Predictive factors of severe early treatment-related toxicity in patients receiving first-line treatment for metastatic colorectal cancer: Pooled analysis of 2190 patients enrolled in Fédération Francophone de Cancérologie Digestive (FFCD) trials.

Aim: Few studies have explored the association between baseline characteristics and the occurrence of early toxicities in patients treated with first-line chemotherapy for metastatic colorectal cancer (mCRC).
Patients and Methods: Individual patient data of 2190 patients enrolled in 10 prospective FFCD (Fédération Francophone de Cancérologie Digestive) trials were analysed. Severe early toxicity was defined as the occurrence of grade ≥III toxicity within 3 months after initiation of chemotherapy (ET3).
Results: Patients received monotherapy based on 5-FU (n = 1068), a cytotoxic doublet (n = 395) or tritherapy with a cytotoxic doublet plus anti-VEGF agent or a cytotoxic triplet (n = 727). The patients received 5-FU (100%), Irinotecan (39.6%), Oxaliplatin (13.4%), Bevacizumab (29.6%) or Aflibercept (1.8%). ET3 occurred in 244 patients (22.8%) with monotherapy, 248 patients (62.8%) with doublet and 392 patients (53.9%) with tritherapy. The most frequent ET3s were related to biological abnormalities and/or gastrointestinal, general and vascular disorders. The prognostic factors for the occurrence of an ET3 in multivariate analysis were a performance status of 2 rather than 0-1 (OR 2.57; 95% CI [1.16, 5.73]; p = 0.02), tritherapy versus monotherapy (OR 2.31; 95% CI [0.84, 6.33]; p = 0.02), alkaline phosphatase > 300 UI/l (OR 3.07; 95% CI [1.79, 5.27]; p < 0.001) and non-resected primary tumour versus resection (OR 1.59; 95% CI [1.06, 2.39]; p = 0.02). Median overall survival in patients without ET3 was significantly longer than that in patients with ET3 (HR 0.87; 95% CI [0.80-0.96]; p = 0.004).
Conclusion: ET3 is frequent whatever the treatment regimen and is associated with certain baseline characteristics. The clinical impact of ET3 on prognosis in mCRC warrants further investigation.
Competing Interests: Conflict of interest statement CB, KLM, ADG and OB have no conflict of interest to declare. TA has received personal fees from AstraZeneca, Amgen, Servier, Bioven, Sanofi and Roche, and non-financial support from Bayer, Roche and Ipsen. MD has received personal fees from Amgen, AstraZeneca, Bayer, Merck Serono, Pierre Fabre, Roche, Servier, Lilly, Merck and Ipsen, and non-financial support from Roche, Merck Serono and Bayer. TL and TA have received personal fees from Amgen, Merck Serono, Servier and Sanofi, and non-financial support from Amgen. JBB has received personal fees from Amgen, AstraZeneca, Bayer, Merck Serono, Pierre Fabre, Roche, Sanofi, Servier and Shire, and non-financial support from Amgen, Merck Serono and Roche. JT has received personal fees from Amgen, Roche, Merck Serono, Pierre Fabre, MSD, Sanofi, Servier and Shire, and non-financial support from Amgen, Merck Serono and Roche. JLL has received personal fees from Novartis and Pfizer, and non-financial support from Servier, Novartis and Keocyt. JB has received personal fees from Amgen, AstraZeneca, Bayer, Merck Serono, Pierre Fabre, Roche, Sanofi, Servier and Shire, and non-financial support from Amgen, Merck Serono and Roche. OB has received personal fees or non-financial support from Amgen, Roche, Merck, Pierre Fabre, Servier, MSD, Bayer and Sanofi. SM has received non-financial support from Amgen, Roche, Servier, Astra Zeneca, Ipsen pharma, Novartis pharma, Bayer, MSD and Sirtex medical Europe. JMG has received personal fees from Amgen, Janssen Cilag, Sanofi, Takeda and Tillots Pharma).
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