Osteosarcoma with cell-cycle and fibroblast growth factor genomic alterations: case report of Molecular Tumor Board combination strategy resulting in long-term exceptional response
Abstract There is a paucity of information about molecularly driven therapy in osteosarcomas. We report a 31-year-old woman with chemotherapy–refractory metastatic osteosarcoma who was successfully treated with the combination of palbociclib (CDK4/6 inhibitor) and lenvatinib (multikinase FGFR inhibi...
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| Format: | Article |
| Language: | English |
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BMC
2022-08-01
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| Series: | Journal of Hematology & Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13045-022-01344-x |
| _version_ | 1811281909777432576 |
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| author | Hanna E. Persha Shumei Kato Pradip De Jacob J. Adashek Jason K. Sicklick Vivek Subbiah Razelle Kurzrock |
| author_facet | Hanna E. Persha Shumei Kato Pradip De Jacob J. Adashek Jason K. Sicklick Vivek Subbiah Razelle Kurzrock |
| author_sort | Hanna E. Persha |
| collection | DOAJ |
| description | Abstract There is a paucity of information about molecularly driven therapy in osteosarcomas. We report a 31-year-old woman with chemotherapy–refractory metastatic osteosarcoma who was successfully treated with the combination of palbociclib (CDK4/6 inhibitor) and lenvatinib (multikinase FGFR inhibitor), selected based on next generation sequencing that showed CDK4 and CCND2 amplifications (upregulates CDK4/6), and FGF6 (ligand for FGFR1,2 and 4), FGF23 (ligand for FGFR1,2,3, and 4) and FRS2 (adaptor protein for FGFR signaling) amplifications. The patient’s tumor showed 68% reduction in positron emission tomography (PET) avidity, lasting 31 months after therapy initiation, when a solitary recurrence occurred, was resected, and treatment continued. The patient remains on matched targeted therapy at 51 + months from the start of the combination. Treatment was given at reduced dosing (lenvatinib 10 mg oral daily (approved dose = 24 mg daily)) and palbociclib 75 mg oral daily, one week on and one week off (approved dose = 125 mg oral daily, three weeks on/one week off) and is tolerated well. Therefore, co-targeting the aberrant cyclin and FGFR pathways resulted in long-term exceptional response in a patient with refractory advanced osteosarcoma. |
| first_indexed | 2024-04-13T01:43:19Z |
| format | Article |
| id | doaj.art-9569186ceeb542d5af064c6816ae1426 |
| institution | Directory Open Access Journal |
| issn | 1756-8722 |
| language | English |
| last_indexed | 2024-04-13T01:43:19Z |
| publishDate | 2022-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Hematology & Oncology |
| spelling | doaj.art-9569186ceeb542d5af064c6816ae14262022-12-22T03:08:08ZengBMCJournal of Hematology & Oncology1756-87222022-08-011511510.1186/s13045-022-01344-xOsteosarcoma with cell-cycle and fibroblast growth factor genomic alterations: case report of Molecular Tumor Board combination strategy resulting in long-term exceptional responseHanna E. Persha0Shumei Kato1Pradip De2Jacob J. Adashek3Jason K. Sicklick4Vivek Subbiah5Razelle Kurzrock6College of Pharmacy, Purdue UniversityCenter for Personalized Cancer Therapy and Division of Hematology and Oncology, Department of Medicine, UC San Diego Moores Cancer CenterAvera Cancer InstituteDepartment of Oncology, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins HospitalDivision of Surgical Oncology, Department of Surgery, Center for Personalized Cancer Therapy, University of California San DiegoDivision of Cancer Medicine, Department of Investigational Cancer Therapeutics (Phase 1 Clinical Trials Program), University of Texas MD Anderson Cancer CenterGenomic Sciences and Precision Medicine Center, Medical College of WisconsinAbstract There is a paucity of information about molecularly driven therapy in osteosarcomas. We report a 31-year-old woman with chemotherapy–refractory metastatic osteosarcoma who was successfully treated with the combination of palbociclib (CDK4/6 inhibitor) and lenvatinib (multikinase FGFR inhibitor), selected based on next generation sequencing that showed CDK4 and CCND2 amplifications (upregulates CDK4/6), and FGF6 (ligand for FGFR1,2 and 4), FGF23 (ligand for FGFR1,2,3, and 4) and FRS2 (adaptor protein for FGFR signaling) amplifications. The patient’s tumor showed 68% reduction in positron emission tomography (PET) avidity, lasting 31 months after therapy initiation, when a solitary recurrence occurred, was resected, and treatment continued. The patient remains on matched targeted therapy at 51 + months from the start of the combination. Treatment was given at reduced dosing (lenvatinib 10 mg oral daily (approved dose = 24 mg daily)) and palbociclib 75 mg oral daily, one week on and one week off (approved dose = 125 mg oral daily, three weeks on/one week off) and is tolerated well. Therefore, co-targeting the aberrant cyclin and FGFR pathways resulted in long-term exceptional response in a patient with refractory advanced osteosarcoma.https://doi.org/10.1186/s13045-022-01344-xOsteosarcomaTargeted therapyPrecisionGenomic |
| spellingShingle | Hanna E. Persha Shumei Kato Pradip De Jacob J. Adashek Jason K. Sicklick Vivek Subbiah Razelle Kurzrock Osteosarcoma with cell-cycle and fibroblast growth factor genomic alterations: case report of Molecular Tumor Board combination strategy resulting in long-term exceptional response Journal of Hematology & Oncology Osteosarcoma Targeted therapy Precision Genomic |
| title | Osteosarcoma with cell-cycle and fibroblast growth factor genomic alterations: case report of Molecular Tumor Board combination strategy resulting in long-term exceptional response |
| title_full | Osteosarcoma with cell-cycle and fibroblast growth factor genomic alterations: case report of Molecular Tumor Board combination strategy resulting in long-term exceptional response |
| title_fullStr | Osteosarcoma with cell-cycle and fibroblast growth factor genomic alterations: case report of Molecular Tumor Board combination strategy resulting in long-term exceptional response |
| title_full_unstemmed | Osteosarcoma with cell-cycle and fibroblast growth factor genomic alterations: case report of Molecular Tumor Board combination strategy resulting in long-term exceptional response |
| title_short | Osteosarcoma with cell-cycle and fibroblast growth factor genomic alterations: case report of Molecular Tumor Board combination strategy resulting in long-term exceptional response |
| title_sort | osteosarcoma with cell cycle and fibroblast growth factor genomic alterations case report of molecular tumor board combination strategy resulting in long term exceptional response |
| topic | Osteosarcoma Targeted therapy Precision Genomic |
| url | https://doi.org/10.1186/s13045-022-01344-x |
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