Abstract 1301P
Background
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.
Methods
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.
Results
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%).
Conclusions
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.
Clinical trial identification
EudraCT 2016-004640-11.
Editorial acknowledgement
Legal entity responsible for the study
AIO Studien gGmbH.
Funding
AIO Studien gGmbH and Celgene (Bristol Myers Squibb GmbH & Co. KGaA).
Disclosure
D.P. Modest: Financial Interests, Personal, Invited Speaker, Advisory Boards: Amgen, Servier, G1, Transgene, Merck, Onkowissen, BMS, MSD, Takeda, Pierre Fabre, Lilly, Sanofi, AstraZeneca; Financial Interests, Institutional, Research Grant: Amgen, Servier. V. Heinemann: Financial Interests, Personal, Invited Speaker: merck, Amgen, roche, Sanofi, SIRTEX, Servier, Pfizer, Pierre Fabre, AstraZeneca, BMS, MSD, Novartis, Boehringer- ingelheim, Celgene, Terumo, Oncosil; Financial Interests, Institutional, Research Grant: Amgen, Merck, Roche, Sanofi, Pfizer, Boehringer-Ingelheim, Sirtex, Servier. O. Waidmann: Financial Interests, Personal, Invited Speaker: Amgen, Bayer, BMS, Celgene, Eisai, Incyte, Ipsen, Merck Serono, MSD, Novartis, Roche, Servier, Amgen, AstraZeneca, Bayer, BMS, Eisai, Ipsen, MSD, Novartis, Roche; Financial Interests, Personal, Sponsor/Funding, Travel support: AbbVie, Bayer, BMS, Gilead, Ipsen, Medac, Merck; Financial Interests, Institutional, Research Grant: Merck. U. Graeven: Financial Interests, Invited Speaker: Amgen, Boehringer Ingelheim, AstraZeneca, BMS, MSD, Sanofi, Novartis; Financial Interests, Stocks/Shares: Biontech. C. Denzlinger: Financial Interests, Invited Speaker: AbbVie, Bayer, Celgene, Incyte, Janssen, Novartis. A.H.S. Alig: Financial Interests, Invited Speaker: MSD. A. Stahler: Financial Interests, Personal, Invited Speaker: Roche, Servier, Taiho, Amgen, Pfizer, Lilly, Merck. S. Stintzing: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Bayer, BMS, MSD, Esai, Leo Pharma, Lilly, Merck, Pierre Fabre, Roche, Sanofi, Servier, Taiho, Takeda; Financial Interests, Institutional, Research Grant: Merck, PierreFabre, Servier, Roche, Amgen. H. Oettle: Financial Interests, Project Lead: BMS, Servier. All other authors have declared no conflicts of interest.