Carcinoma, Non-Small-Cell Lung
Conditions
Keywords
EGFR, EGFR mutation, EGFRm, EGFR-TKI, Health care resource utilization, Health-Related Quality of Life, Locally advanced or metastatic lung cancer, NSCLC, Non-Small Cell Lung Cancer, Observational study, Osimertinib, Personalized medicine, PRO, Patient Reported Outcome, Resistance, T790M, Carcinoma, Non-Small-Cell Lung, Carcinoma, Bronchogenic, Bronchial Neoplasms, Lung Neoplasms, Respiratory Tract Neoplasms, Thoracic neoplasms, Neoplasms by site, Lung diseases, Respiratory Tract diseases, Cancer Chemotherapy, Combination Chemotherapy, Immunotherapy, Radiation
Brief summary
This is an observational cohort study of patients with locally advanced or metastatic NSCLC (non-small cell lung cancer). Patients will be recruited from participating sites in Europe, Asia, and Canada. The study will include 2 patient cohorts.
Detailed description
Study Design This will be an observational cohort study of patients with locally advanced or metastatic NSCLC (non-small cell lung cancer). Patients will be recruited from participating sites in Europe, Asia, and Canada. Patients meeting the study inclusion/exclusion criteria will be selected during a 24-month enrolment period per country and will be followed from enrolment in the study until death, loss to follow-up, withdrawal of consent or study end date (whichever occurs earlier). Data Sources Data will be collected following enrolment in the study and entered in the electronic case report form (eCRF). All data will be collected using patient medical records. The investigator will be responsible for ensuring that all the required data is collected and entered into the eCRF. The site will collect the patient questionnaires and the data will be uploaded according to the data entry procedures. Study Population * Adult male or female patients (according to age of majority/adulthood as defined by local regulations) who have given written informed consent as per local regulations. * The primary cohort will include patients with EGFR (epidermal growth factor receptor) mutation-positive locally advanced or metastatic NSCLC who have progressed while on or after receiving front-line EGFR-TKI (tyrosine kinase inhibitors) therapy (e.g., gefitinib, erlotinib, afatinib, or icotinib). * Additionally, a secondary cohort of patients will include patients newly diagnosed with locally advanced or metastatic NSCLC who are treatment naive or patients who were diagnosed at an earlier stage but have progressed to metastatic NSCLC during the selection period. Exposures There are no specific drug exposures or interventions being evaluated, as cohort eligibility (for both cohorts) is not exposure-based, but rather disease-based. All molecular testing and treatments will be at the discretion of the treating physician. Study Measures and Outcomes * Patient demographic and clinical characteristics * Molecular testing patterns and outcomes * Treatment patterns * Physician-reported clinical outcomes * Cancer-related health care utilization * Treatment- and biopsy-related complications * CNS metastases (brain metastases and leptomeningeal metastases) and treatments associated with CNS (central nervous system) metastases * HRQoL (Health Related Quality of Life) and symptoms Precision and Sample Size Estimations For the primary cohort the minimum sample size recommended for conducting a country-level analysis is 200 patients per country. This is based on the precision estimation calculation for the categorical study measure (% of patients tested) and will allow a maximum of * 8.3% precision (i.e., assuming 50% undergoing molecular testing) around the point estimate for the categorical measure. For the secondary cohort the minimum sample size recommended for conducting a country-level analysis is 300 patients which was determined using precision estimates calculated for a categorical (% of patients tested) and a time-to-event (overall survival) measure. The overall study will include approximately 2800-3300 patients across all participating countries across both primary (1200-1300 patients) and secondary (1600-2000 patients) cohorts. Statistical Analysis No formal hypothesis testing is specified. Study measures including patient demographics and clinical characteristics, molecular testing patterns, treatment sequence patterns, physician-reported outcomes (overall survival) and patient-reported outcomes (HRQoL) will be reported by primary and secondary cohorts, unless indicated otherwise. Continuous study measures (e.g., age, duration of therapy) will be reported descriptively with mean, standard deviation, median, minimum and maximum. Frequencies and percentages will be used to document categorical measures of interest (e.g., number and proportion of patients with a post progression molecular test, number and proportion of patients with a T790M mutation) and will include 95% CIs for key outcome variables. Kaplan-Meier curves and median survival will be estimated, overall and on an exploratory basis by clinical and treatment characteristics of interest (provided there are sufficient events available; e.g., chemotherapy vs. targeted therapy) as pre-specified in the statistical analysis plan.
Interventions
OTHERPatient Reported Outcomes
HRQoL will be assessed using questionnaire EORTC QLQ-C30 and the questionnaire EORTC QLQ-LC 13. These two questionnaires are validated instruments, translated in various languages and are not used as an intervention but rather to track patient quality of life and symptom reduction in real-life settings. Data for these patient reported outcomes will be collected prospectively from the time of enrolment until the end of follow-up. The two questionnaires will be self-administered by the patients in both cohorts at the enrolment visit and subsequently every 3 months (±1 month) at routine standard of care scheduled visits. The questionnaires are expected to take about 15 minutes to complete
Sponsors
AstraZeneca
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Provision of written informed consent - patient consent should be within 6 weeks of index date. * Adult male or female subjects (according to age of majority/adulthood as defined by local regulations)
Exclusion criteria
-Enrolment in studies that prohibit any participation in this non interventional study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Parameters in the target population associate with molecular testing patters | Patients will be followed from enrolment in the study until death, loss to follow-up, withdrawal of consent or study end date. The minimum follow-up will be 12 months and the maximum allowed follow-up will be 36 months | * Molecular testing rate defined as the number of patients identified as having received molecular testing divided by the number of patients in the cohorts * Changes in testing rates over time (details will be included in the SAP) * Molecular testing details including, but not limited to sample type, method of biopsy, testing turnaround time, test type, reason for testing, testing laboratory type, reason for not performing a test * Molecular testing results including mutation status and type, test outcome, histologic/phenotypic transformation |
| Parameters in the target population associate with treatment patterns and associated clinical outcomes | Patients will be followed from enrolment in the study until death, loss to follow-up, withdrawal of consent or study end date. The minimum follow-up will be 12 months and the maximum allowed follow-up will be 36 months | * Overall survival measured from: * the date of initial diagnosis to date of death from any cause to the index date to date of death from any cause (for primary cohort only) * the date of first-line treatment until death * the date of second-line treatment until death * Overall disease progression: o from date of treatment initiation until physician-reported progression, initiation of a new cancer-directed line of therapy (proxy for progression), or death * For each line of chemotherapy/targeted therapy received: * Therapy regimen * Therapy duration measured as time from therapy start date to time of therapy end date * Number of cycles received * Reason for cessation of therapy * Time to initiation of new therapy defined as the time from start date of current therapy to start date of subsequent therapy * For each surgery or radiotherapy received: * Type * Site * Date * Any palliative/supportive care received |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Estimation of parameters in the target population associate with cancer-related health care utilization patters including inpatient, emergency room, outpatient visits, lenght of inpatient stay | Patients will be followed from enrolment in the study until death, loss to follow-up, withdrawal of consent or study end date. The minimum follow-up will be 12 months and the maximum allowed follow-up will be 36 months | * For each health care setting: * Number and % of patients with visits * Total number of visits * Total length of inpatient hospital and ICU stay |
| Estimation of parameters in the target population associated with treatment- and biopsy-related complications | Patients will be followed from enrolment in the study until death, loss to follow-up, withdrawal of consent or study end date. The minimum follow-up will be 12 months and the maximum allowed follow-up will be 36 months | * For each treatment complication: o Rate of occurrence defined as the number of patients reporting at least one treatment-related complications divided by the number of evaluable patients2 Treatment-related complications can include, but are not limited to nausea and vomiting, diarrhoea, constipation, skin rash, infections, mouth sores, neutropenia, hyponatremia * For each biopsy-related complication: * Rate of occurrence defined as the number of patients reporting at least one occurrence of the complication divided by the number of patients receiving a biopsy Biopsy-related complications can include but are not limited to collapsed lung, severe bleeding, bronchial spasms, irregular heart rhythms, death, severe chest pain, light-headedness, trouble breathing, excessive bleeding through the bandage, haemoptysis, fever, infection |
| Estimation of the rate of CNS metastases in the target population including brain metastases and leptomeningeal metastases and treatments associated with CNS metastases | Patients will be followed from enrolment in the study until death, loss to follow-up, withdrawal of consent or study end date. The minimum follow-up will be 12 months and the maximum allowed follow-up will be 36 months | Overall CNS metastases rate, defined as the number of patients developing CNS metastases divided by the number of evaluable patients * Brain metastases rate, defined as the number of patients developing brain metastases divided by the number of evaluable patients * Leptomeningeal metastases rate, defined as the number of patients developing leptomeningeal metastases divided by the number of evaluable patients * Treatments for CNS metastases, including type of treatment and dates of treatment |
| Assessment of patient (HRQoL) using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 items (EORTC QLQ-C30) and EORTC QLQ - Lung Cancer 13 items (EORTC QLQ-LC13)3 | Patients will be followed from enrolment in the study until death, loss to follow-up, withdrawal of consent or study end date. The minimum follow-up will be 12 months and the maximum allowed follow-up will be 36 months | • Change in score from baseline for each Quality of Life (QoL) domain and for overall QoL, measured at each subsequent site visit |
Countries
Canada, China, France, Spain, Taiwan, United Kingdom
Outcome results
None listed