Characteristics of Non-Small Cell Lung Cancer patients with MTAP loss detected, Treatment Landscape and Associated Outcomes

Objectif(s) de la recherche et intérêt pour la santé publique

Finalité de l'étude

Objectifs poursuivis

Domaines médicaux investigués

Bénéfices attendus

Public Interest:

Advanced and metastatic non-small cell lung cancer (NSCLC) remains associated with poor prognosis despite advances in targeted therapies and immunotherapy. MTAP deletion represents an emerging molecular alteration for which there are currently no approved targeted treatments. Although MTAP loss may identify a clinically relevant subgroup of patients with distinct outcomes and therapeutic needs, MTAP status is not routinely assessed in clinical practice, and real-world evidence describing these patients remains limited.
As a result, the clinical characteristics, treatment patterns, and outcomes of patients with MTAP-deleted NSCLC are not yet well understood. This study will help address this knowledge gap by generating real-world evidence on patients with advanced or metastatic NSCLC according to MTAP status, contributing to a better understanding of potential clinical differences and unmet medical needs, and supporting the development of future MTAP-targeted treatment strategies

Objectives:
Primary Objectives:
1. To describe the demographic and clinical characteristics of methylthioadenosine phosphorylase (MTAP) loss detected (LD) and no MTAP loss detected (MTAP NLD) patients.
2. To describe treatment patterns and treatment sequencing for MTAP LD and MTAP NLD patients, up to and inclusive of third line (3L) systemic therapy.

Secondary Objectives:
1. To describe the real-world progression-free survival (rwPFS) of MTAP LD and MTAP NLD patients, measured from initiation of first-line (1L) systemic therapy.
2. To describe the overall survival (OS) among MTAP LD and MTAP NLD patients, measured from initiation of 1L systemic therapy.
3. To describe the time to next treatment or death (TTNT/D) of MTAP LD and MTAP NLD patients, measured from initiation of 1L systemic therapy.

Exploratory Objectives:
1. To describe the rwPFS of MTAP LD and MTAP NLD patients, measured from initiation of second line (2L) systemic therapy, among patients who initiate 2L systemic therapy.
2. To describe the OS of MTAP LD and MTAP NLD patients, measured from initiation of 2L systemic therapy, among patients who initiate 2L systemic therapy.
3. To describe the TTNT/D of MTAP LD and MTAP NLD patients, measured from initiation of 2L systemic therapy, among patients who initiate 2L systemic therapy.
4. To compare rwPFS of MTAP LD and MTAP NLD patients, measured from initiation of 1L systemic therapy.
5. To compare OS of MTAP LD and MTAP NLD patients, measured from initiation of 1L systemic therapy.
6. To compare TTNT/D of MTAP LD and MTAP NLD patients, measured from initiation of 1L systemic therapy.
7. To estimate the proportion of MTAP LD among consecutively tested patients at participating sites with evaluable immunohistochemistry (IHC) results.

Methodology:
This is a multi-country, retrospective, observational cohort study of adult (≥18 years) patients
with advanced or metastatic non-small cell lung cancer (NSCLC), who have a recorded initiation of 1L systemic therapy and an available archived tumor tissue sample.
The study will utilize data collected from participating sites in France, Germany and the United Kingdom (UK). To ensure harmonization and consistency in analysis and reporting, an electronic case report form (eCRF) will be implemented across all data sources.
The overall study period represents the calendar time during which exposures and outcomes are assessed and extends from 1 January 2023 to 31 December 2026. Data will be extracted after the end of the study period. The patient identification period is the timeframe during which eligible patients are identified and may enter the study population, spanning from 1 January 2023 to 31 December 2025. Patients will enter the study population on the index date, defined as the date of initiation of 1L systemic therapy, as recorded by participating sites, within the patient identification period.
The follow-up period is defined as the period extending from the index date (inclusive) until the earliest of the following (unless otherwise specified for a given endpoint): initiation of a clinical trial, the end of the study period (31 December 2026), loss to follow-up, or death.
The study will utilize archived tissue samples, as well as secondary data pooled from participating sites' electronic medical records (EMRs).
Data will be entered into a standardized eCRF to ensure harmonized data collection across sites. Information collected will include demographic characteristics, clinical characteristics, treatment patterns, clinical outcomes, and tissue sample characteristics.
The main analytic cohort is planned to include 150 patients (comprising 75 MTAP LD and 75 MTAP NLD patients). MTAP status will be assessed in all eligible patients using IHC, performed at each site according to site-specific methods. Consecutive testing will continue until the overall target of 75 MTAP LD patients has been reached across participating sites.
From the pool of consecutively tested MTAP NLD patients, a random sample of 75 patients will be selected, with sampling stratified by site and calendar year of 1L initiation.

All analyses will be performed by MTAP deletion status. Demographic characteristics, clinical features, treatment patterns, and sequencing, will be summarized using descriptive statistics. Time-to-event outcomes, including real-world progression-free survival (rwPFS), overall survival (OS), and time to next treatment or death (TTNT/D), will be evaluated using Kaplan-Meier methods. separated by MTAP status and line of therapy. Exploratory comparative analyses will use propensity score methods and overlap-weighted Cox regression models.

Study Population:

The source population of this study includes adult patients (aged ≥18 years at the time of NSCLC diagnosis) with advanced or metastatic NSCLC treated at participating sites. Advanced or metastatic disease is defined as either disease with initial diagnosis at stage III-IV or disease progressing from an initial early-stage (stage I-II) to an advanced or metastatic stage, as documented by participating sites. To be eligible for inclusion in the study population, adult patients in the source population must have advanced or metastatic NSCLC, subsequently initiate 1L systemic therapy within the patient identification period and have an available archived tumor tissue sample obtained prior to or at index date (initiation of 1L systemic therapy), that is suitable for MTAP status assessment via tissue re-testing.