Health-Related Quality of Life Analysis in Metastatic Colorectal Cancer Patients Treated by Second-Line Chemotherapy, Associated With Either Cetuximab or Bevacizumab: The PRODIGE 18 Randomized Phase II Study

Abstract Background and objectives : We have previously showed that for patients with wild-type RAS metastatic colorectal cancer (mCRC) progressing after bevacizumab plus chemotherapy, bevacizumab continuation plus a switch of chemotherapy is the most appropriate option (PRODIGE 18 phase II study). Here we aimed to determine treatment impact in patient's Health-Related Quality Of Life (HRQoL) in PRODIGE18 study. Methods : HRQoL was evaluated in two arms bevacizumab or cetuximab – combined with chemotherapy (modified FOLFOX6 [mFOLFOX6] or FOLFIRI) using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 at baseline, first and third tumour evaluation and at the end of the study. The temporal evolution of quality of life scores was investigated using longitudinal linear mixed models of variance. The time until definitive deterioration (TUDD) was estimated using the Kaplan-Meier method and the long-rank test. A univariate Cox model was used to calculate HR with 95% CI. A multivariate Cox model was applied to determine association of TUDD with age and gender. Safety was assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events. Results : HRQoL QLQ-C30 questionnaire compliance was high at baseline (>90%) and declined over time (∼ 70% in tumour evaluation 1 and ∼ 60% in tumour evaluation 3), but remained similar in both treatment arms. Patient reported mean diarrhoea QLQ-C30 score is significantly higher in bevacizumab treatment arm. Clinician reported mild diarrhoea was more frequently declared in bevacizumab treatment arm. Cox multivariate analyses showed no statistically significant differences in TUDD for all QLQ-C30 scales between treatments. TUDD of appetite loss was significantly associated to age. Conclusions : Our study shows that no relevant impairment of patients HRQoL between the two treatment arms. So, the analysis of the HRQoL with equal effectiveness does not make it possible to favor one treatment over another. ClinicalTrials.gov : NCT01442649; Clinicaltrialsregister.eu EUDRACT 2009-012942-22.