Quality of Life in Vulnerable Older Patients with Metastatic Colorectal Cancer Receiving Palliative Chemotherapy—The Randomized NORDIC9-Study

Abstract

Simple Summary Bowel cancer is one of the leading cancer-types in both sexes worldwide. Despite that most new cases and deaths occur in people aged 70 years or older, few clinical trials have investigated the best way to administer chemotherapy in older or frail patients. The NORDIC9-study established that moderately dose-reduced combination chemotherapy improved survival without extra side-effects compared to full dose single drug therapy. However, many older patients with incurable cancer seem to prefer preserved quality of life rather than longer survival. Therefore, our aim with the current quality of life analysis of the NORDIC9-study was to assess that the more effective chemotherapy was not at the expense of decreased quality of life. Our analyses showed that moderately dose-reduced combination chemotherapy-maintained quality of life, physical functioning, and resulted in less symptoms than treatment with full dose single drug in older patients not tolerating standard combination chemotherapy usually provided to young and fit patients. Abstract Quality of life data from randomized trials are lacking in older patients with metastatic colorectal cancer (mCRC). In the randomized NORDIC9-study, reduced-dose S1+oxaliplatin (SOx) showed superior efficacy compared to full-dose S1 monotherapy. We hypothesized that treatment with SOx does not result in inferior quality of life. Patients with mCRC aged ≥70 years and that were not a candidate for standard combination chemotherapy were included and randomly assigned to receive either S1 or SOx. The EORTC QLQ-C30 questionnaire was completed at baseline, after 9, and 18 weeks. The primary endpoint was global Quality of Life (QoL) at 9 weeks. For statistical analysis, a non-inferiority design was chosen applying linear mixed effects models for repeated measurements. The results were interpreted according to statistical significance and anchor-based, clinically relevant between-group minimally important differences (MID). A total of 160 patients aged (median (Interquartile range (IQR))) 78 years (76–81) were included. The QLQ-C30 questionnaire was completed by 150, 100, and 60 patients at baseline, at 9, and 18 weeks, respectively. The difference at 9 weeks in global QoL was 6.85 (95%CI—1.94; 15.65) and 7.37 (0.70; 14.05) in the physical functioning domain in favor of SOx exceeding the threshold for MID. At 18 weeks, the between-group MID in physical functioning was preserved. Dose-reduced combination chemotherapy may be recommended in vulnerable older patients with mCRC, rather than full-dose monotherapy.