Treatment patterns and outcomes in patients diagnosed with metastatic pancreatic ductal adenocarcinoma (PDAC) and by methylthioadenosine phosphorylase (MTAP) status.

678 Background: PDAC is one of the lead causes of cancer-related mortality in the United States (US). MTAP is a key metabolic regulator, and MTAP deletion (del) has been associated with poor prognosis, poor response to chemotherapy and an immunosuppressed microenvironment in many cancers, including PDAC ( MTAP del occurs in approximately 20-25% of PDAC). This study describes real-world (RW) treatment patterns and clinical outcomes in PDAC patients with and without MTAP del tumors. Methods: Patients 18+ years old were included from the US-based de-identified Flatiron Health- Foundation Medicine Clinico-Genomic Database. Patients were diagnosed with metastatic PDAC between July 2010 and June 2024 (index date). MTAP del, KRAS , and BRCA mutations were reported at index date. Treatment patterns included line of therapy (LOT) and were assessed via descriptive statistics. RW overall survival (OS) was reported for the two primary treatment groups: Group 1 = gemcitabine and nab-paclitaxel combinations; Group 2 = FOLFIRINOX. RW OS was reported as median months (mOS) with 95% confidence intervals (CI) and estimated via Kaplan-Meier analysis. Results: The overall cohort included n=1,588 patients with median age at index of 68 years, 53% (n=837) male, 62% (n=988) White, 71% (n=1,134) treated in community practices, 51% (n=803) with smoking, history and 31% (n=497) harboring homozygous MTAP del at index. From the 497 MTAP del cohort, co-mutations occurred in KRAS G12C (n=7, 1%) , G12D (n=200, 39%) , G12R (n=72, 15%) , and G12V (n=141, 28%) and rare co-mutations in BRCA1 (n=8, 2%) and BRCA2 (n=10, 2%) were observed. Similar co-mutations proportions were observed for the 1,091 MTAP wild type PDAC patients at index. 1,242 out of 1,588 patients were treated with ≥1LOT with breakdown of outcomes by treatment groups and MTAP del status (Table). 903 out of 1,242 patients received Group 1 and 2 treatments. Median duration of treatment for Group 1 and 2 was 3.0 and 3.3 months, respectively. Conclusions: In this real-world analysis, PDAC prognosis remains poor, including for patients with MTAP del tumors. Novel therapies, including those targeting MTAP del , are highly needed to improve outcomes in PDAC. Select treatment patterns and outcomes. All treated** MTAP del MTAP wild type N, % mOS* N, % mOS* N, % mOS* 1LOT 1,242, 100% 9.1 (8.4, 9.9) 395, 100% 7.9, (6.7, 9.0) 847, 100% 9.8, (8.8, 10.5) Group 1 459, 37% 7.9 (7.2, 9.8) 146, 37% 7.0 (5.7, 9.3) 313, 37% 8.5 (7.3, 10.3) Group 2 444, 36% 11.2 (9.9, 12.4) 138, 35% 8.8 (7.2, 12.3) 306, 36% 11.8 (10.1, 13.1) *Median months, 95% CI. **N=339 received 1LOT that was not in Group 1 and 2. Within this group, the Top 5 treatments were: FOLFOX (N=62); Clinical Study Drug (N=60); Gemcitabine (N=49); Fluorouracil, Irinotecan Liposomal, Leucovorin (N=35); Capecitabine (N=34).