A phase III randomized clinical trial of Gemcitabine and Nab-Paclitaxel as switch maintenance versus continuation of modified FOLFIRINOX as first-line chemotherapy in patients with advanced pancreatic cancer: The PANThEON Study

Abstract

Background: Advanced pancreatic ductal adenocarcinoma (PDAC) remains among the most lethal cancers, with >95 % of patients dying from the disease. Chemotherapy is the standard of care in advanced stages, with FOLFIRINOX and Gemcitabine-Nab-Paclitaxel (Gem-NabP) as the main first-line regimens. Both show moderate efficacy and significant toxicity. Except for the PASS-01 trial, no direct comparison exists, though observational studies suggest that specific subgroups may benefit differently. Given the modest outcomes and rapid clinical decline, most patients are ineligible for second-line therapy after progression. The PANThEON study evaluates whether switching from modified FOLFIRINOX (mFOLFIRINOX) to Gem-NabP after three months of induction with mFOLFIRINOX improves outcomes for PDAC.

Methods: PANThEON is a no-profit, phase III, randomized, open-label, multicenter trial. The primary endpoint is overall survival (OS). Secondary endpoints include progression-free survival (PFS), time to treatment failure (TTF), overall response rate (ORR), and quality of life (QoL). Exploratory analyses will assess tumor profiling, circulating tumor DNA (ctDNA), and radiomics to identify predictive markers. A total of 220 patients will be randomized 1:1 to Gem-NabP (arm B) or continued mFOLFIRINOX (arm A).

Discussion: The PANThEON trial addresses two challenges: improving efficacy while reducing toxicity. Switching to Gem-NabP may enhance tolerability without compromising benefit, prolonging survival and refining PDAC treatment strategies.

Trial registration: PANThEON is registered at ClinicalTrials.gov (NCT06897644) and EuCT (2024-515214-41-00).

Keywords: Chemotherapy; Clinical trial; Gemcitabine plus Nabpaclitaxel; Pancreatic cancer; Switch maintenance; mFOLFIRINOX.