MTAP deletion marks poorer survival in pancreatic cancer cohort

A large retrospective study of US patients with pancreatic ductal adenocarcinoma (PDAC) has quantified how often the MET-adjacent gene MTAP is deleted in routine clinical practice and how that molecular feature tracks with treatment patterns and survival. Drawing on the Flatiron Health Foundation Medicine Clinico-Genomic Database, researchers followed 2,694 patients diagnosed between January 1, 2011 and June 30, 2024 whose tumors underwent next-generation sequencing, observing treatments and outcomes through December 31, 2024. The work, published open access in BMC Cancer, arrives as a new class of MTA-cooperative PRMT5 inhibitors enters clinical development, making real-world characterization of MTAP status increasingly consequential for treatment planning.

The central molecular finding was that 823 of the 2,694 patients, or 30.5 percent, carried MTAP-deleted tumors, confirming that the alteration is common in PDAC rather than a rare subtype. Co-deletion patterns were striking: CDKN2A, a neighboring gene on chromosome 9, was deleted in 100 percent of MTAP-deleted tumors but only 18 percent of MTAP-wildtype tumors, consistent with the shared genomic region affected. KRAS mutations were highly prevalent in both groups, at 94.5 percent among MTAP-deleted and 91.8 percent among MTAP-wildtype patients, with G12X variants accounting for 85 percent of KRAS mutations. Few patients in the cohort received targeted therapies, underscoring how limited the molecularly matched options remain for this disease.

Clinically, metastatic disease at diagnosis was slightly more frequent among MTAP-deleted patients, 61 percent versus 55 percent of MTAP-wildtype patients. Among metastatic patients, roughly 73 percent received at least one line of therapy, and regimen selection was nearly identical across MTAP strata: FOLFIRINOX was used first-line in 39 percent of each group, and gemcitabine plus nab-paclitaxel in 37 percent of MTAP-deleted and 38 percent of MTAP-wildtype patients. In the second-line setting, gemcitabine plus nab-paclitaxel was the most common regimen, given to 40 percent of MTAP-deleted and 44 percent of MTAP-wildtype patients. The similarity of treatment patterns suggests that MTAP status has not, to date, driven differential therapeutic decisions in routine US practice.

Survival analyses using Kaplan-Meier estimation in metastatic patients revealed a consistent survival disadvantage associated with MTAP deletion. Median overall survival from first-line therapy was 6.4 months (95 percent confidence interval 5.7 to 7.0) for MTAP-deleted patients compared with 7.3 months (95 percent CI 6.7 to 7.8) for MTAP-wildtype patients. Median time to next treatment, a proxy for duration of first-line benefit, was 3.8 months (95 percent CI 3.3 to 4.2) versus 4.4 months (95 percent CI 4.1 to 4.8). In stratified analyses, patients whose tumors were both MTAP-wildtype and KRAS-wildtype had the longest median overall survival at 10.3 months (95 percent CI 8.0 to 12.8), and the pattern of lower overall survival among MTAP-deleted patients held across patient subgroups examined.

The authors frame these results as evidence of high unmet need in MTAP-deleted PDAC, a population that currently receives the same cytotoxic regimens as everyone else yet fares modestly worse. The study’s limitations are those inherent to a retrospective, observational database cohort: survival differences are associations from selected real-world populations rather than causal effects, and the authors themselves note that the lower overall survival estimates in selected MTAP-deleted subgroups warrant further investigation. Still, as molecularly selected trials of PRMT5 and RAS-targeted agents advance, this cohort provides a practical baseline for how MTAP deletion distributes across PDAC and what outcomes current standard therapy delivers.

Subject of Research: Real-world clinical and molecular characterization of MTAP deletion in pancreatic ductal adenocarcinoma

Article Title: Clinical relevance of MTAP deletion in pancreatic ductal adenocarcinoma: a real-world US patient cohort study

Article References: Hildebrand, J. S., Capasso, A., Payne, R., Gerrick, K. Y., Hindoyan, A., Zhang, A., Clouser, M. C., Eggert, T., Huang, X., & Wainberg, Z. A. (2026). Clinical relevance of MTAP deletion in pancreatic ductal adenocarcinoma: a real-world US patient cohort study. BMC Cancer. https://doi.org/10.1186/s12885-026-17215-4

Image Credits: AI Generated

DOI: 10.1186/s12885-026-17215-4

Keywords: MTAP deletion, pancreatic ductal adenocarcinoma, PRMT5 inhibitors, KRAS mutation, overall survival, CDKN2A, real-world evidence, clinico-genomic database, FOLFIRINOX, gemcitabine nab-paclitaxel, precision oncology, Clinical