Pre-planned safety analysis of NORDIC 9: A randomized trial comparing full dose monotherapy (S-1) with reduced dose combination therapy (S-1/oxaliplatin) in older chemo-naive patients with metastatic colorectal cancer (mCRC).

Abstract

10032 Background: More than half of the patients (pts) diagnosed with mCRC are older, but they are underrepresented in clinical trials. Data about the best treatment strategy in pts who are not candidates for standard full-dose combination therapy is scanty. Here we present a preplanned safety analysis in the NORDIC 9 trial. Methods: NORDIC 9 explores treatment of older mCRC pts (≥70 years) who are not candidates for full-dose combination therapy. Pts receive full dose monotherapy (Arm A: S-1 30 mg/m2 po bid day 1-14 q3w, followed by irinotecan upon progression or reduced dose (80%) combination therapy (Arm B: S-1 20 mg/m2 po bid day 1-14 + oxaliplatin 100 mg/m2 iv day 1 q3w, followed by reduced dose S-1 + irinotecan q3w). Bevacizumab (7.5 mg/kg iv day 1) may be added at the discretion of the treating clinician. Geriatric screening tools (eg G-8 and VES-13) and quality-of-life are evaluated at baseline. Blood samples and tumor tissue are prospectively collected. Primary endpoint is PFS. Secondary endpoints are correlations between the geriatric screening and safety but also efficacy. Results: The safety analysis was performed when 50 pts had received 3 cycles. 12 pts received bevacizumab. Median age was 79 (range 70-88) years, 26 pts were male, performance status was 0 (43%), 1 (38%) or 2 (19%). Five (10%) pts discontinued therapy after only 1 cycle due to toxicity (n = 2) or PD/clinical deterioration (n = 3); 45 pts (90%) continued therapy beyond 3 cycles. Pts receiving only 1 cycle had numerically a worse G-8 and VES-13 score. Grade 3-4 non-hematological toxicity was fatigue (6%), diarrhea (10%), nausea (4%) and vomiting (6%), and was experienced by 10 pts, 6 of them received ≥3 cycles of treatment. There was no hand-foot-syndrome, cardiac or hematological grade 3-4 toxicity. Dose intensity for S-1 was 0.98 (0.7-1.0) (arm A) and 0.93 (0.6-1.0) (Arm B), respectively, and for oxaliplatin 0.99 (0.4-1.0). Conclusions: The safety committee recommends to continue the trial without dose adjustments according to the original design. February 2017, 118 of planned 150 pts had been included. Clinical trial information: EudraCT no 2014-000394-39.