Characteristics of patients with Pancreatic Ductal Adenocarcinoma (PDAC) 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 Health Interest

Patients with PDAC with MTAP loss detected (MTAP LD) have limited treatment options beyond currently available systemic therapies. There are no approved targeted treatments for this subgroup, and outcomes remain poor once standard treatments fail. Real-world analyses show that MTAP LD patients have a significantly shorter time to standard therapy failure compared to those with MTAP WT tumours (11), highlighting a substantial unmet need. To address this gap, multiple early phase clinical trials across a range of cancer types are evaluating biomarker driven approaches targeting MTAP deletion, most notably MTA cooperative PRMT5 inhibitors (18–20). In PDAC specifically, ongoing clinical development includes the global, randomized Phase II/III MountainTAP-30 study, which is evaluating the selective, MTA-cooperative PRMT5 inhibitor Navlimetostat in combination with nab paclitaxel and gemcitabine as 1L therapy for MTAP LD patients with PDAC

Objectives

Primary Objectives
1. To describe the demographic and clinical characteristics of MTAP LD and MTAP NLD patients.
2. To describe treatment patterns and treatment sequencing for MTAP LD and MTAP NLD patients, up to and inclusive of 3L systemic therapy.
Secondary Objectives
1. To describe the rwPFS of MTAP LD and MTAP NLD patients, measured from initiation of 1L systemic therapy.
2. To describe the OS among MTAP LD and MTAP NLD patients, measured from initiation of 1L systemic therapy.
3. To describe the 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 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 IHC results.
8. To describe the distribution and overlap of MTAP loss detection by IHC and NGS, and to evaluate concordance between the two methods.

Elements of Method

This is a multi-country, retrospective, observational cohort study of adult patients with advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) diagnosed from July 2021 onwards, with an available banked tissue sample and initiation of first-line systemic therapy. Data will be collected from participating sites in France, Germany, and the United Kingdom using a study-specific electronic case report form (eCRF). Patients will be classified according to MTAP status determined by immunohistochemistry (IHC), with an additional concordance substudy comparing IHC and next-generation sequencing (NGS) results.
The study population consists of adult patients (≥18 years) with advanced or metastatic PDAC treated at participating sites who initiated first-line systemic therapy between 1 July 2021 and 31 December 2025 and have an available archived tissue sample suitable for MTAP assessment. The study aims to include approximately 250 patients (125 MTAP LD and 125 MTAP NLD).
The study will utilize routinely collected real-world data extracted from participating sites' electronic medical records (EMRs), together with information obtained from archived tissue samples. 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.
Analyses will primarily be descriptive and stratified by MTAP status. Demographic characteristics, clinical features, treatment patterns, and outcomes 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. 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 PDAC diagnosis) with advanced or metastatic PDAC treated at participating sites. Advanced or metastatic disease may be present at initial diagnosis or may arise from progression of earlier-stage PDAC; eligibility is determined by the presence of advanced or metastatic disease at the time of initiation of 1L systemic therapy for advanced/metastatic disease (index date).
To be eligible for inclusion in the study population, patients in the source population must have initiated 1L systemic therapy within the patient identification period and have an available banked tissue sample, obtained prior to or at index date, which is suitable for MTAP assessment via tissue re-testing. MTAP classification is therefore based on archived tissue obtained prior to or at the time of initiation of 1L systemic therapy.