Clinical Experience in Treating Metastatic Disease

Clinical Experience and Treatment Management

Clinical management of metastatic pancreatic adenocarcinoma requires a comprehensive team-based approach, given the aggressive nature of the disease, with 5-year survival rates of only 10% to 12%. Essential elements include early goals-of-care discussions acknowledging the serious prognosis, routine palliative care referrals at initial diagnosis, and dietitian consultations to address nutritional challenges that become particularly important during active chemotherapy. For patients with good performance status and acceptable liver function, 3-drug regimens including NALIRIFOX and modified FOLFIRINOX have demonstrated meaningful clinical responses, even in patients with high disease burden and visceral metastases. The primary benefit observed with these intensive regimens is improved patient symptoms and quality of life. However, proactive toxicity management remains crucial to ensure treatment does not become worse than the disease itself.

Treatment selection strategies must consider patient tolerance and functional capacity, with flexible dosing approaches improving tolerability. For patients unable to tolerate 3-drug regimens, gemcitabine plus nab-paclitaxel represents a reasonable alternative, particularly when administered every 2 weeks rather than the standard 3-weeks-on, 1-week-off schedule, resulting in reduced myelosuppression and neuropathy. Visceral disease, including liver metastases, carries a worse prognosis across cancer types, but NAPOLI-3 subset analyses demonstrated consistent survival benefits with NALIRIFOX across different subgroups, including those with hepatic involvement. The trial showed numerically higher overall response rates with NALIRIFOX (42% vs 36%), although this difference did not reach statistical significance.

Age considerations have evolved significantly with the accumulation of clinical evidence. Although the original PRODIGE4 trial excluded patients older than 75 years, NAPOLI-3 included patients up to 85 years, with approximately 7% being 75 or older, providing confidence for age-inclusive treatment decisions. Performance status rather than chronological age should guide treatment selection, making 3-drug regimens like NALIRIFOX appropriate for patients with adequate functional capacity regardless of age. Many patients present with high disease burden and may never receive second-line therapy, emphasizing that the first treatment opportunity represents the best chance for meaningful clinical benefit.