EClinicalMedicine (Jan 2025)

Panitumumab plus 5-fluorouracil and folinic acid or 5-fluorouracil and folinic acid alone as maintenance therapy in RAS wild-type metastatic colorectal cancer (PanaMa, AIO KRK 0212): final efficacy analysis of a randomised, open-label, phase 2 trialResearch in context

  • Arndt Stahler,
  • Meinolf Karthaus,
  • Stefan Fruehauf,
  • Ullrich Graeven,
  • Lothar Müller,
  • Ludwig Fischer von Weikersthal,
  • Karel Caca,
  • Eray Goekkurt,
  • Alexej Ballhausen,
  • Greta Sommerhäuser,
  • Annabel H.S. Alig,
  • Swantje Held,
  • Armin Jarosch,
  • David Horst,
  • Anke Reinacher-Schick,
  • Stefan Kasper,
  • Volker Heinemann,
  • Sebastian Stintzing,
  • Tanja Trarbach,
  • Dominik P. Modest

Journal volume & issue
Vol. 79
p. 103004

Abstract

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Summary: Background: The PanaMa trial aimed to compare the efficacy of 5-fluorouracil and folinic acid (FU/FA) ± panitumumab maintenance in untreated RAS wild-type metastatic colorectal cancer (mCRC) patients. Methods: In this final phase 2 trial analysis, adult mCRC patients responding to six cycles of FU/FA, oxaliplatin and panitumumab were randomized (1:1, open-label) to maintenance of either FU/FA + panitumumab or FU/FA alone. The primary endpoint was superiority of progression-free survival of maintenance (PFS; time from random assignment to progression/death) in favour of FU/FA + panitumumab. Secondary endpoints included PFS of re-induction (PFS re-ind.), time to failure of strategy (TFS) and overall survival (OS). The trial is registered with ClinicalTrials.gov (NCT01991873). Findings: In 248 patients of the Full Analysis Set recruited between May 2014 and February 2021, with a median observation of 64.0 (range 12.5–86.3) months and 59.7 (range 3.7–97.3) months in the treatment arms, 230 events for PFS (92.7%) and 196 events for OS (79.0%) were recorded. Adding panitumumab to FU/FA resulted in significantly longer PFS (8.8 versus 5.8 months, HR = 0.73 (95% CI 0.56–0.94), P = 0.015), shorter PFS re-ind. (4.1 versus 7.4 months, HR = 1.93 (95% CI 1.33–2.82), P < 0.001), comparable TFS (17.1 versus 15.7 months, HR = 0.98 (95% CI 0.68–1.42), P = 0.92) and numerically longer OS (29.9 versus 24.7 months, HR = 0.85 (95% CI 0.64–1.12), P = 0.24). The most frequent adverse event (AE) grade ≥3 was rash (FU/FA + panitumumab: n = 15, 12.0%, FU/FA: n = 17, 6.9%). 141 patients (37.3%) experienced at least one serious AE One treatment-related death occurred (neutropenic sepsis, FU/FA). Interpretation: Panitumumab plus FU/FA might be considered a standard of care maintenance regimen since a potential re-induction therapy with panitumumab cannot be guaranteed at the time of maintenance treatment decision. Funding: Amgen.

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