Dataset Information

TRIFLURIDINE/TIPIRACIL (FTD/TPI) with or without bevacizumab in previously treated patients with esophago-gastric adenocarcinoma, a randomised phase III trial.

ABSTRACT:

Background

Trifluridine-tipiracil has shown a survival benefit compared with placebo in patients with chemorefractory metastatic esophago-gastric adenocarcinoma. We aimed to compare the efficacy of trifluridine-tipiracil plus bevacizumab vs trifluridine-tipiracil monotherapy in pre-treated patients with metastatic esophago-gastric adenocarcinoma.

Methods

This investigator-initiated, open-label, randomized trial enrolled patients with metastatic esophago-gastric adenocarcinoma. The main inclusion criteria were patients with pre-treated metastatic esophago-gastric adenocarcinoma, and WHO performance status 0 or 1. Participants were randomly assigned (1:1) to receive oral trifluridine-tipiracil (35 mg/m² twice daily on days 1-5 and 8-12 every 28 days) alone or combined with bevacizumab (5 mg/kg on days 1 and 15) until progression, unacceptable toxicity, or patient decision to withdraw. Randomisation was stratified by sex and treatment line. The primary endpoint was investigator-evaluated progression-free survival. All analyses were based on intention to treat. This trial is registered with EudraCT, 2018-004845-18.

Findings

From Oct 1, 2019, to Sept 30, 2021, 103 patients were enrolled and randomly assigned to trifluridine-tipiracil (n = 53) or trifluridine-tipiracil plus bevacizumab (n = 50). The clinical cut-off date was March 1st, 2023, after a median follow-up of 36.6 months. Median progression-free survival was 3.1 months (95% CI 2.0-4.3) in the trifluridine-tipiracil group vs 3.9 months (3.0-6.3) in the trifluridine-tipiracil plus bevacizumab group (hazard ratio 0.68, 95% CI 0.46-1.02; p = 0.058). The most frequent grade 3 or worse adverse event was neutropenia, observed in 26 (49%) patients in the trifluridine-tipiracil group vs 23 patients (46%) in the trifluridine-tipiracil plus bevacizumab group. At least one hospitalization was observed in 21 patients (40%) in the trifluridine-tipiracil group and 22 patients (44%) in the trifluridine-tipiracil plus bevacizumab group. No deaths were deemed treatment related.

Interpretation

In patients with pre-treated metastatic esophago-gastric cancer, trifluridine-tipiracil plus bevacizumab, compared to trifluridine-tipiracil monotherapy, did not significantly prolong progression-free survival. The combination of trifluridine-tipiracil with bevacizumab was well tolerated without increase in severe neutropenia and no new safety signals.

Funding

Servier, Roche.

SUBMITTER: Baeksgaard Jensen L

PROVIDER: S-EPMC10940909 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature

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Publications

TRIFLURIDINE/TIPIRACIL (FTD/TPI) with or without bevacizumab in previously treated patients with esophago-gastric adenocarcinoma, a randomised phase III trial.

Baeksgaard Jensen Lene L Yilmaz Mette M Nordsmark Marianne M Möller Sören S Elle Ida Coordt IC Ladekarl Morten M Qvortrup Camilla C Pfeiffer Per P

EClinicalMedicine 20240308

<h4>Background</h4>Trifluridine-tipiracil has shown a survival benefit compared with placebo in patients with chemorefractory metastatic esophago-gastric adenocarcinoma. We aimed to compare the efficacy of trifluridine-tipiracil plus bevacizumab vs trifluridine-tipiracil monotherapy in pre-treated patients with metastatic esophago-gastric adenocarcinoma.<h4>Methods</h4>This investigator-initiated, open-label, randomized trial enrolled patients with metastatic esophago-gastric adenocarcinoma. The ...[more]

PMID: 38495525

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Project description:Background and study aims Worldwide, nearly 1.25 million patients are diagnosed with colorectal cancer each year. At least 50% of patients develop metastases, and most of these patients have unresectable tumours (unable to be removed). Standard treatment for these patients involves chemotherapy and monoclonal antibodies targeting vascular endothelial growth factor (VEGF the cells that stimulate formation of blood vessels). In patients with KRAS wild-type tumours (abnormal tumours), monoclonal antibodies targeting epidermal growth factor receptor (EGFR which stimulates cell growth) are also used. 5-year survival rates in patients with metastatic colorectal cancer (mCRC), representing Stage IV CRC, were reached by only about 15% of mCRC patients. Although the outcome of patients with mCRC has clearly improved during recent years with median survival now reaching more than 30 months in recent clinical trials, more treatment options are needed for patients with disease progression after fluoropyrimidine (e.g. 5-FU), irinotecan, oxaliplatin, applicable anti-VEGF agents and anti-EGFR agents or those unable to tolerate these agents. Trifluridine/tipiracil (FTD/TPI; Lonsurf®) has been authorized in the EU since April 2016 for treatment of these patients. On the basis of the severity of the tumour disease with rather limited treatment options within the context of a previously treated tumour disease in the end-of-life situation, the health-related quality of life (HRQoL) is very important to describe the impact of treatment on the patient’s functioning regarding physical health (including disease-related morbidity), social, emotional, cognitive and role aspects. Changes of HRQoL during and after treatment with FTD/TPI have not been investigated so far in clinical trials. The aim of this study is to investigate the HRQoL in patients treated with FTD/TPI and those who are treated with best-supportive-care (BSC) while being suitable for treatment with FTD/TPI according to the summary of product characteristics. Who can participate? Adults aged 18 and older who have colorectal cancer. What does the study involve? Participants who are eligible for FTD/TPI therapy are treated like mCRC cancer patients in regular medical service receiving FTD/TPI with the only exemption that these cancer patients have to fill out 2 questionnaires (in total 36 questions) concerning their quality of life at treatment baseline and at the end of each FTD/TPI treatment cycle until end-of-treatment (i.e. disease progression).

Dataset Information

TRIFLURIDINE/TIPIRACIL (FTD/TPI) with or without bevacizumab in previously treated patients with esophago-gastric adenocarcinoma, a randomised phase III trial.

Background

Methods

Findings

Interpretation

Funding

Publications

TRIFLURIDINE/TIPIRACIL (FTD/TPI) with or without bevacizumab in previously treated patients with esophago-gastric adenocarcinoma, a randomised phase III trial.

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