidelberg, Germany, 69126
    • Research Site
  • Karlsruhe, Germany, 76137
    • Research Site
  • Lübeck, Germany, 23538
    • Research Site
  • München, Germany, 81925
    • Research Site
  • Villingen-Schwenningen, Germany, 78052
    • Research Site
• Hungary
  • Farkasgyepü, Hungary, 8582
    • Research Site
  • Gyöngyös - Mátraháza, Hungary, 3200
    • Research Site
  • Miskolc, Hungary, 3529
    • Research Site
  • Székesfehérvár, Hungary, 8000
    • Research Site
  • Tatabánya, Hungary, 2800
    • Research Site
  • Zalaegerszeg, Hungary, 8900
    • Research Site
• Israel
  • Haifa, Israel, 31999
    • Research Site
  • Kfar-Saba, Israel, 4428164
    • Research Site
  • Petach Tikva, Israel, 49100
    • Research Site
  • Tel Hashomer, Israel, 52621
    • Research Site
• Italy
  • Cremona, Italy, 26100
    • Research Site
  • Lecce, Italy, 73100
    • Research Site
  • Lecco, Italy, 23900
    • Research Site
  • Orbassano, Italy, 10043
    • Research Site
  • Parma, Italy, 43126
    • Research Site
  • Roma, Italy, 00144
    • Research Site
  • Sondrio, Italy, 23100
    • Research Site
  • Terni, Italy, 05100
    • Research Site
• Japan
  • Chuo-ku, Japan, 104-0045
    • Research Site
  • Fukuoka-shi, Japan, 812-8582
    • Research Site
  • Hirakata-shi, Japan, 573-1191
    • Research Site
  • Kanazawa-shi, Japan, 920-8641
    • Research Site
  • Kashiwa, Japan, 277-8577
    • Research Site
  • Kobe-shi, Japan, 650-0047
    • Research Site
  • Matsuyama-shi, Japan, 791-0280
    • Research Site
  • Natori-shi, Japan, 981-1293
    • Research Site
  • Osaka-shi, Japan, 541-8567
    • Research Site
  • Osakasayama-shi, Japan, 589-8511
    • Research Site
  • Sagamihara-shi, Japan, 252-0375
    • Research Site
  • Sakai-shi, Japan, 591-8555
    • Research Site
  • Sendai-shi, Japan, 980-0873
    • Research Site
  • Sunto-gun, Japan, 411-8777
    • Research Site
  • Yokohama-shi, Japan, 241-8515
    • Research Site
  • Yokohama-shi, Japan, 232-0024
    • Research Site
  • Yokohama-shi, Japan, 240-8555
    • Research Site
  • Yokohama-shi, Japan, 236-0051
    • Research Site
• Korea, Republic of
  • Cheongju-si, Korea, Republic of, 28644
    • Research Site
  • Incheon, Korea, Republic of, 405-760
    • Research Site
  • Seongnam-si, Korea, Republic of, 13620
    • Research Site
  • Seoul, Korea, Republic of, 03722
    • Research Site
  • Seoul, Korea, Republic of, 02841
    • Research Site
  • Seoul, Korea, Republic of, 06591
    • Research Site
  • Seoul, Korea, Republic of, 5030
    • Research Site
• Malaysia
  • Kuala Lumpur, Malaysia, 59100
    • Research Site
  • Kuantan, Malaysia, 25100
    • Research Site
  • Kuching, Malaysia, 93586
    • Research Site
• Philippines
  • Cebu, Philippines, 6000
    • Research Site
  • Manila, Philippines, 1000
    • Research Site
  • Quezon City, Philippines, 1100
    • Research Site
• Poland
  • Brzozoów, Poland, 36-200
    • Research Site
  • Otwock, Poland, 05-400
    • Research Site
  • Poznań, Poland, 60-569
    • Research Site
  • Szczecin, Poland, 70-891
    • Research Site
  • Warszawa, Poland, 02-781
    • Research Site
• Portugal
  • Amadora, Portugal, 2720-276
    • Research Site
  • Lisboa, Portugal, 1769-001
    • Research Site
  • Porto, Portugal, 4200-072
    • Research Site
  • Vila Nova de Gaia, Portugal, 4434-502
    • Research Site
• Romania
  • Bucharest, Romania, 050098
    • Research Site
  • Bucuresti, Romania, 022328
    • Research Site
  • Craiova, Romania, 200347
    • Research Site
• Russian Federation
  • Saint Petersburg, Russian Federation, 198255
    • Research Site
  • Saint Petersburg, Russian Federation, 197022
    • Research Site
  • Saint Petersburg, Russian Federation, 197758
    • Research Site
• Spain
  • Barcelona, Spain, 08041
    • Research Site
  • Barcelona, Spain, 08907
    • Research Site
  • Barcelona, Spain, 08221
    • Research Site
  • Coruña, Spain, 15006
    • Research Site
  • Lugo, Spain, 27003
    • Research Site
  • Lérida, Spain, 25198
    • Research Site
  • Madrid, Spain, 28040
    • Research Site
  • Málaga, Spain, 29010
    • Research Site
  • Sevilla, Spain, 41014
    • Research Site
  • Zaragoza, Spain, 50009
    • Research Site
• Sweden
  • Linköping, Sweden, 581 85
    • Research Site
• Switzerland
  • Luzern, Switzerland, 6000
    • Research Site
  • Winterthur, Switzerland, 8401
    • Research Site
  • Zürich, Switzerland, 8091
    • Research Site
• Taiwan
  • Kaohsiung, Taiwan, 833
    • Research Site
  • Taichung City, Taiwan, 402
    • Research Site
  • Tainan, Taiwan, 704
    • Research Site
  • Tainan City, Taiwan, 73657
    • Research Site
  • Taoyuan City, Taiwan, 333
    • Research Site
• Thailand
  • Bangkok, Thailand, 10330
    • Research Site
  • Bangkok, Thailand, 10400
    • Research Site
  • Bangkok, Thailand, 10700
    • Research Site
  • Hat Yai, Thailand, 90110
    • Research Site
  • Muang, Thailand, 50200
    • Research Site
• Turkey
  • Ankara, Turkey, 6500
    • Research Site
  • Istanbul, Turkey, 34069
    • Research Site
  • Izmir, Turkey, 35100
    • Research Site
• Ukraine
  • Dnipro, Ukraine, 49102
    • Research Site
  • Kryvyi Rih, Ukraine, 50048
    • Research Site
  • Lviv, Ukraine, 79031
    • Research Site
  • Sumy, Ukraine, 40022
    • Research Site
• United Kingdom
  • London, United Kingdom, NW1 2BU
    • Research Site
  • Maidstone, United Kingdom, ME16 9QQ
    • Research Site
  • Withington, United Kingdom, M20 4BX
    • Research Site
• United States
  • California
    • Anaheim, California, United States, 92801
      • Research Site
    • Santa Rosa, California, United States, 95403
      • Research Site
    • West Hills, California, United States, 91307
      • Research Site
  • Florida
    • Tampa, Florida, United States, 33612
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Research Site
    • Atlanta, Georgia, United States, 30322
      • Research Site
    • Marietta, Georgia, United States, 30060
      • Research Site
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Research Site
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Research Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Research Site
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Research Site
  • North Carolina
    • Salisbury, North Carolina, United States, 28144
      • Research Site
  • Vermont
    • Burlington, Vermont, United States, 05401
      • Research Site
• Vietnam
  • Hanoi, Vietnam, 100000
    • Research Site
  • Hanoi, Vietnam, 10000
    • Research Site
  • Ho Chi Minh City, Vietnam, 70000
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female, aged at least 18 years.
2. Pathologically confirmed adenocarcinoma of the lung.
3. Locally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy.
4. The tumour harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R).
5. Mandatory provision of an unstained, archived tumour tissue sample in a quantity sufficient to allow for central analysis of EGFR mutation status.
6. Patients must be treatment-naïve for locally advanced or metastatic NSCLC and eligible to receive first-line treatment with gefitinib or erlotinib as selected by the participating centre. Prior adjuvant and neo-adjuvant therapy is permitted(chemotherapy, radiotherapy, investigational agents).
7. Provision of informed consent prior to any study specific procedures, sampling, and analysis.
8. World Health Organization Performance Status of 0 to 1 with no clinically significant deterioration over the previous 2 weeks and a minimum life expectancy of 12 weeks

Exclusion Criteria:

1. Treatment with any of the following:

   • Prior treatment with any systemic anti-cancer therapy for locally advanced/metastatic NSCLC.
   • Prior treatment with an EGFR-TKI.
   • Major surgery within 4 weeks of the first dose of study drug.
   • Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug.
   • Patients currently receiving medications or herbal supplements known to be potent inducers of cytochrome P450 (CYP) 3A4.
   • Alternative anti-cancer treatment
   • Treatment with an investigational drug within five half-lives of the compound or any of its related material.
2. Any concurrent and/or other active malignancy that has required treatment within 2 years of first dose of study drug.
3. Spinal cord compression, symptomatic and unstable brain metastases, except for those patients who have completed definitive therapy, are not on steroids, have a stable neurologic status for at least 2 weeks after completion of the definitive therapy and steroids.
4. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses; or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV).
5. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of AZD9291.

6. Any of the following cardiac criteria:

   • Mean resting corrected QT interval (QTc) >470 msec, obtained from 3 ECGs, using the screening clinic ECG machine-derived QTcF value.
   • Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG.
   • Any patient with any factors that increase the risk of QTc prolongation or risk of arrhythmic events or unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval.
7. Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
8. Involvement in the planning and/or conduct of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AZD9291+ placebo; AZD9291 (80 mg or 40 mg orally, once daily) plus placebo Erlotinib (150mg or 100mg orally, once daily) or placebo Gefitinib (250 mg orally, once daily), in accordance with the randomization schedule.	Drug: AZD9291 80 mg/40 mg + placebo; The initial dose of AZD9291 80 mg once daily can be reduced to 40 mg once daily under specific circumstances. A cycle of treatment is defined as 21 days of once daily treatment. Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.; Drug: Placebo Erlotinib 150/100mg; The initial dose of Placebo Erlotinib 150 mg once daily can be reduced to Placebo 100 mg once daily under specific circumstances. A cycle of treatment is defined as 21 days of once daily treatment. Number of cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.; Other Names: Placebo Tarceva 150/100 mg; Drug: Placebo Gefitinib 250 mg; The initial dose of Placebo Gefitinib 250 mg once daily cannot be reduced. A cycle of treatment is defined as 21 days of once daily treatment. Number of cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.; Other Names: Placebo Iressa 250 mg
Active Comparator: Standard of Care + placebo AZD9291; Erlotinib (150 mg or 100 mg orally, once daily) or placebo Gefitinib (250 mg orally, once daily) plus placebo AZD9291 (80 mg or 40 mg orally, once daily), in accordance with the randomisation schedule. Following objective disease progression according to RECIST 1.1, as per investigator assessment, patients who were randomized to Standard of Care arm may have the option to receive open-label AZD9291 (crossover to active AZD9291).	Drug: Erlotinib 150/100 mg; The initial dose of Erlotinib 150mg once daily can be reduced to 10 mg once daily under specific circumstances. A cycle of treatment is defined as 21 days of once daily treatment. Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria. Following objective disease progression according to RECIST 1.1, as per investigator assessment, patients who were randomized to Standard of Care arm may have the option to receive open-label AZD9291 (crossover to active AZD9291).; Other Names: Tarceva 150/100 mg; Drug: Gefitinib 250 mg; The initial dose of Gefitinib 250mg once daily cannot be reduced. A cycle of treatment is defined as 21 days of once daily treatment. Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria. Following objective disease progression according to RECIST 1.1, as per investigator assessment, patients who were randomized to Standard of Care arm may have the option to receive open-label AZD9291 (crossover to active AZD9291).; Other Names: Iressa 250mg; Drug: Placebo AZD9291 80 mg/ 40 mg; The initial dose of Placebo AZD9291 80 mg once daily can be reduced to Placebo AZD9291 40 mg once daily under specific circumstances. A cycle of treatment is defined as 21 days of once daily treatment. Number of cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Progression Free Survival (PFS) (Months)	Progression-free survival was defined as the time from randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdrew from randomized therapy or received another anti-cancer therapy prior to progression and was used to assess the efficacy of single agent osimertinib compared with SoC EGFR-TKI therapy as measured by PFS. The primary endpoint of PFS was based on Investigator assessment.	At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomisation until progression
Percentage of Participants in Progression Free Survival at 6, 12, and 18 Months	Progression-free survival was defined as the time from randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdrew from randomized therapy or received another anti-cancer therapy prior to progression and was used to assess the efficacy of single agent osimertinib compared with SoC EGFR-TKI therapy as measured by PFS.	At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomisation until progression

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR was defined as the number (%) of participants with measurable disease with at least 1 visit response of Complete response (CR) or Partial response (PR) and it was used to further assess the efficacy of osimertinib compared with SoC EGFR-TKI therapy. ORR was based on Investigator assessment.	At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomisation until progression
Duration of Response (DoR)	Duration of response was defined as the time from the date of first documented response until the date of documented progression or death in the absence of disease progression and was used to further assess the efficacy of osimertinib compared with SoC EGFR-TKI therapy.	At baseline and every 6 weeks for the first 18 months and then every 12 weeks until objective disease progression
Disease Control Rate (DCR)	The DCR was defined as the percentage of participants who had a best overall response (BOR) of Complete response (CR), Partial response (PR) or Stable disease (SD) ≥6 weeks prior to any Progressive disease (PD) event and was used to further assess the efficacy of osimertinib compared with SoC EGFR-TKI therapy.	At baseline and every 6 weeks for the first 18 months and then every 12 weeks until objective disease progression
Depth of Response	The Depth of response was defined as the relative change in the sum of the longest diameters of Response Evaluation Criteria in Solid Tumors (RECIST) Target lesions (TLs) at the nadir, in the absence of new lesions (NLs) or progression of Non-target lesions (NTLs), compared to baseline and was used to further assess the efficacy of osimertinib compared with SoC EGFR-TKI therapy	At baseline and every 6 weeks for the first 18 months and then every 12 weeks until objective disease progression
Overall Survival (OS)- Number of Participants With an Event	Overall survival was defined as the time from the date of randomisation until death from any cause and was used to further assess the efficacy of osimertinib compared with SoC EGFR-TKI therapy	From first dose to end of study or date of death from any cause, whichever comes first, assessed every 6 weeks (approximately 29 months)
Plasma Concentrations of AZD9291	To characterise the pharmacokinetics (PK) of osimertinib	Blood samples collected from each participant at pre-dose, 0.5 to 2 hours, and 3 to 5 hours post-dose on Day 1 Cycle 1, and every other cycle thereafter up to and including Cycle 13 (approximately 9 months)
Plasma Concentrations of Metabolites AZ5104	To characterise the pharmacokinetics (PK) of osimertinib metabolite AZ5104.	Blood samples collected from each participant at pre-dose, 0.5 to 2 hours, and 3 to 5 hours post-dose on Day 1 Cycle 1, and every other cycle thereafter up to and including Cycle 13 (approximately 9 months)
Plasma Concentrations of Metabolite AZ7550	To characterise the pharmacokinetics (PK) of osimertinib metabolite AZ7550.	Blood samples collected from each participant at pre-dose, 0.5 to 2 hours, and 3 to 5 hours post-dose on Day 1 Cycle 1, and every other cycle thereafter up to and including Cycle 13 (approximately 9 months)
Participants Reported Outcome by Cancer Therapy Satisfaction Questionnaire 16 Items (CTSQ-16 Questionnaire)	The CTSQ-16 was a 16-item questionnaire measuring 3 domains related to participant's satisfaction with cancer therapy: Expectations of therapy, Feelings about side effects, and Satisfaction with therapy. Scores ranged from 0 to 100 for each domain, with a higher score associated with the best outcome on each domain. The three domains of interest were separately analysed using an ANCOVA stratified by race (Asian versus Non-Asian) and mutation type (Ex19del versus L858R). The results of the analyses were presented in terms of mean together with standard deviation.	Questionnaire completed in cycle 2 and 3, prior to Week 6 scan (approximately 2 months)
Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13)	The EORTC QLQ-LC13 was a lung-cancer-specific module comprising 13 questions to assess lung cancer symptoms (cough, haemoptysis, dyspnoea, and site-specific pain); treatment related side-effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia); and pain medication. An outcome variable consisting of a score from 0 to 100 was derived for each of the symptom scales/symptom items. Higher scores on the global health status/QoL and functioning scales indicated better health status/QoL and function. Higher scores on the symptoms scales indicated greater symptom burden. The analysis was performed using a Mixed-effects model for repeated measures analysis on the change from baseline in PRO symptom score at each visit up to 9 months (281 days), including participants, treatment, visit and treatment by visit interaction as explanatory variables, the baseline PRO score as a covariate along with the baseline PRO score by visit interaction, using an unstructured covariance structure.	Questionnaires completed at baseline, first 9 months, and at week 1, 2, 3, 4, 5, 6, 12, 18, 24, 30 and 36
Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30)	The EORTC QLQ-C30 cancer-specific questionnaire consisted of 30 questions, combined to produce 5 functional scales, 3 symptom scales, 6 individual items, and a global measure of health status/QoL. An outcome variable consisting of a score from 0 to 100 was derived for each of the symptom scales/symptom items, the functional scales, and the global health status/QoL scale in the EORTC QLQ-C30. Higher scores on the global health status and functioning scales indicated better health status/function. Higher scores on the symptoms scales indicated greater symptom burden. The analysis was performed using a Mixed-effects model for repeated measures analysis on the change from baseline in PRO symptom score at each visit up to 9 months (281 days), including participants, treatment, visit and treatment by visit interaction as explanatory variables, the baseline PRO score as a covariate along with the baseline PRO score by visit interaction, using an unstructured covariance structure.	Questionnaires completed at baseline, first 9 months, and at week 6, 12, 18, 24, 30, and 36.

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Parexel

Publications and helpful links

General Publications

• Walding A, Skaltsa K, Casamayor M, Ryden A. Time to deterioration of patient-reported outcomes in non-small cell lung cancer: exploring different definitions. Qual Life Res. 2022 Aug;31(8):2535-2543. doi: 10.1007/s11136-022-03088-0. Epub 2022 Jan 31. Erratum In: Qual Life Res. 2022 Mar 24;:
• Cheng Y, He Y, Li W, Zhang HL, Zhou Q, Wang B, Liu C, Walding A, Saggese M, Huang X, Fan M, Wang J, Ramalingam SS. Osimertinib Versus Comparator EGFR TKI as First-Line Treatment for EGFR-Mutated Advanced NSCLC: FLAURA China, A Randomized Study. Target Oncol. 2021 Mar;16(2):165-176. doi: 10.1007/s11523-021-00794-6. Epub 2021 Feb 5.
• Leighl NB, Karaseva N, Nakagawa K, Cho BC, Gray JE, Hovey T, Walding A, Ryden A, Novello S. Patient-reported outcomes from FLAURA: Osimertinib versus erlotinib or gefitinib in patients with EGFR-mutated advanced non-small-cell lung cancer. Eur J Cancer. 2020 Jan;125:49-57. doi: 10.1016/j.ejca.2019.11.006. Epub 2019 Dec 12.
• Ramalingam SS, Vansteenkiste J, Planchard D, Cho BC, Gray JE, Ohe Y, Zhou C, Reungwetwattana T, Cheng Y, Chewaskulyong B, Shah R, Cobo M, Lee KH, Cheema P, Tiseo M, John T, Lin MC, Imamura F, Kurata T, Todd A, Hodge R, Saggese M, Rukazenkov Y, Soria JC; FLAURA Investigators. Overall Survival with Osimertinib in Untreated, EGFR-Mutated Advanced NSCLC. N Engl J Med. 2020 Jan 2;382(1):41-50. doi: 10.1056/NEJMoa1913662. Epub 2019 Nov 21.
• Brown H, Vansteenkiste J, Nakagawa K, Cobo M, John T, Barker C, Kohlmann A, Todd A, Saggese M, Chmielecki J, Markovets A, Scott M, Ramalingam SS. Programmed Cell Death Ligand 1 Expression in Untreated EGFR Mutated Advanced NSCLC and Response to Osimertinib Versus Comparator in FLAURA. J Thorac Oncol. 2020 Jan;15(1):138-143. doi: 10.1016/j.jtho.2019.09.009. Epub 2019 Oct 9.
• Gray JE, Okamoto I, Sriuranpong V, Vansteenkiste J, Imamura F, Lee JS, Pang YK, Cobo M, Kasahara K, Cheng Y, Nogami N, Cho EK, Su WC, Zhang G, Huang X, Li-Sucholeiki X, Lentrichia B, Dearden S, Jenkins S, Saggese M, Rukazenkov Y, Ramalingam SS. Tissue and Plasma EGFR Mutation Analysis in the FLAURA Trial: Osimertinib versus Comparator EGFR Tyrosine Kinase Inhibitor as First-Line Treatment in Patients with EGFR-Mutated Advanced Non-Small Cell Lung Cancer. Clin Cancer Res. 2019 Nov 15;25(22):6644-6652. doi: 10.1158/1078-0432.CCR-19-1126. Epub 2019 Aug 22.
• Planchard D, Boyer MJ, Lee JS, Dechaphunkul A, Cheema PK, Takahashi T, Gray JE, Tiseo M, Ramalingam SS, Todd A, McKeown A, Rukazenkov Y, Ohe Y. Postprogression Outcomes for Osimertinib versus Standard-of-Care EGFR-TKI in Patients with Previously Untreated EGFR-mutated Advanced Non-Small Cell Lung Cancer. Clin Cancer Res. 2019 Apr 1;25(7):2058-2063. doi: 10.1158/1078-0432.CCR-18-3325. Epub 2019 Jan 18.
• Ohe Y, Imamura F, Nogami N, Okamoto I, Kurata T, Kato T, Sugawara S, Ramalingam SS, Uchida H, Hodge R, Vowler SL, Walding A, Nakagawa K. Osimertinib versus standard-of-care EGFR-TKI as first-line treatment for EGFRm advanced NSCLC: FLAURA Japanese subset. Jpn J Clin Oncol. 2019 Jan 1;49(1):29-36. doi: 10.1093/jjco/hyy179.
• Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH, Dechaphunkul A, Imamura F, Nogami N, Kurata T, Okamoto I, Zhou C, Cho BC, Cheng Y, Cho EK, Voon PJ, Planchard D, Su WC, Gray JE, Lee SM, Hodge R, Marotti M, Rukazenkov Y, Ramalingam SS; FLAURA Investigators. Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. N Engl J Med. 2018 Jan 11;378(2):113-125. doi: 10.1056/NEJMoa1713137. Epub 2017 Nov 18.

Helpful Links

• Cancer
• Lung Cancer
• EGFR mutation
• Erlotinib
• FDA Drug and Device Resources
• Gefitinib
• Related Info
• Clinical Study Protocol
• SAP

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2014
• Primary Completion (Actual): June 19, 2017
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: October 22, 2014
• First Submitted That Met QC Criteria: November 18, 2014
• First Posted (Estimated): November 20, 2014

Study Record Updates

• Last Update Posted (Estimated): January 18, 2024
• Last Update Submitted That Met QC Criteria: January 15, 2024
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Advanced Non-Small Cell Lung Cancer; EGFRm+; AZD9291; TKI; Phase III
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Erlotinib Hydrochloride; Gefitinib; Osimertinib
• Other Study ID Numbers: D5160C00007; 2014-002694-11 (EudraCT Number); U1111-1160-2242 (Other Grant/Funding Number: 112455)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP