METAPANC, intensified treatment in patients with oligometastatic pancreatic cancer: Multimodal surgical treatment versus systemic chemotherapy alone—A prospective randomized controlled multicenter phase III trial.

TPS4207 Background: Pancreatic ductal adenocarcinoma (PDAC) has a dismal overall survival rate due to early metastasis and high therapy resistance. The successful introduction of intensified chemotherapeutic regimen such as FOLFIRINOX (FFX) has significantly increased response rates, disease control and overall survival. Current standards recommend systemic chemotherapy but no surgical approach in metastatic PDAC. FFX has the highest rates of response and overall survival and is a current standard of care in patients with metastatic PDAC and good performance status. Extensive surgical interventions with synchronous or metachronous metastasectomy is not recommended according to current guidelines. Retrospective data suggest beneficial outcomes in patients with hepatic oligometastasis, though prospective data from randomized clinical trials are not available. Methods: METAPANC is a prospective randomized controlled multicenter phase III trial evaluating survival and quality of life after multimodal therapy with perioperative modified FOLFIRINOX (mFFX) chemotherapy (two times 4 cycles prior to resection of the primary tumor and resection of the metastases), followed by 4 cycles of adjuvant mFFX chemotherapy (Arm A) vs. mFFX (without surgery), as standard of care first-line treatment (Arm B). Patients are eligible for randomization after 8 cycles of mFFX if they have at least stable disease on imaging according to RECIST V1.1 (Response Assessment I after 4 cycles and Response Assessment II after 8 cycles of mFFX). Patients with progressive disease will be excluded from the study. This clinical trial will focus on a well-defined patient collective with resectable PDAC and metastatic load limited to the liver with a maximum of three metastases. Patients with metachronous liver metastatic status can also be included, but must have completed adjuvant chemotherapy at least 6 months before start of study treatment. In patients randomized into Arm A with metastatic lesions located in the center of the liver local ablative techniques can be combined. In total 272 patients will be enrolled and will be randomized 1:1. The primary endpoint is overall survival, secondary endpoints are progression free survival, procedure related complications and mortality, quality of life, quality-adjusted time without symptoms and toxicity. METAPANC is accompanied by an exploratory biomarker analysis program of collecting biological and imaging samples to subsequently identify and evaluate molecular-based patient subgroups and biomarkers for identification of a potential target population which may benefit from the intensified multimodal treatment strategy. 22 German participating sites are selected. Further international sites are planned in the Netherlands, Norway, Finland and Sweden. Clinical trial information: 2023-503558-10-00.