Pancreatic Cancer: What the ESPAC-4 Randomized Adjuvant Chemotherapy Trial Tells Us

Researchers recently reported on patterns of recurrence after resection of pancreatic ductal adenocarcinoma. The results of their secondary analysis of the ESPAC-4 randomized adjuvant chemotherapy trial were published in JAMA Surgery.

The authors investigated rates and patterns of pancreatic cancer recurrence after resection and systemic adjuvant chemotherapy. Although some observations have been reported in the past, such patterns in the clinical setting of pancreatic ductal adenocarcinoma had not been thoroughly studied or documented, particularly in terms of survival.

Due to current prognoses and outcomes statistics, pancreatic cancer is widely regarded as a systemic cancer, regardless of metastases sites. This calls for systemic therapy after resection as an effective adjuvant treatment. This secondary analysis of a randomized clinical trial reexamined median recurrence-free survival, median survival after recurrence, sites of recurrence, and the median overall survival. Data was collected prospectively from the phase 3 European Study Group for Pancreatic Cancer 4 adjuvant clinical trial, The international multicenter study involved 730 pancreatic cancer patients who underwent resection followed by adjuvant chemotherapy. Participants were randomized to adjuvant gemcitabine or gemcitabine with capecitabine. Researchers analyzed the data from 2017 through 2019.

Results were similar to those in the original analysis. Compared with gemcitabine monotherapy, adjuvant gemcitabine with capecitabine correlated with a lower incidence of local recurrence and was associated with longer overall survival.
Median age of the 730 patients was 65 years (range 37-81 years); there were 414 men (57%), and 316 women (43%). From randomization, median follow-up time was 43.2 months (95% CI, 39.7-45.5 months), and overall survival from surgery was 27.9 months (95% CI, 24.8-29.9 months) with gemcitabine and 30.2 months (95% CI, 25.8-33.5 months) with the combination (HR, 0.81; 95% CI, 0.68-0.98; P = .03). The 5-year survival rates were 17.1% (95% CI, 11.6%-23.5%) and 28.0% (22.0%-34.3%), respectively. There were 479 patients (65.6%) who experienced recurrence. Local recurrence rates had a median of 11.63 months (95% CI, 10.05-12.19 months), while distant recurrence had a median of 9.49 months (95% CI, 8.44-10.71 months) (HR, 1.21; 95% CI, 1.01-1.45; P = .04). Median survival after recurrence was 9.36 months (95% CI, 8.08-10.48 months) for local recurrence and 8.94 months (95% CI, 7.82-11.17 months) for distant recurrence (HR, 0.89; 95% CI, 0.73-1.09; P = .27). Median OS in patients with only distant recurrence (23.03 months; 95% CI, 19.55-25.85 months) and for those with both local with distant recurrence (23.82 months; 95% CI, 17.48-28.32 months) was similar to those who had only local recurrence (24.83 months; 95% CI, 22.96-27.63 months) (P = .85 and P = .35, respectively). Of the 730 participants, 78 patients (10.7%) died without a recurrence. Compared with monotherapy (HR, 0.79; 95% CI, 0.64-0.98; P = .03), gemcitabine with capecitabine showed a 21% reduction in mortality after recurrence.