OBJECTIVES: PETACC-1 assessed if raltitrexed is non-inferior to 5-fluorouracil and leucovorin for relapse-free survival (RFS) and overall survival (OS) in adjuvant stage III colon cancer. METHODS: Non-inferiority required both HR for RFS and OS<1.25 at 1-sided alpha=0.05. Patients (1921) were randomised to six cycles of 5-FU/LV (n=969) or eight cycles of raltitrexed (n=952). We report the final results in 993 eligible patients who started and completed the allocated treatment (489 5-FU/LV and n=504 Raltitrexed) of whom respectively 146 and 148 died, respectively. RESULTS: The trial closed prematurely when 17 (1.9%) raltitrexed-related deaths were reported. Haematological and gastrointestinal toxicities were more frequent with 5-FU/LV, liver toxicities with raltitrexed. Raltitrexed was stopped for toxicity in 13.2% and 5-FU/LV in 8.5%. Sixty-day mortality was 9% versus 7%. With 4.1 years median follow-up, the HR for RFS was 1.16 (90% CI 0.99-1.37) and that for OS was 1.01 (90% CI 0.84-1.23). CONCLUSION: The trial failed to demonstrate non-inferiority of raltitrexed. FUNDING: Free drugs and financial support from AstraZeneca.
RCT Entities:
OBJECTIVES: PETACC-1 assessed if raltitrexed is non-inferior to 5-fluorouracil and leucovorin for relapse-free survival (RFS) and overall survival (OS) in adjuvant stage III colon cancer. METHODS: Non-inferiority required both HR for RFS and OS<1.25 at 1-sided alpha=0.05. Patients (1921) were randomised to six cycles of 5-FU/LV (n=969) or eight cycles of raltitrexed (n=952). We report the final results in 993 eligible patients who started and completed the allocated treatment (489 5-FU/LV and n=504 Raltitrexed) of whom respectively 146 and 148 died, respectively. RESULTS: The trial closed prematurely when 17 (1.9%) raltitrexed-related deaths were reported. Haematological and gastrointestinal toxicities were more frequent with 5-FU/LV, liver toxicities with raltitrexed. Raltitrexed was stopped for toxicity in 13.2% and 5-FU/LV in 8.5%. Sixty-day mortality was 9% versus 7%. With 4.1 years median follow-up, the HR for RFS was 1.16 (90% CI 0.99-1.37) and that for OS was 1.01 (90% CI 0.84-1.23). CONCLUSION: The trial failed to demonstrate non-inferiority of raltitrexed. FUNDING: Free drugs and financial support from AstraZeneca.
Authors: Romain Cohen; Dewi Vernerey; Carine Bellera; Aurélia Meurisse; Julie Henriques; Xavier Paoletti; Benoît Rousseau; Steven Alberts; Thomas Aparicio; Ioannis Boukovinas; Sharlene Gill; Richard M Goldberg; Axel Grothey; Tetsuya Hamaguchi; Timothy Iveson; Rachel Kerr; Roberto Labianca; Sara Lonardi; Jeffrey Meyerhardt; James Paul; Cornelis J A Punt; Leonard Saltz; Marck P Saunders; Hans-Joachim Schmoll; Manish Shah; Alberto Sobrero; Ioannis Souglakos; Julien Taieb; Atsuo Takashima; Anna Dorothea Wagner; Marc Ychou; Franck Bonnetain; Sophie Gourgou; Takayuki Yoshino; Greg Yothers; Aimery de Gramont; Qian Shi; Thierry André Journal: Eur J Cancer Date: 2020-03-12 Impact factor: 9.162