Two large real-world studies of patients with metastatic pancreatic cancer — one from Netherlands and one from the US — paint strikingly different pictures of systemic therapy use.

A nationwide Dutch study reported that nearly three quarters of patients with metastatic pancreatic cancer did not receive systemic therapy, whereas a contemporary US cohort study found that only one third did not receive treatment.

The Dutch finding was “actually surprising” compared with US practice, noted Joel Saltzman, MD, medical oncologist at the Cleveland Clinic Taussig Cancer Center in Cleveland, who reviewed the studies for Medscape.

However, the differing treatment rates should not be viewed as a straightforward comparison, Saltzman cautioned, because they likely reflect who was captured in the datasets and differences in patient preferences and healthcare delivery.

Dutch Registry Study

The Dutch study, led by Thijmen H.T. Broekman, MSc, of Amsterdam University Medical Center, Amsterdam, Netherlands, included 13,756 adults with synchronous metastatic pancreatic cancer recorded in the nationwide Netherlands Cancer Registry from 2015 to 2023. Patients were asked whether they received systemic therapy.

Overall, 72% did not receive systemic therapy. The median overall survival was 213 days among patients who received treatment vs 42 days among those who did not.

Patient or family preference was the most frequently documented reason for not receiving treatment (39%), followed by comorbidities or impaired performance status (31%) and rapid progression or high tumor burden (25%).

Patients aged 80 years or older had more than 30-fold greater odds of not receiving systemic therapy than those younger than 59 years. For some older, frailer patients with limited life expectancy, forgoing chemotherapy may reflect an informed choice after weighing its potential survival benefit against toxicity and treatment burden, the Dutch team said.

Poor performance status, comorbidity, greater systemic inflammation, and lower socioeconomic position were also associated with not receiving treatment.

“The substantial proportion of patients who do not receive treatment in Netherlands may reflect informed decisions by patients and their families when weighing the modest median survival benefit of approximately 6 months against the symptom burden and potential treatment-related toxicity,” the authors explained.

However, “therapeutic nihilism” could not be ruled out, the researchers said, particularly because 68% of patients who did not receive treatment based on patient or family preference had a WHO performance status of 0-1.

Additionally, “it was unknown,” the authors said, “whether pros and cons of systemic therapy were discussed with a medical oncologist.”

A Different Picture in the US

The US study, led by Rupali Fuldeore, BAMS, MS, with Astellas Pharma Inc, Northbrook, Illinois, found almost the reverse pattern among patients with metastatic pancreatic cancer treated in oncology practices.

Among 9439 patients in the Flatiron Health electronic health record (EHR) database diagnosed from 2019 to August 2024, 33.5% had not received systemic anticancer therapy within 180 days of metastatic diagnosis, meaning about two thirds received treatment.

Among treated patients, the most common first-line regimens were gemcitabine plus nab-paclitaxel (41.5%) and folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX; 36.3%), and treatment began a mean of 26.9 days after diagnosis. The median overall survival was 3.7 months without systemic therapy, 7.6 months with gemcitabine plus nab-paclitaxel, and 10.7 months with FOLFIRINOX.

Poor functional status, early mortality, preference for hospice- or supportive-focused care, and incomplete treatment captured in the EHR may help explain decisions not initiate systemic therapy, the authors said. However, for some patients, not receiving systemic therapy “may reflect unmet need or gaps in access to care,” the authors noted.

Not an Apples-to-Apples Comparison

Saltzman told Medscape Medical News that one important explanation for the different findings may be the different populations captured by the two databases.

The Dutch study used a nationwide population-based cancer registry, which could include patients diagnosed in the hospital who opted against treatment or never saw a medical oncologist. The US study, by contrast, used an EHR database, which largely reflects patients seen in community and academic oncology practices, he explained.

Saltzman characterized the US cohort as a “pre-selected population,” reasoning that patients generally need to “walk through the door and have an interest in treatment” to be represented in an oncology-practice database. In that setting, treatment may be more common, he said.

The populations differed in other ways. The US study required at least two clinical visits after metastatic diagnosis, potentially favoring patients who remained engaged with the oncology system and making the cohort less representative of patients who had little or no subsequent oncology care.

Differences in patient preferences may also contribute. Saltzman noted that the 39% of Dutch patients who did not receive any systemic therapy based on patient and family preference is “very high” compared to patients he sees in his clinic. In the US, he said, most patients with good performance status want treatment, and even some with poorer performance status may be reluctant to forego it.

While the goal in metastatic pancreatic cancer is to help patients “live a bit longer and a bit better,” Saltzman said, longer survival with systemic therapy does not necessarily translate into better quality of life for every patient.

In the US, there can also be a tendency to treat “because it’s easier to treat than it is to talk to people about what their clear prognosis is,” Saltzman said.

The Dutch study had no specific funding. The US study was funded by Astellas Pharma Inc. Disclosure information for study authors is available with the original publications. Saltzman had no relevant disclosures.