Trifluridine-tipiracil in previously treated patients with oestrogen receptor-positive, HER2-negative metastatic breast cancer (BOOG 2019-01 TIBET trial): a single-arm, multicentre, phase 2 trialResearch in context
Summary: Background: Effective later-line chemotherapy treatment options are scarce for patients with metastatic breast cancer (MBC). Trifluridine-tipiracil has shown survival benefit in heavily pre-treated patients with metastatic colorectal and in gastric cancer refractory to a fluoropyrimidine....
Saved in:
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-02-01
|
| Series: | EClinicalMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589537024006448 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832583830689546240 |
|---|---|
| author | Niels A.D. Guchelaar Ron H.J. Mathijssen Maaike de Boer Marlies L. van Bekkum Joan B. Heijns Birgit E.P.J. Vriens Mandy M. van Rosmalen Lonneke W. Kessels Lisanne Hamming Karin J. Beelen Peter Nieboer Susan M. van den Berg Esther Oomen-de Hoop Rhodé M. Bijlsma Monique E.M.M. Bos |
| author_facet | Niels A.D. Guchelaar Ron H.J. Mathijssen Maaike de Boer Marlies L. van Bekkum Joan B. Heijns Birgit E.P.J. Vriens Mandy M. van Rosmalen Lonneke W. Kessels Lisanne Hamming Karin J. Beelen Peter Nieboer Susan M. van den Berg Esther Oomen-de Hoop Rhodé M. Bijlsma Monique E.M.M. Bos |
| author_sort | Niels A.D. Guchelaar |
| collection | DOAJ |
| description | Summary: Background: Effective later-line chemotherapy treatment options are scarce for patients with metastatic breast cancer (MBC). Trifluridine-tipiracil has shown survival benefit in heavily pre-treated patients with metastatic colorectal and in gastric cancer refractory to a fluoropyrimidine. This study aimed to investigate the efficacy of trifluridine-tipiracil in a Western population of previously treated patients with oestrogen receptor (ER+), HER2− MBC to facilitate further optimization of this treatment strategy. Methods: Adult patients at least 18 years old diagnosed with hormone receptor positive, HER2− receptor negative MBC with a performance status of 0 or 1 who have been treated with capecitabine in the metastatic setting and up to two other lines of chemotherapy, including a taxane, were enrolled in this single-arm, multicentre, phase 2 study in the Netherlands. The participants received trifluridine-tipiracil 35 mg/m2 orally twice a day on days 1–5 and days 8–12 during a 28-day cycle until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint was the disease control rate (DCR) at 8 weeks, defined as the percentage of patients that had stable disease, partial response or complete response according to RECIST 1.1, in all patients that received at least one dose of trifluridine-tipiracil and met the key eligibility criteria defined a priori. Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, and quality of life and were performed in all patients that received at least one dose of trifluridine-tipiracil. The primary endpoint was considered met, justifying further research of this treatment regimen, if the lower boundary of the 80% confidence interval (CI) exceeded 30%. The study was registered within ClinicalTrials.gov (NCT04489173) and is closed for inclusion. Findings: Fifty female patients were enrolled from September 2020 to July 2023, with a median of 3 (IQR, 2–3) previous endocrine therapy lines and 2 (IQR, 2–3) chemotherapy lines for MBC. The DCR rate at 8 weeks was 64.0% (n = 32, 95% CI: 50.1–75.9%; 80% CI: 55.0–72.1%), thereby meeting the primary endpoint of this study. At data cutoff (January 8, 2024), the median follow-up time was 18.2 months (IQR, 13.1–25.1 months). The median PFS was 5.4 months (95% CI: 2.0–7.2 months) and the median OS 14.0 months (95% CI: 8.8–17.8 months). The safety profile of trifluridine-tipiracil aligned with expected toxicities and included leukopenia (n = 36, 69%), neutropenia (n = 43, 83%), and fatigue (n = 43, 83%). The most common grade 3–4 AEs were primarily haematological disorders and included neutropenia (n = 38, 73%), leukopenia (n = 15, 29%) and anaemia (n = 6, 12%). The most common SAEs (any grade) with a possible relationship with trifluridine-tipiracil included anaemia (n = 2) and vomiting (n = 2). No treatment-related deaths occurred. Quality of life scores remained stable throughout the treatment. Interpretation: Trifluridine-tipiracil demonstrated promising efficacy in heavily pre-treated patients with MBC, despite prior exposure to a fluoropyrimidine. Clinically, this suggests that trifluridine-tipiracil holds potential as a viable oral later-line treatment option with a manageable toxicity profile while maintaining quality of life. Preparations for a phase 3 trial are underway. Funding: Servier, France. |
| format | Article |
| id | doaj-art-044a906431db4bab88e3a48ed0540266 |
| institution | Kabale University |
| issn | 2589-5370 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EClinicalMedicine |
| spelling | doaj-art-044a906431db4bab88e3a48ed05402662025-01-28T04:14:49ZengElsevierEClinicalMedicine2589-53702025-02-0180103065Trifluridine-tipiracil in previously treated patients with oestrogen receptor-positive, HER2-negative metastatic breast cancer (BOOG 2019-01 TIBET trial): a single-arm, multicentre, phase 2 trialResearch in contextNiels A.D. Guchelaar0Ron H.J. Mathijssen1Maaike de Boer2Marlies L. van Bekkum3Joan B. Heijns4Birgit E.P.J. Vriens5Mandy M. van Rosmalen6Lonneke W. Kessels7Lisanne Hamming8Karin J. Beelen9Peter Nieboer10Susan M. van den Berg11Esther Oomen-de Hoop12Rhodé M. Bijlsma13Monique E.M.M. Bos14Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the NetherlandsDepartment of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the NetherlandsDepartment of Internal Medicine, Division of Medical Oncology, GROW-School for Oncology and Developmental Biology, Maastricht UMC+, Maastricht, the NetherlandsDepartment of Internal Medicine, Reinier de Graaf Hospital, Delft, the NetherlandsDepartment of Internal Medicine, Amphia, Breda, the NetherlandsDepartment of Internal Medicine, Catharina Hospital, Eindhoven, the NetherlandsDepartment of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the NetherlandsDepartment of Internal Medicine, Deventer Hospital, Deventer, the NetherlandsDepartment of Internal Medicine, Medical Center Leeuwarden, Leeuwarden, the NetherlandsDepartment of Internal Medicine, Rijnstate, Arnhem, the NetherlandsDepartment of Internal Medicine, Wilhelmina Hospital Assen, Assen, the NetherlandsDutch Breast Cancer Research Group (BOOG), the NetherlandsDepartment of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the NetherlandsDepartment of Medical Oncology, UMC Utrecht Cancer Center, Utrecht, the NetherlandsDepartment of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands; Corresponding author. Department of Medical Oncology, Erasmus MC Cancer Institute, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands.Summary: Background: Effective later-line chemotherapy treatment options are scarce for patients with metastatic breast cancer (MBC). Trifluridine-tipiracil has shown survival benefit in heavily pre-treated patients with metastatic colorectal and in gastric cancer refractory to a fluoropyrimidine. This study aimed to investigate the efficacy of trifluridine-tipiracil in a Western population of previously treated patients with oestrogen receptor (ER+), HER2− MBC to facilitate further optimization of this treatment strategy. Methods: Adult patients at least 18 years old diagnosed with hormone receptor positive, HER2− receptor negative MBC with a performance status of 0 or 1 who have been treated with capecitabine in the metastatic setting and up to two other lines of chemotherapy, including a taxane, were enrolled in this single-arm, multicentre, phase 2 study in the Netherlands. The participants received trifluridine-tipiracil 35 mg/m2 orally twice a day on days 1–5 and days 8–12 during a 28-day cycle until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint was the disease control rate (DCR) at 8 weeks, defined as the percentage of patients that had stable disease, partial response or complete response according to RECIST 1.1, in all patients that received at least one dose of trifluridine-tipiracil and met the key eligibility criteria defined a priori. Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, and quality of life and were performed in all patients that received at least one dose of trifluridine-tipiracil. The primary endpoint was considered met, justifying further research of this treatment regimen, if the lower boundary of the 80% confidence interval (CI) exceeded 30%. The study was registered within ClinicalTrials.gov (NCT04489173) and is closed for inclusion. Findings: Fifty female patients were enrolled from September 2020 to July 2023, with a median of 3 (IQR, 2–3) previous endocrine therapy lines and 2 (IQR, 2–3) chemotherapy lines for MBC. The DCR rate at 8 weeks was 64.0% (n = 32, 95% CI: 50.1–75.9%; 80% CI: 55.0–72.1%), thereby meeting the primary endpoint of this study. At data cutoff (January 8, 2024), the median follow-up time was 18.2 months (IQR, 13.1–25.1 months). The median PFS was 5.4 months (95% CI: 2.0–7.2 months) and the median OS 14.0 months (95% CI: 8.8–17.8 months). The safety profile of trifluridine-tipiracil aligned with expected toxicities and included leukopenia (n = 36, 69%), neutropenia (n = 43, 83%), and fatigue (n = 43, 83%). The most common grade 3–4 AEs were primarily haematological disorders and included neutropenia (n = 38, 73%), leukopenia (n = 15, 29%) and anaemia (n = 6, 12%). The most common SAEs (any grade) with a possible relationship with trifluridine-tipiracil included anaemia (n = 2) and vomiting (n = 2). No treatment-related deaths occurred. Quality of life scores remained stable throughout the treatment. Interpretation: Trifluridine-tipiracil demonstrated promising efficacy in heavily pre-treated patients with MBC, despite prior exposure to a fluoropyrimidine. Clinically, this suggests that trifluridine-tipiracil holds potential as a viable oral later-line treatment option with a manageable toxicity profile while maintaining quality of life. Preparations for a phase 3 trial are underway. Funding: Servier, France.http://www.sciencedirect.com/science/article/pii/S2589537024006448Trifluridine-tipiracilMetastatic breast cancerChemotherapyTreatment |
| spellingShingle | Niels A.D. Guchelaar Ron H.J. Mathijssen Maaike de Boer Marlies L. van Bekkum Joan B. Heijns Birgit E.P.J. Vriens Mandy M. van Rosmalen Lonneke W. Kessels Lisanne Hamming Karin J. Beelen Peter Nieboer Susan M. van den Berg Esther Oomen-de Hoop Rhodé M. Bijlsma Monique E.M.M. Bos Trifluridine-tipiracil in previously treated patients with oestrogen receptor-positive, HER2-negative metastatic breast cancer (BOOG 2019-01 TIBET trial): a single-arm, multicentre, phase 2 trialResearch in context EClinicalMedicine Trifluridine-tipiracil Metastatic breast cancer Chemotherapy Treatment |
| title | Trifluridine-tipiracil in previously treated patients with oestrogen receptor-positive, HER2-negative metastatic breast cancer (BOOG 2019-01 TIBET trial): a single-arm, multicentre, phase 2 trialResearch in context |
| title_full | Trifluridine-tipiracil in previously treated patients with oestrogen receptor-positive, HER2-negative metastatic breast cancer (BOOG 2019-01 TIBET trial): a single-arm, multicentre, phase 2 trialResearch in context |
| title_fullStr | Trifluridine-tipiracil in previously treated patients with oestrogen receptor-positive, HER2-negative metastatic breast cancer (BOOG 2019-01 TIBET trial): a single-arm, multicentre, phase 2 trialResearch in context |
| title_full_unstemmed | Trifluridine-tipiracil in previously treated patients with oestrogen receptor-positive, HER2-negative metastatic breast cancer (BOOG 2019-01 TIBET trial): a single-arm, multicentre, phase 2 trialResearch in context |
| title_short | Trifluridine-tipiracil in previously treated patients with oestrogen receptor-positive, HER2-negative metastatic breast cancer (BOOG 2019-01 TIBET trial): a single-arm, multicentre, phase 2 trialResearch in context |
| title_sort | trifluridine tipiracil in previously treated patients with oestrogen receptor positive her2 negative metastatic breast cancer boog 2019 01 tibet trial a single arm multicentre phase 2 trialresearch in context |
| topic | Trifluridine-tipiracil Metastatic breast cancer Chemotherapy Treatment |
| url | http://www.sciencedirect.com/science/article/pii/S2589537024006448 |
| work_keys_str_mv | AT nielsadguchelaar trifluridinetipiracilinpreviouslytreatedpatientswithoestrogenreceptorpositiveher2negativemetastaticbreastcancerboog201901tibettrialasinglearmmulticentrephase2trialresearchincontext AT ronhjmathijssen trifluridinetipiracilinpreviouslytreatedpatientswithoestrogenreceptorpositiveher2negativemetastaticbreastcancerboog201901tibettrialasinglearmmulticentrephase2trialresearchincontext AT maaikedeboer trifluridinetipiracilinpreviouslytreatedpatientswithoestrogenreceptorpositiveher2negativemetastaticbreastcancerboog201901tibettrialasinglearmmulticentrephase2trialresearchincontext AT marlieslvanbekkum trifluridinetipiracilinpreviouslytreatedpatientswithoestrogenreceptorpositiveher2negativemetastaticbreastcancerboog201901tibettrialasinglearmmulticentrephase2trialresearchincontext AT joanbheijns trifluridinetipiracilinpreviouslytreatedpatientswithoestrogenreceptorpositiveher2negativemetastaticbreastcancerboog201901tibettrialasinglearmmulticentrephase2trialresearchincontext AT birgitepjvriens trifluridinetipiracilinpreviouslytreatedpatientswithoestrogenreceptorpositiveher2negativemetastaticbreastcancerboog201901tibettrialasinglearmmulticentrephase2trialresearchincontext AT mandymvanrosmalen trifluridinetipiracilinpreviouslytreatedpatientswithoestrogenreceptorpositiveher2negativemetastaticbreastcancerboog201901tibettrialasinglearmmulticentrephase2trialresearchincontext AT lonnekewkessels trifluridinetipiracilinpreviouslytreatedpatientswithoestrogenreceptorpositiveher2negativemetastaticbreastcancerboog201901tibettrialasinglearmmulticentrephase2trialresearchincontext AT lisannehamming trifluridinetipiracilinpreviouslytreatedpatientswithoestrogenreceptorpositiveher2negativemetastaticbreastcancerboog201901tibettrialasinglearmmulticentrephase2trialresearchincontext AT karinjbeelen trifluridinetipiracilinpreviouslytreatedpatientswithoestrogenreceptorpositiveher2negativemetastaticbreastcancerboog201901tibettrialasinglearmmulticentrephase2trialresearchincontext AT peternieboer trifluridinetipiracilinpreviouslytreatedpatientswithoestrogenreceptorpositiveher2negativemetastaticbreastcancerboog201901tibettrialasinglearmmulticentrephase2trialresearchincontext AT susanmvandenberg trifluridinetipiracilinpreviouslytreatedpatientswithoestrogenreceptorpositiveher2negativemetastaticbreastcancerboog201901tibettrialasinglearmmulticentrephase2trialresearchincontext AT estheroomendehoop trifluridinetipiracilinpreviouslytreatedpatientswithoestrogenreceptorpositiveher2negativemetastaticbreastcancerboog201901tibettrialasinglearmmulticentrephase2trialresearchincontext AT rhodembijlsma trifluridinetipiracilinpreviouslytreatedpatientswithoestrogenreceptorpositiveher2negativemetastaticbreastcancerboog201901tibettrialasinglearmmulticentrephase2trialresearchincontext AT moniqueemmbos trifluridinetipiracilinpreviouslytreatedpatientswithoestrogenreceptorpositiveher2negativemetastaticbreastcancerboog201901tibettrialasinglearmmulticentrephase2trialresearchincontext |