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

Hoffmann-La Roche217 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

217

Conditions

Non-Small Cell Lung Cancer

Interventions

Erlotinib

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (28)

Unnamed facility

Beijing, China

Unnamed facility

Beijing, China

Unnamed facility

Changchun, China

Unnamed facility

Chongqing, China

Unnamed facility

Chongqing, China

Unnamed facility

Fuzhou, China

Unnamed facility

Guangzhou, China

Unnamed facility

Hangzhou, China

Unnamed facility

Nanjing, China

Unnamed facility

Shanghai, China

...and 18 more locations

Outcomes

Primary Outcomes

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.

Time frame: Baseline to the data cut-off date of 20 Jul 2012 (1 year, 4 months)

Secondary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Baseline to the end of the study (3 years, 1 month)

Safety: Incidence of Adverse Events

Time frame: 36 months

Quality of Life: Functional Assessment of Chronic Illness Therapy - Lung (FACIT-L) Questionnaire

Time frame: approximately 21 months