Pooled safety analysis of two phase 3 studies investigating trifluridine/tipiracil plus bevacizumab in patients with metastatic colorectal cancer
BackgroundTrifluridine/tipiracil (FTD/TPI) is approved as monotherapy and in combination with bevacizumab for the treatment of patients with refractory metastatic colorectal cancer (mCRC). FTD/TPI plus bevacizumab showed good tolerability in the phase 3 SOLSTICE (first-line) and SUNLIGHT (later-line...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2024.1506075/full |
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| author | Julien Taieb Marwan Fakih Gabor Liposits Gerald W. Prager Eric Van Cutsem Fortunato Ciardiello Nadia Amellal Elizabeth Calleja Mei Liu Lucas Roby Josep Tabernero Thierry André |
| author_facet | Julien Taieb Marwan Fakih Gabor Liposits Gerald W. Prager Eric Van Cutsem Fortunato Ciardiello Nadia Amellal Elizabeth Calleja Mei Liu Lucas Roby Josep Tabernero Thierry André |
| author_sort | Julien Taieb |
| collection | DOAJ |
| description | BackgroundTrifluridine/tipiracil (FTD/TPI) is approved as monotherapy and in combination with bevacizumab for the treatment of patients with refractory metastatic colorectal cancer (mCRC). FTD/TPI plus bevacizumab showed good tolerability in the phase 3 SOLSTICE (first-line) and SUNLIGHT (later-line) trials. This pooled analysis was performed to further characterize the safety of FTD/TPI plus bevacizumab and to compare safety in untreated and previously treated patients with mCRC.MethodsPatients must have received at least one dose of FTD/TPI plus bevacizumab in SOLSTICE (NCT03869892) or SUNLIGHT (NCT04737187). Treatment-emergent adverse events (TEAEs) in SOLSTICE and SUNLIGHT were graded per Common Terminology Criteria for Adverse Events versions 4.03 and 5.0, respectively. Times to onset/resolution of grade ≥3 hematologic TEAEs were assessed using Kaplan–Meier methodology. Treatment-related adverse events (TRAEs) were analyzed by age and Eastern Cooperative Oncology Group performance status (ECOG PS).ResultsThe pooled safety population comprised 669 patients (SOLSTICE, n = 423; and SUNLIGHT, n = 246). Grade ≥3 TEAEs were reported more frequently in SOLSTICE than in SUNLIGHT (86.8% vs. 72.4%), the most common being neutropenia and anemia. Overall, granulocyte colony-stimulating factor was used in 30.6% of patients. Median time to resolution of grade ≥3 hematologic adverse events/neutropenia to grade ≤2 was 8 days. Grade ≥3 TRAEs were more frequent in patients aged ≥75 years and those with an ECOG PS of 0 versus 1 or 2.ConclusionsFTD/TPI plus bevacizumab showed a consistent and manageable safety profile across first- and later-line mCRC treatment, including in vulnerable patients. Hematologic TEAEs were mostly reversible with appropriate management. |
| format | Article |
| id | doaj-art-edad01dcc65f43e099c7ec05b5c0e284 |
| institution | Kabale University |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Oncology |
| spelling | doaj-art-edad01dcc65f43e099c7ec05b5c0e2842025-01-16T05:10:18ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-01-011410.3389/fonc.2024.15060751506075Pooled safety analysis of two phase 3 studies investigating trifluridine/tipiracil plus bevacizumab in patients with metastatic colorectal cancerJulien Taieb0Marwan Fakih1Gabor Liposits2Gerald W. Prager3Eric Van Cutsem4Fortunato Ciardiello5Nadia Amellal6Elizabeth Calleja7Mei Liu8Lucas Roby9Josep Tabernero10Thierry André11Hôpital Européen Georges-Pompidou, University Paris-Cité (Paris Descartes), SIRC CARPEM, Paris, FranceDepartment of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA, United StatesDepartment of Oncology, Gødstrup Hospital, Herning, DenmarkDepartment of Medicine I, Medical University Vienna, Vienna, AustriaDigestive Oncology, University Hospitals Gasthuisberg Leuven and University of Leuven, Leuven, BelgiumDepartment of Precision Medicine, University of Campania Liuigi Vanvitelli, Naples, ItalyServier International Research Institute, Suresnes, FranceTaiho Oncology, Inc., Princeton, NJ, United StatesTaiho Oncology, Inc., Princeton, NJ, United StatesServier International Research Institute, Suresnes, FranceVall d’Hebron Hospital Campus, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain0Sorbonne University and Saint-Antoine Hospital, APHP, Paris, FranceBackgroundTrifluridine/tipiracil (FTD/TPI) is approved as monotherapy and in combination with bevacizumab for the treatment of patients with refractory metastatic colorectal cancer (mCRC). FTD/TPI plus bevacizumab showed good tolerability in the phase 3 SOLSTICE (first-line) and SUNLIGHT (later-line) trials. This pooled analysis was performed to further characterize the safety of FTD/TPI plus bevacizumab and to compare safety in untreated and previously treated patients with mCRC.MethodsPatients must have received at least one dose of FTD/TPI plus bevacizumab in SOLSTICE (NCT03869892) or SUNLIGHT (NCT04737187). Treatment-emergent adverse events (TEAEs) in SOLSTICE and SUNLIGHT were graded per Common Terminology Criteria for Adverse Events versions 4.03 and 5.0, respectively. Times to onset/resolution of grade ≥3 hematologic TEAEs were assessed using Kaplan–Meier methodology. Treatment-related adverse events (TRAEs) were analyzed by age and Eastern Cooperative Oncology Group performance status (ECOG PS).ResultsThe pooled safety population comprised 669 patients (SOLSTICE, n = 423; and SUNLIGHT, n = 246). Grade ≥3 TEAEs were reported more frequently in SOLSTICE than in SUNLIGHT (86.8% vs. 72.4%), the most common being neutropenia and anemia. Overall, granulocyte colony-stimulating factor was used in 30.6% of patients. Median time to resolution of grade ≥3 hematologic adverse events/neutropenia to grade ≤2 was 8 days. Grade ≥3 TRAEs were more frequent in patients aged ≥75 years and those with an ECOG PS of 0 versus 1 or 2.ConclusionsFTD/TPI plus bevacizumab showed a consistent and manageable safety profile across first- and later-line mCRC treatment, including in vulnerable patients. Hematologic TEAEs were mostly reversible with appropriate management.https://www.frontiersin.org/articles/10.3389/fonc.2024.1506075/fullclinical trialfirst-lineSOLSTICESUNLIGHTthird-line |
| spellingShingle | Julien Taieb Marwan Fakih Gabor Liposits Gerald W. Prager Eric Van Cutsem Fortunato Ciardiello Nadia Amellal Elizabeth Calleja Mei Liu Lucas Roby Josep Tabernero Thierry André Pooled safety analysis of two phase 3 studies investigating trifluridine/tipiracil plus bevacizumab in patients with metastatic colorectal cancer Frontiers in Oncology clinical trial first-line SOLSTICE SUNLIGHT third-line |
| title | Pooled safety analysis of two phase 3 studies investigating trifluridine/tipiracil plus bevacizumab in patients with metastatic colorectal cancer |
| title_full | Pooled safety analysis of two phase 3 studies investigating trifluridine/tipiracil plus bevacizumab in patients with metastatic colorectal cancer |
| title_fullStr | Pooled safety analysis of two phase 3 studies investigating trifluridine/tipiracil plus bevacizumab in patients with metastatic colorectal cancer |
| title_full_unstemmed | Pooled safety analysis of two phase 3 studies investigating trifluridine/tipiracil plus bevacizumab in patients with metastatic colorectal cancer |
| title_short | Pooled safety analysis of two phase 3 studies investigating trifluridine/tipiracil plus bevacizumab in patients with metastatic colorectal cancer |
| title_sort | pooled safety analysis of two phase 3 studies investigating trifluridine tipiracil plus bevacizumab in patients with metastatic colorectal cancer |
| topic | clinical trial first-line SOLSTICE SUNLIGHT third-line |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2024.1506075/full |
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