Does Adjuvant Chemotherapy Help After Preoperative FOLFIRINOX in Pancreatic Cancer?

Why This Matters

• Pancreatic adenocarcinomais a cancer with limited treatment options. Surgery is currently the only curative treatment—one capable of achieving a complete cure—for pancreatic cancer.
• Only 15-20% of patients have operable disease at diagnosis. Even among these patients, however, recurrence risk is high.
• To improve surgical outcomes, systemic chemotherapy is used before surgery (neoadjuvant) and after surgery (adjuvant).
• Although neoadjuvant FOLFIRINOX has improved pancreatic cancer outcomes, the effectiveness of adjuvant treatment has not been fully established.

A study published on January 23, 2025, in JAMA Oncology examined the effects of adjuvant chemotherapy on overall survival in detail. Its findings could help shape pancreatic cancer treatment algorithms.

The JAMA Study Finds That Adjuvant Chemotherapy Improves Survival

• Among patients receiving preoperative FOLFIRINOX followed by surgical resection for pancreatic adenocarcinoma, postoperative FOLFIRINOX or other multiagent chemotherapy regimens significantly improved overall survival.

• Postoperative FOLFIRINOX reduces mortality risk by 34% in pancreatic cancer patients. Multiagent treatment provides up to a 43% improvement in survival.

• Single-agent adjuvant chemotherapy showed no significant survival benefit.

Study Design

The retrospective cohort study examined patients with localized pancreatic adenocarcinoma treated between 2010-2018 at 48 centers in 20 countries.

Among the 767 patients included:

• Median age: 62 years (interquartile range: 55-67 years).

• 52.7% were men.

Patients received 2-11 cycles of preoperative FOLFIRINOX followed by surgical resection.

The primary outcome was overall survival (OS), calculated from month 3 after surgery.

Results: The Effect of Adjuvant Chemotherapy

• Adjuvant chemotherapy independently prolonged overall survival (OS). Receiving adjuvant chemotherapy was associated with a 34% reduction in mortality risk (HR: 0.66; 95% CI: 0.49-0.87).

• Adjuvant FOLFIRINOXimproved survival by reducing mortality risk by 43% (HR: 0.57; 95% CI: 0.40-0.80). Similarly, other multiagent chemotherapy regimens extended survival by 39% (HR: 0.61; 95% CI: 0.41-0.92).

• However, single-agent adjuvant chemotherapy had no significant effect on survival. Although mortality risk fell with single-agent treatment, the reduction was not statistically significant (HR: 0.75; 95% CI: 0.55-1.03).

The image above presents two Kaplan–Meier plots comparing overall survival with adjuvant therapy (AT) regimens in pancreatic adenocarcinoma.

• Panel A (Left Plot): Compares overall survival between the AT (adjuvant therapy) and no-AT groups. Overall survival is markedly higher among patients receiving adjuvant treatment.
• Panel B (Right Plot): Compares different adjuvant regimens. (m)FOLFIRINOX and other multiagent regimens improved survival more than single-agent treatment or no treatment.

The effect of adjuvant chemotherapy on survival was less pronounced when:

• Eight or more cycles of neoadjuvant FOLFIRINOX had been given,

• A radiological response had occurred,

• There was no lymph node involvement (ypN0 disease).

Clinical Practice: Treatment Options and Considerations

The researchers emphasized caution when multiagent adjuvant chemotherapy is not possible, weighing treatment burden against the possibility that single-agent treatment may offer no benefit. They also noted that the number of neoadjuvant cycles may affect adjuvant treatment effectiveness.

Study Limitations

• The reasons for choosing adjuvant treatment other than FOLFIRINOX, or no adjuvant treatment, are unknown, potentially introducing selection bias.

• The relationship between neoadjuvant cycle counts and adjuvant regimens could not be analyzed in detail.

• Some clinicopathological parameters were excluded because more than 20% of data were missing.

Commentary

This study strongly supports improved overall survival with multiagent adjuvant chemotherapy in pancreatic adenocarcinoma patients receiving preoperative FOLFIRINOX. However, the limited benefit of single-agent treatment highlights the need for careful assessment during treatment planning.