Sequential therapy of refractory metastatic pancreatic cancer with 5-FU/LV/irinotecan (FOLFIRI) vs. 5-FU/LV/oxaliplatin (OFF). The PANTHEON trial (AIO PAK 0116)

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2024年7月1日

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Dominik Paul Modest,
Volker Heinemann,
Philipp Schütt,
Stefan Angermeier,
Mike Haberkorn,
Oliver Waidmann,
Ullrich Graeven,
Kai Wille,
Volker Kunzmann,
Larissa Henze,
Christian Constantin,
Maike de Wit,
Claudio Denzlinger,
Alexej Ballhausen,
Annika Kurreck,
Ivan Jelas,
Annabel Helga Sophie Alig,
Arndt Stahler,
Sebastian Stintzing,
Helmut Oettle

摘要

Purpose

In patients with metastatic pancreatic cancer, after failure of gemcitabine/nab-paclitaxel, this trial compares the efficacy of second-line therapy with FOLFIRI vs. OFF (1:1 randomisation) with cross-over to the vice-versa regimen as third-line therapy.

Patients and Methods

The primary endpoint was PFS (progression-free survival: time from randomization until progression or death) of second-line therapy. The trial aimed to demonstrate non-inferiority of FOLFIRI vs OFF (non-inferiority margin of a hazard ratio (HR) of 1.5, power of 80% and a significance level of 5%, 196 events needed). Secondary endpoints included overall survival (OS), progression-free survival of third-line therapy and safety. The trial is registered with EudraCT Nr. 2016–004640-11.

Results

The trial was terminated with 60 evaluable (37 with FOLFIRI, 23 with OFF) patients due to insufficient recruitment. PFS of second-line therapy was 2.4 (95% CI 2.3–2.6) months with FOLFIRI vs 2.4 (95% CI 2.2–2.7) months with OFF (HR: 0.80, 95% CI 0.45–1.42, P = 0.43). OS was comparable between the arms (HR: 0.95, 95% CI 0.54–1.66), P = 0.84). Only 4 out of 28 (14%) patients receiving third-line therapy achieved a disease control (partial remission or stable disease). Both second-line regimens were well tolerated without new or unexpected safety signals being observed.

Conclusion

The exploratory analysis of this early terminated trial suggests that FOLFIRI and OFF have similar efficacy ant toxicity as second-line therapy of PDAC after failure of gemcitabine/nab-paclitaxel. Third-line therapy regardless of regimen does not provide satisfactory efficacy in this sequential treatment algorithm.