A Study of Erlotinib (Tarceva) Versus Gemcitabine/Cisplatin as First-line Treatment in Patients With Non-small Cell Lung Cancer With EGFR Mutations

A Multicenter, Open-label, Randomized Phase III Study to Evaluate the Efficacy and Safety of Erlotinib (Tarceva®) Versus Gemcitabine/Cisplatin as the First-line Treatment for Stage IIIB/IV Non-small Cell Lung Cancer (NSCLC) Patients With Mutations in the Tyrosine Kinase Domain of Epidermal Growth Factor Receptor (EGFR) in Their Tumors

This open-label, randomized, parallel arm study assessed the efficacy and safety of Tarceva (erlotinib) versus gemcitabine/cisplatin combination chemotherapy as first-line treatment in patients with stage IIIB/IV non-small cell lung cancer with epidermal growth factor receptor (EGFR) mutations in their tumours. Patients were randomized to receive either Tarceva 150 mg orally daily or 3-week cycles of gemcitabine 1250 mg/m^2 intravenously (iv) on Days 1 and 8 plus cisplatin 75 mg/m^2 iv on Day 1.

Study Overview

• Status: Completed
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Erlotinib; Drug: Chemotherapy

• Study Type: Interventional
• Enrollment (Actual): 217
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 101149
  • Beijing, China, 100071
  • Changchun, China, 130012
  • ChongQing, China, 400042
  • Chongqing, China, 400038
  • Fuzhou, China, 350014
  • Guangzhou, China, 510080
  • Hangzhou, China, 310016
  • Nanjing, China, 210002
  • Shanghai, China, 200032
  • Shanghai, China, 200433
  • Shanghai, China, 200030
  • Shantou, China, 515041
  • Wuhan, China, 430023
  • Xi'an, China, 710061
• Malaysia
  • Kelantan, Malaysia, 16150
  • Kuala Lumpur, Malaysia, 59100
  • Kuala Lumpur, Malaysia, 50603
  • Nilai, Malaysia, 71800
  • Pahang, Malaysia, 25100
  • Petaling Jaya, Malaysia, 46150
  • Petaling Jaya, Selangor, Malaysia, 46050
  • Pulau Pinang, Malaysia, 11600
• Philippines
  • Davao, Philippines, 8000
  • Desmarinas City, Philippines, 4114
  • Manila, Philippines, 1000
  • Quezon City, Philippines, 1104
  • San Juan, Philippines, 1500

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult participants, ≥ 18 years of age.
• Locally advanced or recurrent (stage IIIB) or metastatic (stage IV) non-small cell lung cancer.
• Presence of epidermal growth factor receptor (EGFR) mutations in tumours.
• Measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 criteria.
• European Cooperative Oncology Group (ECOG) performance status ≤ 2.

Exclusion Criteria:

• Prior exposure to agents directed at the human epidermal receptor (HER) axis (eg, but not limited to erlotinib, gefitinib, cetuximab, or trastuzumab).
• Prior chemotherapy or systemic anti-neoplastic therapy for advanced disease.
• Lack of physical integrity of the upper gastrointestinal tract, or malabsorption syndrome, or inability to take oral medication, or active gastroduodenal ulcer disease.
• Any inflammatory changes of the surface of the eye.
• ≥ Grade 2 peripheral neuropathy.
• History of any other malignancies within 5 years, except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer.
• Brain metastasis or spinal cord compression that has not yet been definitely treated with surgery and/or radiation, or treated but without evidence of stable disease for at least 2 months.
• Human immunodeficiency virus (HIV) infection.
• Pregnant, nursing, or lactating women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Erlotinib; Participants received erlotinib 150 mg orally once daily until progressive disease or unacceptable toxicity.	Drug: Erlotinib; Erlotinib was supplied as tablets.; Other Names: Tarceva
Active Comparator: Chemotherapy; Participants received gemcitabine 1250 mg/m^2 intravenously (IV) on Days 1 and 8 and cisplatin 75 mg/m^2 IV on Day 1 of every 3 week cycle until disease progression, unacceptable toxicity, or a total of 4 cycles, whichever came first.	Drug: Chemotherapy; Cisplatin and gemcitabine were locally sourced with commercial products.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigator-assessed Duration of Progression-free Survival	The duration of progression-free survival was defined as the time from randomization to disease progression (PD) or death from any cause, whichever occurs first. PD was defined as: (1) At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this may include the baseline sum). The sum must also demonstrate an absolute increase of at least 5 mm. (2) An unequivocal progression of existing non-target lesions. When the patient has measurable disease, the overall tumor burden must have increased sufficiently to merit discontinuation of therapy. When the patient has only non-measurable disease, the increase in overall disease burden should be comparable in magnitude to the increase that would be required to declare PD for measurable disease. (3) The appearance of new malignant lesions.	Baseline to the data cut-off date of 20 Jul 2012 (1 year, 4 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Responders as Assessed by the Investigator	A responder was defined as a participant with either a complete response (CR) or a partial response (PR), as determined using the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. A CR was defined as: (1) The disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to < 10 mm. (2) The disappearance of all non-target lesions and normalization of tumor marker levels. All lymph nodes must be non-pathological in size (< 10 mm in the short axis). A PR was defined as: (1) At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. (2) The persistence of 1 or more non-target lesion(s) and/or maintenance of tumor marker levels above normal limits.	Baseline to the data cut-off date of 19 Nov 2012 (1 year, 8 months)
Percentage of Participants With Disease Control	A participant with disease control was defined as a participant with either a complete response (CR), a partial response (PR), or stable disease (SD), as determined using RECIST v1.1. A CR was defined as the disappearance of all target lesions (TL). A PR was defined as at least a 30% decrease in the sum of the longest diameter of TLs taking as reference the Baseline sum longest diameter (SLD). SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest SLD since treatment started. For non-TLs, SD was defined as the persistence of 1 or more lesions. PD was defined as at least a 20% increase in the SLD of TLs, taking as reference the smallest SLD recorded since treatment started or the unequivocal progression of existing non-TLs. A SLD for all TLs will be calculated and reported as the Baseline SLD.	Baseline to the data cut-off date of 19 Nov 2012 (1 year, 8 months)
Duration of Response	Duration of response was defined as the time from the first documented complete response (CR) or partial response (PR) to the first documented disease progression (PD) or death, whichever occurs first. A CR was defined as the disappearance of all target lesions (TL). A PR was defined as at least a 30% decrease in the sum of the longest diameter (SLD) of TLs taking as reference the Baseline SLD. PD was defined as at least a 20% increase in the SLD of TLs, taking as reference the smallest SLD recorded since treatment started or the unequivocal progression of existing non-TLs.	Baseline to the data cut-off date of 19 Nov 2012 (1 year, 8 months)
Overall Survival	Overall survival was defined as the time from the date of randomization to the date of death from any cause.	Baseline to the end of the study (3 years, 1 month)
Safety: Incidence of Adverse Events		36 months
Quality of Life: Functional Assessment of Chronic Illness Therapy - Lung (FACIT-L) Questionnaire		approximately 21 months

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Wen F, Zheng H, Zhang P, Hutton D, Li Q. OPTIMAL and ENSURE trials-based combined cost-effectiveness analysis of erlotinib versus chemotherapy for the first-line treatment of Asian patients with non-squamous non-small-cell lung cancer. BMJ Open. 2018 Apr 13;8(4):e020128. doi: 10.1136/bmjopen-2017-020128.
• Wu YL, Zhou C, Liam CK, Wu G, Liu X, Zhong Z, Lu S, Cheng Y, Han B, Chen L, Huang C, Qin S, Zhu Y, Pan H, Liang H, Li E, Jiang G, How SH, Fernando MCL, Zhang Y, Xia F, Zuo Y. First-line erlotinib versus gemcitabine/cisplatin in patients with advanced EGFR mutation-positive non-small-cell lung cancer: analyses from the phase III, randomized, open-label, ENSURE study. Ann Oncol. 2015 Sep;26(9):1883-1889. doi: 10.1093/annonc/mdv270. Epub 2015 Jun 23.

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: April 26, 2011
• First Submitted That Met QC Criteria: April 26, 2011
• First Posted (Estimate): April 27, 2011

Study Record Updates

• Last Update Posted (Estimate): February 24, 2015
• Last Update Submitted That Met QC Criteria: February 5, 2015
• Last Verified: February 1, 2015

More Information

Terms related to this study

• 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
• Other Study ID Numbers: YO25121