The regimen did not affect survival in node negative patients

Adjuvant chemotherapy prolonged survival in patients with node-positive pancreatic cancer initially treated with neoadjuvant FOLFIRINOX followed by surgical resection, an international retrospective cohort study found.

In contrast, adjuvant chemotherapy did not affect survival in patients with node-negative pancreatic cancer who were treated with the same initial neoadjuvant/surgical regimen, Marc Besselink, MD, PhD, Amsterdam University Medical Center, University of Amsterdam, The Netherlands, and colleagues from the European-African Hepato-Pancreato-Biliary Association reported in JAMA Oncology.

For the entire cohort of 520 patients, adjuvant therapy did not improve median overall survival (OS) at 29 months (95% CI, 26-36 months) for both those who received additional adjuvant treatment and those who did not (95% CI, 24-45 months), researchers noted. However, on multivariate analysis, patients with pathology-proven node-positive (ypN+) disease treated with adjuvant chemotherapy had a 59% improvement in OS at a Hazard Ratio (HR) of 0.41 (95% CI, 0.22-0.75; P=0.004), the study group reported.

In this subgroup of patients, median OS survival was 26 months (95% CI, 22-32 months) for those who received additional chemotherapy compared with 13 months (95% CI, 9-20 months) for patients who did not. This compared to a median OS of 38 months (95% CI, 31 months to not reached) in the adjuvant node-negative (ypN−) subgroup compared with 54 months (95% CI, 34 months to not reached) in the ypN− subgroup who did not receive adjuvant therapy.

Roughly half of the cohort was made up of patients with ypN+ disease while the remaining half consisted of ypN− patients.

“The benefit of adjuvant chemotherapy after resection of pancreatic cancer following neoadjuvant combination treatment with folinic acid, fluorouracil, irinotecan and oxaliplatin (FOLFIRINOX) is unclear,” Besselink and colleagues observe.

“The present study suggests that only the subgroup of patients with ypN+ resected pancreatic cancer after neoadjuvant FOLFIRINOX benefited from adjuvant treatment,” they concluded.

All patients underwent pancreatic surgery after receiving at least 2 cycles of neoadjuvant FOLFIRINOX between January 2012 and December 2018. No patient had metastatic pancreatic cancer. The median age of the patients in the study was 61 years (Interquartile range (IQR), 53-66 years) and slightly over half (54%) were male.

The pancreatic cancer was staged as resectable in 48.4% of the cohort; as borderline resectable pancreatic cancer (BRPC) in 41.4% of patients, and as locally advanced pancreatic cancer (LAPC) in 10.2% of patients. Stage was unknown in a small fraction of the cohort.

Treatment with neoadjuvant FOLFIRINOX consisted of oxaliplatin at a dose of 85 mg/m2222, given every 2 weeks.

This was followed by either pancreatoduodenectomy, distal pancreatectomy, or total pancreatectomy.

The median number of neoadjuvant FOLFIRINOX cycles at 6 was the same for patients who received adjuvant therapy and those who did not. Almost two-thirds of the cohort at 66% received adjuvant chemotherapy, the authors pointed out. More patients at approximately 59% received a gemcitabine-based adjuvant regimen, but almost 20% of patients again received adjuvant FOLFIRINOX, they noted.

Approximately 4% of patients received capecitabine while 13% were treated with a combination of other chemotherapeutic agents.

At a median follow-up of 35 months (IQR, 22-44 months), median OS for the entire cohort was 38 months (95% CI, 36-46 months) after patients had been diagnosed with pancreatic cancer and 31 months (95% CI, 29-37 months) after they had undergone surgery.

“When patients were stratified for different types of adjuvant therapy, a benefit was found for both adjuvant gemcitabine and adjuvant FOLFIRINOX in the ypN+ group, with a larger benefit of adjuvant FOLFIRINOX,” investigators noted.

Specifically, median OS in the node-positive subgroup was 27 months (95% CI, 21-34 months) for those who received adjuvant gemcitabine and 28 months (23 months to not reached) for their FOLFIRINOX counterparts versus only 13 months (95% CI, 9-20 months) for those who did not receive either gemcitabine or FOLFIRINOX adjuvant therapy.

“Adjuvant therapy remained associated with improved survival in subgroup analysis of patients with ypN1 or ypN2 disease and for both FOLFIRINOX and gemcitabine-based adjuvant therapy,” Besselink and colleagues noted.

“This effect modification by nodal status was most expressed in BRPC and LAPC and diminished after an increasing number of preoperative cycles of FOLFIRINOX,” they added.

The authors acknowledged that it is possible oncologists were more prone to give adjuvant treatment to fitter patients and less likely to give it to those with poor prognostic features, which would potentially overestimate the effect that adjuvant therapy had on patient outcomes.

However, in this study, those who received adjuvant chemotherapy more often had unfavorable tumor features on pathology, potentially underestimating the effect of adjuvant therapy, as investigators observed.

Limitations to the study include the fact that data were retrospectively collected by 31 centers in 19 countries and heterogeneity of the data cannot be ruled out.

The cohort also included only highly selected patients and did not include those who either progressed on neoadjuvant chemotherapy or who underwent surgical exploration but not resection.

  1. Adjuvant chemotherapy prolonged survival in patients with node-positive, though not node-negative, pancreatic cancer following neoadjuvant FOLFIRINOX and surgical resection.

  2. Additional FOLFIRINOX was associated with greater benefit compared with adjuvant gemcitabine but again only in node-positive pancreatic cancer patients.

Pam Harrison, Contributing Writer, BreakingMED™

Besselink had no conflicts of interest to declare.

Cat ID: 120

Topic ID: 78,120,730,120,192,925