Metastatic pancreatic cancer: Molecular characterization, therapeutic implications, and survival outcomes from community oncology practice in western India.

Abstract

e16400 Background: Pancreatic cancer is a highly aggressive malignancy associated with poor survival outcomes. Next-generation sequencing (NGS) enables the identification of molecular alterations that may guide personalized therapeutic strategies and improve clinical management. Methods: This retrospective study included patients diagnosed with metastatic pancreatic cancer between March 2018 and September 2024. Survival analysis was performed using the Kaplan-Meier method. Results: A cohort of 111 patients with metastatic pancreatic adenocarcinoma was analyzed, with a median age of 63 years (IQR 55–70) and a F:M of 1:1.13. The predominant histologic subtype was adenocarcinoma n = 101(91.0%), followed by neuroendocrine tumors n = 2 (1.8%), while histology was unknown in n = 8 (7.2%). Mutational analysis using NGS identified detectable mutations in n = 86 (77.5%), with KRAS n = 45 (40.5%), and TP53 n = 41 (36.9%) being the most frequent alterations. Additional alterations included CDKN2A (n = 7, 6.3%), HER2 amplification (n = 4, 3.6%), SMADA (n = 4, 3.6%), BRCA2 (n = 2, 1.8%), BRCA1 (n = 1, 0.9%), BRAF (n = 1, 0.9%), and RET (n = 1, 0.9%) and variants of uncertain significance (VUS) (n = 7, 6.3%). PARP inhibitors were administered to 5/7 (including 2 VUS) patients and trastuzumab was given to all HER2-amplified patients. MSI-high was observed in 3 patients, TMB was high (> 10 muts/Mb) in 6 patients, and immunotherapy was administered to 3/9 patients. Tumor location analysis revealed a significant association between KRAS mutations and pancreatic tail tumors. (p = 0.037) Among KRAS mutations, G12D (n = 10/19) and G12V (n = 5/19) were the most frequent variants in head tumors, while G12D (n = 5/15), G12V (n = 5/15), and G12R (n = 1/15) were predominant in tail tumors. The median overall survival (mOS) for the entire cohort was 15.4 months (95% CI: 11.7–19.1), with a median follow-up duration of 21.6 months (95% CI: 14.1–29.1). The 2-year survival rate was 29.2% (95% CI: 0.19–0.46), and the median progression-free survival (PFS) was 8.7 months (95% CI: 6.7–11.3). The mOS was 18.7 months for KRAS -mutant/ TP53 -wild-type, 14.5 months for KRAS -wild-type/ TP53 -mutant, 14.6 months for KRAS -mutant/ TP53 -mutant, and 18.3 months for KRAS -wild-type/ TP53 -wild-type tumors ( p = 0.477). Conclusions: This study highlights the mutational profiling from western India and the need for affordable and accessible molecular testing to guide personalized treatment strategies. Given the aggressive nature of the disease and poor survival outcomes, personalised therapies are crucial for improving clinical outcomes.