Sequential compared to upfront treatment of metastatic colorectal cancer using oxaliplatin (Eloxatin) therapy may lead to similar outcomes

1. Sequential and upfront treatment of metastatic colorectal cancer (mCRC) with oxaliplatin (OX)-based therapy does not lead to significantly different overall survival.

Evidence Rating Level: 1 (Excellent)

While the incidence of mCRC rises sharply with age, clinical trials predominantly exclude patients over 65 years. Recent studies have shown triple therapy with fluoropyrimidine (FP), bevacizumab (BEV), and dose-adjusted chemotherapy to be a viable option for older patients. However, it is unclear if these patients should receive chemotherapy upfront or as an escalation strategy. This open-label, randomized, multicenter phase III trial included 311 patients who were randomized to receive FP (either capecitabine or 5-fluorouracil) and BEV followed by escalation to OX (sequential arm; n = 151; 79 patients < 70 years, 72 patients ≥ 70 years; 45.0% female) or FP (either capecitabine or 5-fluorouracil), BEV, and OX upfront (upfront arm; n 149; 72 patients < 70 years, 77 patients ≥ 70 years; 38.9% female). Patients in the sequential arm had OX added within one month of radiologic progression. There was no significant difference in median overall survival between the sequential treatment and upfront treatment arms (27.2 months vs. 27.4 months; hazard ratio, 1.00; 95% confidence interval, 0.76–1.33; p = 0.98). Patients ≥ 70 years had shorter overall survival compared with patients < 70 years (sequential arm: HR 1.44, 95% CI, 0.96–2.16; upfront arm: HR 1.77, 95% CI, 1.17–2.66). There was no significant interaction between age and overall survival (interaction p = 0.45). Quality of life was assessed with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30, which showed significantly smaller declines in physical functioning in the sequential treatment arm at 6 months (mean difference from baseline [SD], -1.02 [14.13] vs. -8.48 [18.32]; p = 0.0241) and 12 months (mean difference from baseline [SD], -2.92 [19.4] vs. -11.52 [15.39]; p = 0.0393), although this difference was no longer significant at 18 months. Overall, sequential and upfront treatment seem to yield similar survival outcomes, with sequential treatment possibly associated with a lower early treatment burden.

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