Bone Cancer Treatment Regimens
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Bone Cancer Treatment Regimens |
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Clinical Trials: The NCCN recommends cancer patient participation in clinical trials as the gold standard for treatment. |
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Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced health care team. Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly. The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are provided only to supplement the latest treatment strategies. These Guidelines are a work in progress that may be refined as often as new significant data become available. The NCCN Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way. |
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Note: All recommendations are Category 2A unless otherwise indicated. |
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▶Systemic Therapy for MSI-H/dMMR Tumors1 |
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REGIMEN |
DOSING |
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Preferred Regimens |
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Pembrolizumab2-6,a |
Day 1: Pembrolizumab 200mg IV over 30 minutes. Repeat cycle every 3 weeks for up to 2 years. OR Day 1: Pembrolizumab 400mg IV over 30 minutes. Repeat cycle every 6 weeks for up to 2 years. |
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▶Systemic Therapy for TMB-H (≥10 mutations/megabase) Tumors1 |
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Useful in Certain Circumstances |
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Pembrolizumab2-6,b |
Day 1: Pembrolizumab 200mg IV over 30 minutes. Repeat cycle every 3 weeks for up to 2 years. OR Day 1: Pembrolizumab 400mg IV over 30 minutes. Repeat cycle every 6 weeks for up to 2 years. |
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▶Systemic Therapy for Chondrosarcoma: Metastatic and Widespread Disease |
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Other Recommended Regimens |
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Dasatinib7-9,c |
Days 1-28: Dasatinib 70mg-100mg orally twice daily. Repeat cycle every 4 weeks. |
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Pazopanib10,11,c |
Days 1-28: Pazopanib 800mg orally daily. Repeat cycle every 4 weeks. |
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▶Systemic Therapy for Chondrosarcoma Conventional (Grades 1-3)1 |
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Preferred Regimens |
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No known standard chemotherapy options1 |
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Useful in Certain Circumstances |
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Ivosidenib (for susceptible IDH1 mutations)12,13,c |
Days 1-28: Ivosidenib 500mg orally daily. Repeat cycle every 4 weeks. |
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▶Systemic Therapy for Chondrosarcoma Dedifferentiated1 |
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Preferred Regimens |
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Follow osteosarcoma regimens (Category 2B)1 |
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Useful in Certain Circumstances |
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Ivosidenib (for susceptible IDH1 mutations)12-13,c |
Days 1-28: Ivosidenib 500mg orally daily. Repeat cycle every 4 weeks. |
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▶Systemic Therapy for Chondrosarcoma Mesenchymal1 |
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Preferred Regimens |
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Follow Ewing Sarcoma Regimens (Category 2B)1 |
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▶Systemic Therapy for Chordoma1 |
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Other Recommended Regimens |
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Dasatinib7-9,c |
Days 1-28: Dasatinib 70mg-100mg orally twice daily. Repeat cycle every 4 weeks. |
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Imatinib14,c |
Days 1-28 : Imatinib 400mg orally twice daily. Repeat cycle every 4 weeks. |
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Sunitinib17,18,c,e |
Days 1-28: Sunitinib 37.5mg orally daily. Repeat cycle every 4 weeks. |
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Useful in Certain Circumstances |
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Erlotinib19,20,c |
Days 1-28: Erlotinib 150mg orally once daily. Repeat cycle every 4 weeks. |
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Imatinib + Cisplatin14,19,21,22,c,d |
Day 1: Cisplatin 25mg/m2 IV over 60 minutes. Days 1-7: Imatinibc 400mg orally daily. Repeat cycle every week. |
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Imatinib + Sirolimus14,23,24,c |
Days 1-28: Imatinib 400mg orally once daily Days 1-28: Sirolimus 2mg orally once daily (dose is adjusted to keep concentration within therapeutic range of 15-20 ng/mL). Repeat cycle every 4 weeks. |
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Lapatinib (for EGFR mutation-positive chordomas)25,26,c |
Days 1-28: Lapatinib 1500mg orally once daily. Repeat cycle every 4 weeks. |
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Sorafenib27-30,c,e |
Days 1-28: Sorafenib 400mg orally twice daily. Repeat cycle every 4 weeks. |
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▶Ewing Sarcoma First-line Therapy (Primary/Neoadjuvant/Adjuvant Therapy)1 |
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Preferred Regimens |
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VDC/IE (Vincristine + Doxorubicin/Dactinomycin + Cyclophosphamide Alternate with Ifosfamide and Etoposide) (Category 1)31-36,f-i |
Day 1: Vincristine 2mg/m2 (maximum 2mg) IV over 5-10 minutes Day 1: Doxorubicin 75mg/m2 IV push OR Day 1: Dactinomycin 1,250mcg/m2 IV push Day 1: Cyclophosphamide 1,200mg/m2 IV over 60 minutes Day 1: Mesna 240mg/m2 IV over 15 minutes three times daily (one dose before cyclophosphamide, then at 4 and 8 hours from the start of each cyclophosphamide dose) Repeat cycle every 3 weeks for cycles 1 and 3 (neoadjuvant) and cycles 5, 7, 9, 11, 13, 15, and 17 (adjuvant), or cycles 1, 3, 5, 7, 9, 11, 13, 15, and 17 (metastatic), alternating with: Days 1-5: Ifosfamide 1,800mg/m2 IV over 3 hours daily Days 1-5: Mesna 360mg/m2 IV over 15 minutes three times daily (one dose before ifosfamide, then at 4 and 8 hours from the start of each ifosfamide dose) Days 1-5: Etoposide 100mg/m2 IV over 60 minutes daily. Repeat cycle every 3 weeks for cycles 2 and 4 (neoadjuvant) and cycles 6, 8, 10, 12, 14, and 16 (adjuvant) or cycles 2, 4, 6, 8, 10, 12, 14, and 16 (metastatic), alternating with: VDC regimen (shown above). |
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VDC/IE (as neoadjuvant/adjuvant therapy for patients aged <50 years) (Category 1)31-37,f-i |
Day 1: Vincristine 2mg/m2 IV (maximum 2mg) IV over 5-10 minutes Days 1-2: Doxorubicin 37.5mg/m2 IV over 5-10 minutes OR Day 1: Doxorubicin 75mg/m2 IV push OR Day 1: Dactinomycin 1,250mcg/m2 IV push Day 1: Cyclophosphamide 1,200mg/m2 IV over 60 minutes Day 1: Mesna 240mg/m2 IV over 15 minutes three times daily (one dose before cyclophosphamide, then at 4 and 8 hours from the start of each cyclophosphamide dose). Repeat cycle every 2 weeks for cycles 1, 3, and 5 (neoadjuvant) and cycles 7, 9, 11, and 13 (adjuvant), alternating with: Days 1-5: Ifosfamide 1,800mg/m2 IV over 3 hours daily Days 1-5: Mesna 360mg/m2 IV over 15 minutes three times daily (one dose before ifosfamide, then at 4 and 8 hours from the start of each ifosfamide dose). Days 1-5: Etoposide 100mg/m2 IV over 60 minutes daily. Repeat cycle every 2 weeks for cycles 2, 4, and 6 (neoadjuvant) and cycles 8, 10, 12, and 14 (adjuvant), alternating with: VDC regimen (shown above). |
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Other Recommended Regimens |
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VAI (Vincristine + Doxorubicin/Dactinomycin + Ifosfamide)31,32,34,38,39,f,g,i |
Day 1: Vincristine 1.5mg/m2 (maximum 2mg) IV over 5-10 minutes Days 1-2: Doxorubicin (even numbered cycles) 30mg/m2 IV push once daily Days 1-3: Dactinomycin (odd-numbered cycles) 500mcg/m2 IV push once daily Days 1-3: Ifosfamide 2,000mg/m2 IV over 3 hours once daily Days 1-3: Mesna 400mg/m2 IV over 15 minutes three times daily (once prior to ifosfamide, then at 4 and 8 hours from the start of each ifosfamide dose). Repeat cycle every 3 weeks for 4-8 cycles (neoadjuvant) and 5-12 cycles (adjuvant) or 14 cycles (metastatic). |
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VIDE (Vincristine + Ifosfamide + Doxorubicin/Dactinomycin + Etoposide)31,32,34,35,40,41,f,g,i |
Day 1: Vincristine 1.5mg/m2 (maximum 2mg) IV over 5-10 minutes Days 1-3: Ifosfamide 3,000mg/m2 IV over 3 hours daily Days 1-3: Mesna 600mg/m2 IV over 15 minutes 3 times daily (once prior to ifosfamide, then at 4 and 8 hours from the start of each ifosfamide dose) Days 1-3: Doxorubicin 20mg/m2 IV push daily OR Days 1-3: Dactinomycin 500mcg/m2 IV push daily Days 1-3: Etoposide 150mg/m2 IV over 60 minutes daily. Repeat cycle every 3 weeks for 4-8 cycles (neoadjuvant) and 5-12 cycles (adjuvant) for total of 9-16 cycles or 14 cycles total (metastatic). |
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▶Ewing Sarcoma Primary Therapy for Metastatic Disease at Initial Presentation1 |
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Preferred Regimens |
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VDC/IE (Vincristine + Doxorubicin/Dactinomycin + Cyclophosphamide Alternate with Ifosfamide and Etoposide)31-37,f,g,i |
Day 1: Vincristine 2mg/m2 (maximum 2mg) IV over 5-10 minutes Day 1: Doxorubicin 75mg/m2 IV push OR Day 1: Dactinomycin 1,250mcg/m2 IV push Day 1: Cyclophosphamide 1,200mg/m2 IV over 60 minutes Day 1: Mesna 240mg/m2 IV over 15 minutes three times daily (one dose before cyclophosphamide, then at 4 and 8 hours from the start of each cyclophosphamide dose) Repeat cycle every 3 weeks for cycles 1, 3, 5, 7, 9, 11, 13, 15, and 17 (metastatic), alternating with: Days 1-5: Ifosfamide 1,800mg/m2 IV over 3 hours daily Days 1-5: Mesna 360mg/m2 IV over 15 minutes three times daily (one dose before ifosfamide, then at 4 and 8 hours from the start of each ifosfamide dose) Days 1-5: Etoposide 100mg/m2 IV over 60 minutes daily. Repeat cycle every 3 weeks for cycles 2, 4, 6, 8, 10, 12, 14, and 16 (metastatic), alternating with: VDC regimen (shown above). |
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VAI (Vincristine + Doxorubicin/Dactinomycin + Ifosfamide)31,32,34,38,39,f,g,i |
Day 1: Vincristine 1.5mg/m2 (maximum 2mg) IV over 5-10 minutes Days 1-2: Doxorubicin (even numbered cycles) 30mg/m2 IV push once daily Days 1-3: Dactinomycin (odd-numbered cycles) 500mcg/m2 IV push once daily Days 1-3: Ifosfamide 2,000mg/m2 IV over 3 hours once daily Days 1-3: Mesna 400mg/m2 IV over 15 minutes three times daily (once prior to ifosfamide, then at 4 and 8 hours from the start of each ifosfamide dose). Repeat cycle every 3 weeks for 14 cycles. |
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VDC (Vincristine + Doxorubicin/Dactinomycin + Cyclophosphamide)31-33,42,f,i |
Day 1: Vincristine 2mg/m2 (maximum 2mg) IV over 5-10 minutes Day 1: Doxorubicin 75mg/m2 IV push OR Day 1: Dactinomycin 1,250mcg/m2 IV push Day 1: Cyclophosphamide 1,200mg/m2 IV over 60 minutes. Repeat cycle every 3 weeks for 17 cycles. |
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VIDE (Vincristine + Ifosfamide + Doxorubicin/Dactinomycin + Etoposide)31,32,34,35,40,41,f,g,i |
Day 1: Vincristine 1.5mg/m2 (maximum 2mg) IV over 5-10 minutes Days 1-3: Ifosfamide 3,000mg/m2 IV over 3 hours daily Days 1-3: Mesna 600mg/m2 IV over 15 minutes 3 times daily (once prior to ifosfamide, then at 4 and 8 hours from the start of each ifosfamide dose) Days 1-3: Doxorubicin 20mg/m2 IV push daily OR Days 1-3: Dactinomycin 500mcg/m2 IV push daily Days 1-3: Etoposide 150mg/m2 IV over 60 minutes daily. Repeat cycle every 3 weeks for 4-8 cycles (neoadjuvant) and 5-12 cycles (adjuvant) or 14 cycles (metastatic) of 8 cycles |
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▶Ewing Sarcoma Second-Line Therapy (Relapsed/Refractory or Metastatic Disease)1 |
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Preferred Regimens |
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Cyclophosphamide + Topotecan33,43-46,i,j |
Days 1-5: Cyclophosphamide 250mg/m2 IV over 30 minutes Days 1-5: Topotecan 0.75mg/m2 IV over 30 minutes. Repeat cycle every 3 weeks. |
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Irinotecan + Temozolomide47-50,j |
Days 1-5,8-12: Irinotecan 10-20mg/m2 IV over 90 minutes daily Days 1-5: Temozolomide 100mg/m2 orally once daily. Repeat cycle every 3 weeks. |
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Irinotecan + Temozolomide + Vincristine47-52 |
Days 1-5, 8-12: Irinotecan 10-20mg/m2 IV over 90 minutes daily Days 1-5: Temozolomide 100mg/m2 orally daily Day 1: Vincristine 1.5mg/m2 (maximum 2mg) IV over 5-10 minutes OR Days 1,8: Vincristine 1.5mg/m2 (maximum 2mg) IV over 5-10 minutes. Repeat cycle every 3 weeks. |
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Other Recommended Regimens |
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Cabozantinib53,54,c,l |
Days 1-28: Cabozantinib 60mg orally once daily. Repeat cycle every 4 weeks. |
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Docetaxel + Gemcitabine55-57,i,j |
Days 1,8: Gemcitabine 675mg/m2 IV at a rate of 10mg/m2 per minute, followed by: Day 8: Docetaxel 75-100mg/m2 IV over 60 minutes. Repeat cycle every 3 weeks. |
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Useful in Certain Circumstances |
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Ifosfamide + Carboplatin + Etoposide34,35,58,59,g,i-k |
Days 1-5: Ifosfamide 1,800mg/m2 IV daily Days 1-5: Mesna 360mg/m2 IV over 15 minutes three times daily — one dose before ifosfamide, then at 4 and 8 hours from the start of each ifosfamide dose) Days 1,2: Carboplatin 400mg/m2 IV daily Days 1-5: Etoposide 100mg/m2 IV daily. Repeat cycle every 3 weeks for up to 12 cycles. |
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▶Giant Cell Tumor of Bone |
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Preferred Regimen |
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Denosumab60-62 |
Days 1,8,15: Denosumab 120mg subcutaneous Administer for one 4-week cycle, followed by: Day 1: Denosumab 120mg subcutaneous. Repeat cycle every 4 weeks. |
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Useful in Certain Circumstances |
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Interferon Alfa 2B63-65 |
Days 1-28: Interferon alfa 2B 3million units/m2 subcutaneous daily (starting 48-72 hours post-surgery if involved). Repeat cycle every 4 weeks. |
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▶Osteosarcoma First-line Therapy (Primary/Neoadjuvant/Adjuvant Therapy or Metastatic Disease)1 |
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Preferred Regimens |
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Cisplatin + Doxorubicin (Category 1)21,32,66,d,i |
Day 1: Cisplatin 100mg/m2 IV continuous infusion over 24 hours Days 1-3: Doxorubicin 25mg/m2 IV continuous infusion over 24 hours daily. Repeat cycle every 3 weeks for 2 cycles (neoadjuvant) and 4 cycles (adjuvant) for a total of 6 cycles, or 6 cycles total (metastatic). |
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MAP High-Dose Methotrexate + Cisplatin + Doxorubicin (Category 1)21,32,67-69,d,i,m |
Days 1-2: Doxorubicin 37.5mg/m2 IV continuous infusion over 24 hours daily Days 1-2: Cisplatin 60mg/m2 IV over 60 minutes daily. Repeat weekly cycle on weeks 1 and 6 (neoadjuvant), followed by on weeks 12 and 17 (adjuvant), or on weeks 1, 6, 12, and 17 (metastatic). Days 1-2: Doxorubicin 37.5mg/m2 IV continuous infusion over 24 hours daily OR Day 1: Doxorubicin 75mg/m2 IV push. Repeat weekly cycle on weeks 22 and 26 (adjuvant or metastatic), with: Day 1: Methotrexate 12g/m2 (maximum 20g) IV over 4 hours Day 2: Leucovorin 15mg IV over 15 minutes starting 24 hours from initiation of methotrexate infusion and continuing every 6 hours until methotrexate level is less than 0.05 micromoles/L and at least total 8 doses. Repeat weekly cycle on weeks 4, 5, 9, and 10 (neoadjuvant), followed by: on weeks 15, 16, 20, 21, 24, 25, and 29 (adjuvant), or on weeks 4, 5, 9, 10, 15, 16, 20, 21, 24, 25, 28 and 29 (metastatic). |
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Other Recommended Regimens |
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Doxorubicin + Cisplatin + Ifosfamide + High-Dose Methotrexate21,32,34,67,70,d,g,m |
See NCCN Bone Cancer Guidelines1 |
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▶Osteosarcoma Second-line Therapy (Relapsed/Refractory or Metastatic Disease)1 |
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Preferred Regimens |
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Ifosfamide (High-Dose)34,71,72,g,i |
Days 1-5: Ifosfamide 2,000-2,800mg/m2 IV over 3 hours daily Days 1-5: Mesna 300-500mg/m2 IV over 15 minutes three times daily (one dose before ifosfamide, then at 4 and 8 hours from the start of each ifosfamide dose). Repeat cycle every 3 weeks. |
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Ifosfamide (High-Dose) + Etoposide34,35,71-73,g,i |
Days 1-5: Etoposide 100mg/m2 IV over 60 minutes daily Days 1-5: Ifosfamide 1,800mg/m2 IV over 3 hours daily Days 1-5: Mesna 360mg/m2 IV over 15 minutes 3 times daily (one dose before Ifosfamide, then at 4 and 8 hours from the start of each Ifosfamide dose). Repeat cycle every 3 weeks. |
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Regorafenib (Category 1)74,75,c |
Days 1-21: Regorafenib 160mg orally once daily. Repeat cycle every 4 weeks. |
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Sorafenib27-30,c,e |
Days 1-28: Sorafenib 400mg orally twice daily. Repeat cycle every 4 weeks. |
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Other Recommended Regimens |
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Cabozantinib53,54,c,l |
Days 1-28: Cabozantinib 60mg orally once daily. Repeat cycle every 4 weeks. |
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Cyclophosphamide + Topotecan33,43-46,i,j |
Days 1-5: Cyclophosphamide 250mg/m2 IV over 30 minutes Days 1-5: Topotecan 0.75mg/m2 IV over 30 minutes. Repeat cycle every 3 weeks. |
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Docetaxel + Gemcitabine55-57,i,j |
Days 1,8: Gemcitabine 675mg/m2 IV at a rate of 10mg/m2 per minute, followed by: Day 8: Docetaxel 75-100mg/m2 IV over 60 minutes. Repeat cycle every 3 weeks. |
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Gemcitabine56,76 |
Days 1,8: Gemcitabine 1,200mg/m2 IV at rate of 10mg/m2/minute. Repeat cycle every 3 weeks. |
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Sorafenib + Everolimus (Category 2B)27,77,78,c,e |
Days 1-28: Everolimus 5mg orally once daily Days 1-28: Sorafenib 400mg orally twice daily. Repeat cycle every 4 weeks. |
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Useful in Certain Circumstances |
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Cyclophosphamide + Etoposide33,35,79,i,n |
Day 1: Cyclophosphamide 4000mg/m2 IV over 3 hours daily Day 1: Mesna 1400mg/m2 IV before and after 4 hours and 8 hours from cyclophosphamide Days 2-4: Etoposide 100mg/m2 IV over 1 hour twice daily (total dose 600mg/m2). Repeat cycle every 3-4 weeks. |
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High-Dose Methotrexate67,68,80,m |
Day 1: Methotrexate 12g/m2 (maximum 20g) IV over 4 hours Day 2: Leucovorin 15mg IV over 15 minutes starting 24 hours from initiation of methotrexate infusion and continuing every 6 hours until methotrexate level is less than 0.05micromoles/L and at least total 8 doses. Repeat weekly cycle on weeks 1, 2, 3, 7, 8, 9, 13, 14, 15, 19, 20, and 21. |
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High-Dose Methotrexate + Etoposide + Ifosfamide34,35,67,80,g,i,m |
Day 1: Methotrexate 12g/m2 (maximum 20g) IV over 4 hours Day 2: Leucovorin 15mg IV over 15 minutes starting 24 hours from initiation of methotrexate infusion and continuing every 6 hours until methotrexate level <0.05micromoles/L and at least 8 total doses. Repeat cycle weekly on weeks 1, 2, 3, 7, 8, 9, 13, 14, 15, 19, 20, and 21. Days 1-4: Ifosfamide 3,000mg/m2 IV over 3 hours daily Days 1-4: Mesna 600mg/m2 IV over 15 minutes three times daily (one dose before ifosfamide, then at 4 and 8 hours from the start of each ifosfamide dose). Days 1-4: Etoposide 75mg/m2 IV over 60 minutes. Repeat cycle weekly on weeks 4, 10, 16, and 22. |
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Useful in Certain Circumstances |
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Ifosfamide + Carboplatin + Etoposide34,35,58,59,g,i,k |
Days 1-5: Ifosfamide 1,800mg/m2 IV daily Days 1-5: Mesna 360mg/m2 IV over 15 minutes three times daily — one dose before ifosfamide, then at 4 and 8 hours from the start of each ifosfamide dose) Days 1,2: Carboplatin 400mg/m2 IV daily Days 1-5: Etoposide 100mg/m2 IV daily. Repeat cycle every 3 weeks for up to 12 cycles. |
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Samarium-152 ethylene diamine tetramethylene phosphonate (for relapsed or refractory disease beyond second-line therapy)81,82 |
See NCCN Bone Cancer Guidelines1 |
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a Pembrolizumab is a systemic treatment option for adult and pediatric patients with unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options. Additional dosing recommendations follow: 200mg IV Day 1, repeat every 3 weeks or 400mg IV Day 1, repeat every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months for treatment of patients with MSI-H bone cancer. Not for Giant Cell Tumor of Bone or Chordoma. b TMB-H for patients unresectable or metastatic tumors who have progressed following prior treatment and who have no satisfactory alternative treatment options. Not for Giant Cell Tumor of Bone. c This agent has multiple potential drug-drug and/or drug-food interactions. Review patient medical profile and drug package insert for specific drug and food interactions and recommendations. d Hydration is required with supplemental electrolytes pre- and post-administration of cisplatin. e Sorafenib may cause cutaneous squamous cell carcinoma. Monitor for signs and symptoms of cutaneous squamous cell carcinoma prior to initiation of therapy and as clinically indicated. f Dactinomycin can be substituted for doxorubicin for concerns regarding cardiotoxicity. g Hydration is required pre- and post-administration of ifosfamide. h In patients younger than 18 years, evidence supports 2-week compressed treatment. i Administration with myeloid growth factor therapy is recommended. j Vincristine could be added to these regimens. k ICE regimen evaluated in patients 22.5 years of age or younger. l Cabozantinib (Cabometyx) tablets and cabozantinib (Cometriq) capsules are not interchangeable products. The dosage strengths of each product and dosing recommendations for specific indications differ. m In the event a patient receiving high-dose methotrexate experiences delayed elimination due to renal impairment, glucarpidase is strongly recommended. n Together with mesna all patients had hyperhydration (3000 mL/m2/day) during chemotherapy administration. |
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References |
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1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Hepatobiliary Cancers V.1.2021. Available at: https://www.nccn.org/professionals/physician_gls/pdf/bone.pdf. Accessed July 18, 2021. 2. Pembolizumab (Keytruda) [package insert]. Princeton, NJ: Bristol-Myers Squibb; 2020. 3. Tawbi HA, Burgess M, Bolejack V, et al. Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial. Lancet Oncol. 2017;18(11):1493-1501. 4. Le DT, Uram JN, Wang H, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372(26):2509-2520. 5. Lala M, Li TR, de Alwis DP, et al. A six-weekly dosing schedule for pembrolizumab in patients with cancer based on evaluation using modelling and simulation. Eur J Cancer. 2020;131:68-75. 6. Merino DM, McShane LM, Fabrizio D On behalf of the TMB harmonization consortium, et al. 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Results of a prospective phase 2 study of pazopanib in patients with surgically unresectable or metastatic chondrosarcoma. Cancer. 2020;126(1):105-111. 12. Ivosidenib (Tibsovo) [package insert]. Cambridge, MA: Agios Pharmaceuticals, Inc; 2021. 13. Tap WD, Villalobos VM, Cote GM, et al. Phase I study of the mutant IDH1 inhibitor ivosidenib: safety and clinical activity in patients with advanced chondrosarcoma. J Clin Oncol. 2020;38(15):1693-1701. 14. Imatinib (Gleevec) [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2020. 15. Casali PG, Messina A, Stacchiotti S, et al. Imatinib mesylate in chordoma. Cancer. 2004;101:2086-2097. 16. Stacchiotti S, Longhi A, Ferraresi V, et al. Phase II study of imatinib in advanced chordoma. J Clin Oncol. 2012;30(9):914-920. 17. Sunitinib (Sutent) [package insert]. New York, NY: Pfizer Labs; 2020. 18. George S, Merriam P, Maki RG, et al. 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