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Metastatic Pancreatic Cancer Treatment
Navigating Treatment Algorithms in Metastatic Pancreatic Cancer

Released: October 01, 2025

Zev A. Wainberg
Zev A. Wainberg, MD
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Key Takeaways
  • Tailoring first-line chemotherapy to patient performance status and preferences is essential.
  • Early dose adjustments for toxicity management improve quality of life.
  • Multidisciplinary care is critical to sustaining therapy and addressing adverse events.

Introduction
Metastatic pancreatic ductal adenocarcinoma (mPDAC) remains one of the more difficult malignancies encountered in oncology. Despite incremental progress over the last decade, its incidence continues to rise, and its prognosis remains unforgiving. Most patients still present with metastatic disease, and the urgency to initiate therapy often coincides with systemic compromise from tumor burden. In this commentary, Zev A. Wainberg, MD, shares a practical perspective on how to approach mPDAC treatment in 2025—focusing on first-line and subsequent lines of therapy, how to navigate chemotherapy-related toxicities, and what multidisciplinary care looks like in practice.

Diagnosed Too Late, Treated Under Pressure
Unlike cancers where patients can be asymptomatic at diagnosis, most patients with pancreatic cancer present with advanced symptoms such as pain, weight loss, jaundice, or fatigue. By the time they are seen, they have often already suffered a systemic insult. Sometimes such an insult is measurable through markers like C-reactive protein or albumin, and other times it is more intangible but can be felt in the room. Patient fragility shapes every clinical decision. These patients have real burdens, so healthcare professionals (HCPs) must act quickly but thoughtfully.

First-line Chemotherapy: Personalizing What Is Available
Chemotherapy is still the foundation of treatment in metastatic pancreatic cancer. Regardless of the regimen used (eg, FOLFIRINOX, gemcitabine plus nab-paclitaxel, or NALIRIFOX), treatment choices are guided by performance status, symptoms, comorbidities, and patient preferences.

In practice, I find that even when patients are hesitant to initiate treatment, they become open to it when the goal is reframed: the goal is not to simply prolong their lives by months; rather, the goal is to feel better during those months. Most studies and personal experiences show that patients receiving chemotherapy tend to do better symptomatically than those who are not.

I believe it is important to be candid with these patients. Yes, treatment is arduous, but if symptoms can be relieved (ie, patients are able to eat and engage in activities of daily living), even for a few months, the benefit is meaningful. I spend time talking patients through not only treatment options but also the expected side effects and how to manage them. These conversations are as important as the regimen itself.

Mitigating Toxicities Through Early Adjustment
Managing side effects is where oncology becomes truly multidisciplinary. Nurses, NPs, pharmacists—everyone—must stay ahead of toxicities. Usual toxicities such as peripheral neuropathy, diarrhea, and cytopenias are frequently seen, for which chemotherapy can and should be adjusted early and often. There is no prize for pushing full-dose chemotherapy if the patient is unable to tolerate it.

Real decisions such as dose reductions, delays for family events, or simply holding a drug like oxaliplatin once neuropathy starts make care safer and more sustainable. Clinical trials might list fixed doses, but even in trials, dose modifications are the norm. The key to success is flexibility guided by vigilance.

Second-line Therapy: Individualization Matters Even More
In the second-line setting, treatment options are limited and the margin for benefit shrinks. Nevertheless, we should not abandon ship. Instead, adjust the treatment plan based on what patients tolerated before, what toxicities emerged, and what the disease is doing.

If neuropathy is dominant, I avoid oxaliplatin. If diarrhea was an issue, I might avoid irinotecan. At this point, the goal is to make the best of limited tools while preserving dignity and minimizing harm. There is no standard sequence, no ‘one-size-fits-all’ approach. Every choice is contextual for that individual person in front of you.

The Road Ahead
For the first time in a long time, I feel a sense of cautious optimism. Patients are asking me about KRAS inhibitors, immunotherapy combinations, and enrollment in clinical trials. Novel agents with real biologic rationale are emerging, and perhaps more importantly, we are starting to discuss how to bring these options into earlier lines of care.

The field is accelerating, and our ability to guide patients based on both data and compassion is more important than ever.

Summary
Treating metastatic pancreatic cancer requires humility, adaptability, and teamwork. Chemotherapy remains the cornerstone of treatment, but how it is used, who it is used on, how doses are modified, and how HCPs support patients define success. As new therapies emerge, HCPs must stay grounded in the fundamentals of clinical judgment and human connection. 

Your Thoughts
How do you approach first- and second-line chemotherapy for your patients with advanced pancreatic cancer? What strategies have helped you balance efficacy and toxicity? We’d love to hear your experience.

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