Chemo is it.

Top Line: The recently reported Alliance A021501 trial points to neoadjuvant FOLFIRINOX as the best first step for borderline resectable pancreatic cancer.

The Study: ESPAC-5 is now here to further cement this approach. It enrolled and analyzed 86 patients with borderline resectable pancreatic cancer treated across 16 centers in the UK and France. Of note, even with so many institutions participating, it took over 4 years to fail to enroll a goal of 100 patients, highlighting the difficulty of overcoming patient and provider preference when attempting to randomize across very different treatment schemas. They were randomized to one of four arms: [1] immediate surgery, [2] neoadjuvant weekly gemcitabine and daily capecitabine per ESPAC-4 x 8 weeks, [3] neoadjuvant FOLFIRINOX q2 weeks per Alliance x 4 for 8 weeks, [4] or neoadjuvant chemoradiation to 50.4 Gy in 28 fractions with concurrent capecitabine over 5.5 weeks. After enrollment, only 21 of 31 patients (68%) actually received surgery in the immediate surgery group. Of the remaining patients, 40 of 55 (80%) completed their assigned neoadjuvant therapies, and 30 of 55 (55%) underwent subsequent resection. At one year, there was a significant discrepancy in survival rate across arms: [1] 39% after immediate surgery, [2] 78% after neoadjuvant gemcitabine + capecitabine, [3] 84% after neoadjuvant FOLFIRINOX, and [4] 60% after neoadjuvant chemoradiation.

TBL: “Accepting the limitations of small patient numbers and a short follow-up time, the results of ESPAC5 show that neoadjuvant short-course combination chemotherapy was more effective than immediate surgery with adjuvant therapy in the setting of borderline resectable pancreatic ductal adenocarcinoma, and favoured neoadjuvant chemotherapy rather than neoadjuvant chemoradiotherapy. | Ghaneh, Lancet Gastroenterol Hepatol 2022