Trifluridine/tipiracil plus bevacizumab as a first‐line treatment for elderly patients with metastatic colorectal cancer (KSCC1602): A multicenter phase II trial

• Published in: Cancer medicine (Malden, MA) MA), 2021-01, Vol.10 (2), p.454-461
• Main Authors: Oki, Eiji, Makiyama, Akitaka, Miyamoto, Yuji, Kotaka, Masahiko, Kawanaka, Hirofumi, Miwa, Keisuke, Kabashima, Akira, Noguchi, Tomohiro, Yuge, Kotaro, Kashiwada, Tomomi, Ando, Koji, Shimokawa, Mototsugu, Saeki, Hiroshi, Akagi, Yoshito, Baba, Hideo, Maehara, Yoshihiko, Mori, Masaki
• Format: Article
• Language: English
• Subjects: 5-Fluorouracil; Adverse events; Anorexia; Antiviral drugs; Bevacizumab; Cancer; Cancer therapies; Chemotherapy; Clinical Cancer Research; Clinical trials; Colorectal cancer; Colorectal carcinoma; Cytotoxicity; Disease control; Drug dosages; elderly; Frontotemporal dementia; Geriatrics; Hematology; Hypotheses; Immunotherapy; Irinotecan; Leukopenia; Metastases; Metastasis; Monoclonal antibodies; Neutropenia; Original Research; Oxaliplatin; Patients; Response rates; Survival; Targeted cancer therapy; thymidine phosphorylase inhibitor; Trifluridine
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.3618

Background A previous Phase I/II study demonstrated that TAS‐102 (trifluridine/tipiracil [FTD/TPI]) plus bevacizumab (Bev) has encouraging efficacy and controllable safety for patients with previously treated metastatic colorectal cancer. Therefore, we designed for assessing the efficacy and safety of FTD/TPI plus Bev in elderly patients with previously untreated metastatic colorectal cancer. Methods This is a multicenter, single‐arm Phase II study included patients ≥70 years old with previously untreated, unresectable metastatic colorectal cancer. Treatment consisted of FTD/TPI plus Bev given every 4 weeks. The primary endpoint was progression‐free survival (PFS), assuming a null hypothesis of a PFS of 5 months. The secondary endpoints were the overall survival (OS), overall response rate (ORR), and adverse events (AEs). Results Between 5 January 2017 and 13 March 2018, 39 patients were enrolled from 18 institutions. The median patient age was 76.0 years (range, 70–88); the ECOG‐PS was 0 in 24 patients and 1 in 15 patients. The median PFS was 9.4 months as a primary endpoint, and the median OS was 22.4 months. The ORR was 40.5% and the disease control rate was 86.5%. Grade 3–4 AEs included neutropenia (71.8%), leukopenia (51.3%), anorexia (15.4%), febrile neutropenia (10.3%), and fatigue (10.3%). Conclusions FTD/TPI plus Bev is an effective and well‐tolerated regimen for elderly patients with previously untreated metastatic colorectal cancer. Capecitabine/bevacizumab can be selected as a subsequent maintenance therapy without irinotecan and oxaliplatin because FTD/TPI has no cross‐resistance with 5‐fluorouracil. Clinical trial registration: UMIN clinical trials registry (UMIN000025241). We aimed to assess the efficacy and safety of FTD/TPI plus Bev in elderly patients with previously untreated metastatic colorectal cancer. The median PFS was 9.4 months as a primary endpoint, the median OS was 22.4 month, ORR was 40.5% and AEs were manageable. The combination of FTD/TPI plus Bev is an effective and well‐tolerated regimen for elderly patients with previously untreated metastatic colorectal cancer.