Neoadjuvant Chemotherapy Associated With Improved OS in Borderline Resectable Pancreatic Cancer

Treatment with neoadjuvant modified FOLFIRINOX (mFOLFIRINOX) alone was associated with favorable overall survival (OS) among patients with borderline resectable pancreatic ductal adenocarcinoma compared to treatment with mFOLFIRINOX plus hypofractionated radiotherapy, according to a phase 2 trial.

The multicenter, phase 2 trial enrolled 126 patients with pancreatic ductal adenocarcinoma confirmed to be borderline resectable who had not previously been treated with chemotherapy or radiation between February 2017 and January 2019. Patients were randomized to either arm 1 (n = 70) or arm 2 (n = 56). Arm 1 received 8 cycles of mFOLFIRINIOX (oxiplatin, irinotecan, leucovorin followed by fluorouracil infusion) over 46 hours every 2 weeks. Arm 2 received 7 cycles of the mFOLFIRINOX treatment, followed by either stereotactic body radiation therapy or hypofractionated image-guided radiation therapy.

Those patients without disease progression in either arm then underwent pancreatectomy, followed by 4 cycles of FOLFOX6 (oxaliplatin, leucovorin, bolus 5-fluorouracil, and 5-fluorouracil infusion). The primary end point of the study was the 18-month OS rate. Secondary end points included event-free survival (EFS) and safety.

At the interim analysis, arm 2 was closed, as it did not meet the statistical requirements to conclude efficacy while arm 1 continued enrollment to completion.

The median follow-up duration was 42.9 months (95% confidence interval [CI], 39.7 to 43.4). The 18-month OS was 66.7% in arm 1 (95% CI, 56.1% to 79.4%), compared to 47.3% in arm 2 (95% CI, 35.8% to 62.5%). The median OS was 29.8 months for arm 1 (95% CI, 21.1 to 36.6) and 17.1 months for arm 2 (95% CI, 12.8 to 24.4). The median EFS was 15 months (95% CI, 11.2 to 21.9).

Treatment was well-tolerated, with 57% and 64% of patients experiencing 1 or more grade ≥3 adverse event that could possibly be related to treatment in arm 1 and arm 2, respectively. The most common grade ≥3 adverse events possibly related to treatment during treatment with FOLFIRINOX were diarrhea (18%), hypokalemia (14%), and neutropenia (12%). The most common grade ≥3 adverse event during radiotherapy was anemia (5%).

“The results of this randomized clinical trial suggest that mFOLFIRINOX represents a reference neoadjuvant treatment regimen for borderline resectable pancreatic cancer; however, the role of radiotherapy in this setting remains undefined,” concluded the study authors.

Source:

Katz MH, Shi Q, Meyers J, et al. Efficacy of preoperative mFOLFIRINOX vs mFOLFIRINOX plus hyperfractionated radiotherapy for borderline resectable adenocarcinoma of the pancreas: The A021501 phase 2 randomized clinical trial. JAMA Oncol. Published online July 14, 2022. doi:10.1001/jamaoncol.2022.2319