620PBevacizumab plus trifluridine/tipiracil in elderly patients with previously untreated metastatic colorectal cancer (KSCC 1602): A single-arm, phase II study

Background Elderly patients often cannot tolerate the usual combination of two cytotoxic agents. Recently, bevacizumab plus trifluridine/tipiracil (FTD/TPI) was shown to be a good candidate regimen for vulnerable patients. We aimed to assess the efficacy and safety of bevacizumab plus FTD/TPI in elderly patients with metastatic colorectal cancer. Methods Patients aged 70 years or older, with previously untreated unresectable, metastatic colorectal cancer, who were not deemed to be candidates for oxaliplatin-based or irinotecan-based chemotherapy regimens, were included in this trial. The treatment consisted of FTD/TPI (35 mg/m2, twice daily on Days 1–5 and Days 8–12) with bevacizumab (5mg/kg intravenously on Day 1 and 15), administrated every 4 weeks until disease progression. The primary endpoint was progression-free survival (PFS). Based on a previous report, we estimated the expected PFS as 9 months and the lower limit of interest as 5 months. As this research was designed to have a statistical power of 80% and one-sided type I error of 0.10, we calculated that 32 patients were required and planned enrolling 35 patients. The secondary endpoints were response rate (ORR), overall survival (OS), and adverse events (AEs). Results Between 2017 January and 2018 March, 39 patients (17 male; 22 female), with a median age of 77.5 years (range: 70–88), ECOG performance status 0 (79.5%) or 1 (20.5%), and RAS WT/MT/Unknown 23.1/41.0/35.9% were enrolled. The median PFS was 8.0 months (80% CI 6.7–11.2), and the median OS was not reached. The best response was 40.5% (15/37; 95% CI: 24.8–57.9), and the disease control rate was 86.5% (32/37; 95% CI: 71.2–95.5). The most frequently occurring grade 3 or 4 AEs were neutropenia (71.8%), leucopenia (48.7%), hypertension (20.5%), anemia (17.9%), anorexia (12.8%), febrile neutropenia (10.3%), and fatigue (10.3%). No treatment-related deaths occurred. Conclusions In this Phase 2 KSCC 1602 trial of bevacizumab plus FTD/TPI, the primary endpoint of PFS was achieved. This combination therapy showed favorable survival outcomes with an acceptable safety profile for elderly patients with previously untreated metastatic colorectal cancer. Clinical trial identification UMI25241. Legal entity responsible for the study Kyushu Study group of Clinical Cancer. Funding Taho Pharmaceutical. Disclosure A. Makiyama: Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lily Pharmaceutical; Speaker Bureau / Expert testimony: Chugai Pharmaceutical; Speaker Bureau / Expert testimony: Taiho Pharmaceutical; Speaker Bureau / Expert testimony: Takeda Pharmaceutical. M. Kotaka: Honoraria (self): Yakult Honsya; Honoraria (self): Chugai pharmaceutical. H. Baba: Research grant / Funding (institution): Taiho pharmaceutical; Research grant / Funding (institution): Chugai pharmaceutical. M. Mori: Research grant / Funding (institution): Taiho Pharmaceutical Co, Ltd. All other authors have declared no conflicts of interest.