LOREA _ ANALYSIS OF THE EFFECTIVENESS AND SAFETY OF LORLATINIB IN UNTREATED ALK-POSITIVE NSCLC PATIENTS IN A FRENCH REAL-WORLD CONTEXT

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Effectiveness study (incl. comparative)

  Safety study (incl. comparative)

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Medicinal product name, other:
  Lorlatinib
• Study drug International non-proprietary name (INN) or common name:
  LORLATINIB
• Anatomical Therapeutic Chemical (ATC) code:
  (L01ED05) lorlatinib

  lorlatinib

Population studied

• Short description of the study population:
  This study can fulfill its objectives only if appropriate participants are enrolled. The eligibility criteria are designed to select participants for whom participation in the study is considered appropriate. ; Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as protocol waivers or exemptions, is not permitted.; ; The target population includes ALK-positive locally advanced or metastatic NSCLC patients for whom Lorlatinib was initiated in first line during the inclusion period, expected to be 18 months to reach sample size. ; For each patient, follow-up will extend from the date of inclusion to the end of data collection or date of withdrawn consent or the date of death whichever comes first. The end of data collection will correspond to the end of study visit: 25 months after the inclusion of the patient, or one month after the date of lorlatinib withdrawn due to toxicity or disease progression.;
• Age groups:
  • Adult and elderly population (≥18 years)
• Estimated number of subjects:
  90

Study design details

• Study design:
  The LOREA study was designed as a French multicenter, observational prospective cohort, to collect data concerning ALK-positive locally advanced or metastatic NSCLC patients treated with lorlatinib in first line, as per standard of care (see Figure 1 - Study design).
• Main study objective:
  • Primary objective; To evaluate Progression Free Survival (PFS) rate, assessed by investigator in a real-world setting, of ALK- positive locally advanced or metastatic NSCLC patients treated with lorlatinib in first-line.;
• Setting:
  Approximately 30 sites are expected to participate in the study.; Eligible patients, with ALK-positive locally advanced or metastatic NSCLC for whom lorlatinib treatment is planned, will be proposed the study during a routine visit. Patients will be included in the study after providing informed consent.
• Data analysis plan:
  Detailed methodology for summary and statistical analyses of data collected in this study will be documented in a statistical analysis plan (SAP), which will be dated, filed and maintained by the sponsor. The SAP may modify the plans outlined in the protocol; any major modifications of primary endpoint definitions or their analyses would be reflected in a protocol amendment.; The statistical analysis will be mainly descriptive. Summary statistics will be presented for continuous variables, by way of n, n missing (if any), mean, standard deviation (SD), median, first and third quartiles (Q1 and Q3), minimum and maximum. Qualitative/categorical variables will be presented in terms of number and percentage of each modality and number of missing and non-missing observations. Unless otherwise stated, the percentages will only be calculated for the modalities provided, excluding missing data.; Effectiveness will be assessed on the I(FAS) defined as all eligible and treated patients. Safety will be assessed on the Safety Analysis Set defined as all treated patients.; PFS and OS will be described using the Kaplan-Meier method. Survival function estimates will be provided at 12, 24 and 36 months with 95% CIs that will be derived using the log-log transformation according to Kalbfleisch and Prentice, with back transformation to a CI on the untransformed scale. The median event-free time will be estimated with a 95% CI calculated according to the Brookmeyer and Crowley method.; Subgroup analyses (absence/presence of CNS metastases at baseline) will be conducted for all effectiveness endpoints.;