Abstract 443P
Background
In case of contraindication to fluoropyrimidines, raltitrexed is a validated alternative in metastatic colorectal cancer (mCRC), associated or not with oxaliplatin. Little is known about the outcomes of raltitrexed combined with irinotecan or targeted therapy.
Methods
This retrospective multicentre study enrolled mCRC patients treated with first-line raltitrexed-based chemotherapy. Treatment related toxicities were registered according to the NCI-CTC AE v4.0. Progression-free survival (PFS) and overall survival (OS) were calculated from treatment start.
Results
74 patients treated between 2005 and 2019 were included from 14 centres, with a median age of 69 years, 68% of men. The different regimens were: raltitrexed (n=8), TOMOX (n=40), TOMIRI (n=8), raltitrexed bevacizumab (n=1), TOMOX bevacizumab (n=12), TOMIRI bevacizumab (n=4) and TOMOX panitumumab (n=1). Reasons for prescribing raltitrexed were: fluoropyrimidine-induced cardiac toxicities (50%), cardiovascular comorbidities (24%) and dihydropyrimidine dehydrogenase deficiency (8%). 31% of patients had grade 3-4 side effects, regardless of the addition of bevacizumab (29% vs 32% without). After a median follow-up of 51.3 months (mo), median PFS was 9.9 mo (95%CI 7.9-13.1) and median OS was 28.3 mo (95%CI 25.1-38.1). Considering only the chemotherapy protocol, TOMOX was significantly associated with better objective response rate (ORR), PFS and OS compared to TOMIRI and raltitrexed with an ORR of 64%, 30% and 0% respectively (p=0.001), median PFS of 11.6 mo, 5.2 mo and 2.4 mo respectively (p < 0.0001) and median OS of 34.9 mo, 28.7 mo and 12.6 mo respectively (p=0.01). There was a trend to improve ORR, PFS and OS when bevacizumab was added to chemotherapy with an ORR of 59% vs 49% (p=0.48), median PFS of 15.2 mo vs 9 mo (p=0.6) and median OS of 37.6 mo vs 27.2 mo (p=0.3).
Conclusions
In patients with mCRC, first-line raltitrexed-based chemotherapy with or without targeted therapy had an acceptable safety profile. PFS and OS are consistent with the usual survival data in mCRC, and were significantly better in patients treated with TOMOX compared to TOMIRI, independently of targeted therapy. There was a trend to improve these outcomes with the addition of bevacizumab to chemotherapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
AGEO.
Funding
Has not received any funding.
Disclosure
C. Gallois: Honoraria (self): Servier, Sanofi Genzyme; Travel/Accommodation/Expenses: Amgen. E. Auclin: Travel/Accommodation/Expenses: Mundipharma; Honoraria (institution): Sanofi Genzymes. C. Coutzac: Honoraria (institution): Servier, Amgen; Travel/Accommodation/Expenses: Servier, Bayer, Amgen, Mundipharma. A. Turpin: Honoraria (self): Servier; Advisory/Consultancy: Mylan, Merck Sereno, Amgen; Travel/Accommodation/Expenses: Merck, Sanofi, Pfizer, AstraZeneca. C. Locher: Honoraria (self): merck, novartis ; Travel/Accommodation/Expenses: roche, ipsen, amgen. V. Hautefeuille: Honoraria (self): AAA, Amgen, Sanofi, Novartis, Servier, Ipsen; Travel/Accommodation/Expenses: Amgen, Sanofi, Ipsen, Pfizer, Merck, Bayer; Advisory/Consultancy: Amgen, Novartis, Ipsen. O. Dubreuil: Honoraria (self): Servier, Amgen, Merck-Serono, Roche, Sanofi; Advisory/Consultancy: Merck Serono, Amgen; Travel/Accommodation/Expenses: Servier, Amgen, Merck-Serono, Roche, Sanofi, MSD. L-J. Palmieri: Honoraria (self): Servier, Amgen, Merck, Keocyt. M. Dior: Honoraria (self): Servier, Roche, Merck. J. Taieb: Advisory/Consultancy: Lilly, Celgene, Shire, Servier, Merck KGaA, Sanofi, Roche Genentech, Pfizer and Amgen. All other authors have declared no conflicts of interest.