A Man Aged 82 Years With Metastatic Pancreatic Adenocarcinoma

A panelist discusses how a man aged 82 years with good performance status presented with unexplained weight loss and abdominal pain, leading to a diagnosis of metastatic pancreatic adenocarcinoma with KRAS G12D and TP53 mutations confirmed through imaging, biopsy, and next-generation sequencing (NGS) testing.

A panelist discusses how first-line treatment for metastatic pancreatic cancer depends on performance status. ECOG 0-1 patients receive preferred options like FOLFIRINOX, modified FOLFIRINOX, or the newly FDA-approved NALIRIFOX regimen (which includes liposomal irinotecan for enhanced drug delivery), whereas ECOG 2 patients typically receive gemcitabine plus nab-paclitaxel, and ECOG 3 patients receive palliative care.

A panelist discusses how treatment selection for metastatic pancreatic adenocarcinoma involves evaluating multiple factors including genetic and somatic mutations (particularly homologous recombination deficiency [HRD] alterations like BRCA1/2 and PALB2, which favor platinum-based regimens), patient age and performance status, liver function status, and drug metabolism genotype testing such as dihydropyrimidine dehydrogenase (DPD) deficiency screening to avoid severe 5-FU toxicity in rare cases of homozygous variants.

Overview of Clinical Trial Data A panelist discusses how first-line treatment recommendations are based on 3 pivotal phase 3 randomized trials: PRODIGE 4 (which established FOLFIRINOX superiority over gemcitabine with 11.1 vs 6.8 months overall survival despite higher toxicity), MPACT (showing gemcitabine plus nab-paclitaxel benefit over single-agent gemcitabine with 8.5 vs 6.7 months survival), and the recent NAPOLI-3 (demonstrating NALIRIFOX superiority over gemcitabine plus nab-paclitaxel with 11.1 vs 9.2 months overall survival in over 750 patients across 180 sites).

A panelist discusses how treating metastatic pancreatic cancer requires a multidisciplinary approach with early palliative care and dietitian involvement, emphasizing that for patients with good performance status, 3-drug regimens like NALIRIFOX or modified FOLFIRINOX can provide clinical responses and quality-of-life improvements even in high disease burden cases, whereas frail patients benefit from gemcitabine plus nab-paclitaxel administered every 2 weeks, and notes that age alone should not exclude patients from 3-drug regimens as the NAPOLI-3 trial included patients aged up to 85 years.

A panelist discusses how proactive adverse event management is crucial for patients with metastatic pancreatic cancer, including using every-2-week scheduling and primary granulocyte colony-stimulating factor (G-CSF) support to reduce myelosuppression, providing extensive patient counseling about diet, hydration, and early antidiarrheal use for liposomal irinotecan-related diarrhea, and closely monitoring for cumulative neuropathy with consideration of oxaliplatin discontinuation by 3 to 4 months if responding to prevent limitations on future therapy options.

A panelist discusses how this is an exciting time for pancreatic cancer treatment with the development of RAS inhibitors targeting KRAS mutations (present in approximately 90% of patients with metastatic pancreatic cancer, including G12D, G12V, and G12C variants), which have shown impressive response rates in later-line settings and are being evaluated in frontline trials, before concluding the Targeted Oncology discussion on the metastatic pancreatic adenocarcinoma treatment landscape.