Capecitabine (Cap) and oxaliplatin (Ox) in elderly and/or frail patients with metastatic colorectal cancer: The FOCUS2 trial

Abstract

9030 Background: Elderly/frail patients, though commonly treated, are under-represented in clinical trials. Evidence is needed to guide choices of drugs and doses in this population. Methods: FOCUS2 is a multicenter, 2x2 factorial randomized trial for patients with unpretreated metastatic colorectal cancer judged unfit for full-dose combination chemotherapy. After comprehensive health assessment (CHA), randomization was to: (A) simplified LV5FU2 infusional fluorouracil/leucovorin (FU); (B) OxFU; (C) Cap; or (D) OxCap. In each case, starting doses were 80% standard, with an option to escalate to full-dose at 6 weeks (wk). The factorial questions were: (A+B v C+D) - does replacing FU with Cap improve quality of life (QL)? (primary endpoint: improved global QL at 12 wk [QLQ-C30]); and (A+C v B+D) - how much does Ox improve efficacy in this population? (primary endpoint: progression-free survival (PFS). Results: 460 patients were randomized, 22% < 70 yrs; 35% 70–75 yrs; 43% > 75 yrs. 22% were performance status (PS) 0; 49% PS1; 29% PS2. Primary comparisons: (see table ): global QL did not favor Cap over FU. Comparison of PFS favored the addition of oxaliplatin but did not reach significance (HR 0.87, 95% CI 0.71–1.06, p=0.16). Secondary comparisons: Compared with FU, Cap did not affect RR, PFS or 60-day mortality, but it increased the risk of gr =3 toxicity. Oxaliplatin significantly improved RECIST response (RR) by wk 12, did not increase gr =3 toxicity or 60-day mortality, but reduced the chance of improved QL at 12 wk. Conclusion: In this frail elderly population, substituting Cap for FU did not improve overall QL or efficacy, and significantly increased toxicity. Addition of Ox gave significantly higher anticancer activity without increasing toxicity, but at the cost of some reduction in QL at 12 wk. Planned analyses include correlating baseline CHA with treatment outcome. [Table: see text] [Table: see text]