1301P Sequential therapy of metastatic pancreatic ductal adenocarcinoma (PDAC) after failure of gemcitabine plus nab-paclitaxel with either 5-FU/folinic acid (5FU/LV) plus irinotecan (FOLFIRI) followed by 5FU/LV plus oxaliplatin (OFF) or the reverse sequence: The PANTHEON trial (AIO PAK 0116)

Abstract

After failure of first-line systemic therapy of PDAC with gemcitabine/nab-paclitaxel established treatment options are usually based on fluoropyrimidines, either in combination with (nanoliposomal) irinotecan (NAPOLI/FOLFIRI) or with oxaliplatin (i.e. OFF). The PANTHEON-trial aims to investigate the efficacy of second-line therapy with FOLFIRI vs OFF with cross-over to the vice-versa regimen after failure of second-line therapy. The trial randomized FOLFIRI vs. OFF in a 1:1 fashion. The primary endpoint was PFS (progression-free survival: time from randomization until progression or death) of second-line therapy. The trial was designed to demonstrate non-inferiority of FOLFIRI vs. OFF. With a non-inferiority margin of a hazard ratio (HR) of 1.5, power of 80% and a significance level of 5%, it was intended to recruit 204 patients to observe 196 events. Secondary endpoints included overall survival (OS), progression-free survival of 3rd-line therapy as well as time to failure of strategy and safety. The trial is registered with EudraCT Nr. 2016-004640-11. The trial was terminated with 59 evaluable (36 with FOLFIRI, 23 with OFF) patients due to insufficient recruitment. PFS of second-line therapy was 2.5 (95% CI 2.4-4.7) months with FOLFIRI vs. 2.4 (95% CI 2.0-3.0) months with OFF (HR: 0.71, 95% CI 0.40-1.28, P=0.26). OS was 6.5 (95% CI 4.7-10.3) months with FOLFIRI vs. 6.0 (95% CI 4.7-10.0) months with OFF (HR: 0.89, 95% CI 0.51-1.56), P=0.70). Third-line therapy was given in 17 of 36 patients (47%) and 10 of 23 (43%) patients, respectively. Adverse events of grade 3-5 were observed in 15/36 patients in the FOFIRI arm (42%) vs. 11/23 patients in the OFF arm (48%). The exploratory analysis of this early terminated trial suggests that FOLFIRI and OFF have similar efficacy as second-line therapy of PDAC after failure of gemcitabine/nab-paclitaxel. The frequency of patients receiving crossover third-line therapy and the frequency of grade 3-5 events were also comparable.