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

Abstract

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).

Appropriateness of Trifluridine/Tipiracil in the Clinical Practice of Third-Line Therapy in Metastatic Colorectal Cancer

“…In the Asian Phase III study, patients aged ≥65 years even seem to obtain a greater benefit than those <65 years [24]. A recent Phase II study in untreated patients aged ≥70 years demonstrated the safety of FTD/TPI in combination with bevacizumab (Bev) both in fit and vulnerable subjects, despite increased toxicity induced by Bev [25].…”

A Comparison of Bevacizumab Plus TAS-102 and TAS-102 Monotherapy for Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis

“…Recent data from the KSCC1602 study showed that bevacizumab combined with TAS-102 was an effective and well-tolerated regimen for elderly patients with untreated mCRC over 70 years of age. The median PFS was 9.4 months, the median OS was 22.4 months, and the ORR was 40.5% ( 36 ). This means that this treatment plan is expected to become one of the standard treatment options for metastatic colorectal cancer.…”

Nutritional Support Indications in Gastroesophageal Cancer Patients: From Perioperative to Palliative Systemic Therapy. A Comprehensive Review of the Last Decade

“…In the setting of advanced unresectable or metastatic GC, chemotherapy should be offered to patients with adequate performance status and organ function, as it improves QoL and survival outcomes over the best supportive care (BSC) alone [ 88 , 89 ]. Moreover, combination chemotherapy yields a survival advantage compared to single-agent regimens and is to be preferred over monotherapy in patients fit for combinatorial approaches [ 90 ].…”