NORDIC9: A randomized phase II trial comparing first-line palliative full-dose monotherapy (S-1) with reduced dose-combination therapy (SOx) in older and frail patients with metastatic colorectal cancer (mCRC)

Background: Most patients (pts) with mCRC are older than 70 years, but they are underrepresented in clinical trials. NORDIC9 evaluated efficacy of palliative treatment strategies based on S-1, which has previously demonstrated less toxicity but similar efficacy as 5FU, and here we present initial results.Methods: Older mCRC pts (≥70 years) who were not candidates for full-dose combination therapy, were randomized to full-dose monotherapy (Arm A: S-1 30 mg/m2 po bid d 1-14 q3w, followed by irinotecan upon progression) or reduced (80\ combination therapy (Arm B: S-1 20 mg/m2 po bid d 1-14 + oxaliplatin 100 mg/m2 iv d 1 q3w, followed by S-1 + irinotecan q3w). Addition of bevacizumab (7.5 mg/kg iv d 1) before randomization was optional. Geriatric screening tools (G-8, VES-13, handgrip strength, Timed-Up-and-Go), Charlson Comorbidity Index and quality of life were evaluated at baseline. Blood samples and tumor tissue were prospectively collected. Primary endpoint was PFS. Secondary endpoints were response rate, survival and correlations between screening tools, efficacy and safety.