Table 1.
Clinical data on the use of anti-VEGF agents in osteosarcoma patients.
| Author | N (n = OST) | Phase | Type of Study | Drug | Control | Population | ORR | PFS (Months) | OS (Months) | Side Effects (Grade 3–4) | Additional Survival Data |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Duffaud et al. (2019) [43] | 38 (26) | 2 | Non-comparative, double blind, prospective, randomized | Regorafenib (160 mg daily for 21 days q28 days) | Placebo | Metastatic OST (10 years or older) after failure of 2 lines of therapy | 8% vs. 0 | 16.4 vs. 4.1 weeks | 11.3 vs. 5.9 | Hypertension (24% vs. 0%) and hand-foot reaction (10% vs. 0%) | PFS at 8 weeks (65% vs. 0) |
| Davis et al. (2019) [44] | 42 | 2 | Double blind, prospective, randomized | Regorafenib (160 mg daily for 21 days q28 days) | Placebo | Metastatic OST (10 years or older) after failure of 1 lines of therapy | 13.6 vs. 0 | 3.6 vs. 1.7 | 11.1 vs. 13.4 | hypertension (14%) followed by thrombocytopenia, hypophosphatemia, maculopapular rash and extremity pain (9% each) | PFS at 8 weeks (79 vs. 25) |
| Italiano et al. (2020) [56] | 90 (45) | 2 | Prospective, single arm | Cabozantinib (60 mg orally for a cycles of 28 days or 40 mg/m2 in <16 y) | NA | Recurrent or metastatic OST and Ewing sarcoma (10 years or older) | 12 | 6.7 | 10.6 | hypophosphatemia, elevated aspartate aminotransferase, palmar-plantar syndrome and neutropenia | 6-month non-progression = 33% |
| Grignani et al. (2012) [62] | 35 | 2 | Prospective, single arm | Sorafenib 400 mg twice daily until progression | NA | Relapsed or unresectable OST (>14 years) after standard therapy | 8 | 4 | 7 | anemia, thrombocytopenia (6%) | PFS at 4 months = 46% |
| Grignani et al. (2015) [66] | 38 | 2 | Prospective, single arm | Sorafenib 800 mg + everolimus 5 mg daily | NA | Relapsed or unresectable OST after standard therapy | 10 | 5 | 11 | lymphopenia, hypophosphatemia and hand–foot syndrome | PFS at 6 months = 45% |
| Martin-Broto et al. (2017) [69] | 35 | 2 | Prospective, single arm | Gemcitabine (800 mg/m2 on day 1 and 8 on a 21-day cycle) and rapamycin 5 mg daily | NA | Relapsed or unresectable OST after standard therapy | 6% | 2.3 | 7.1 | cytopenia and fatigue | PFS at 4 months = 44% |
| Penel-Page et al. (2015) [70] | 23 (18 combo) | NA | Retrospective | Sirolimus ± cyclophosphamide | NA | Relapsed OST after standard therapy | 13 | 3 | NA | PFS at 4 months = 40% | |
| Longhi et al. (2018) [75] | 15 | NA | Retrospective | Pazopanib 800 mg daily | NA | Metastatic or unresectable OST after standard therapy | 7 | 6 | 7 | Hypertension and thrombocytopenia (20% each) | |
| Agulnik et al. (2018) [76] | 139 (17) | 2 | Prospective, single arm | Pazopanib (800 mg daily) with topotecan (8 mg on day 1, 8 and 15) on a 28-days cycles | NA | Metastatic or unresectable OST after standard therapy | 6 | 4.5 | 11.1 | In all population: neutropenia (42), thrombocytopenia (29), hypertension (16) and anemia (12) | PFS at 3 months = 62.5% |
| Xie et al. (2019) [80] | 37 | 2 | Prospective, single arm | Apatinib (500 mg (body surface area) <1.5, or 750 mg if BSA ≥ 1.5) | NA | Relapsed or unresectable OST after standard therapy | 43.24 | 4.5 | 9.87 | pneumothorax (16.2%), palmo-plantar erythrodysesthesia syndrome (8.1%) wound dehiscence (10.8%), proteinuria (8.1%) and diarrhea (8.1%) | PFS at 4 months = 57% |
| Gaspar et al. (2018) [81] | 16 (P.2) and 7 (1b) | 1b–2 | Prospective, single arm | Lenvatinib 14 mg/m2 (P.2) or 11 mg/m2 in combination with ifosfamide 3 g/m2 and etoposide 100 mg/m2 days 1-3 (P.1b) | NA | Relapsed or unresectable OST after standard therapy | 6.25 (P.2) and 14.2 (P.1b) | NA | NA | Back pain and dyspnea (12.5% each) |
PFS: progression-free survival; OS: overall survival; NA: not applicable; OST: osteosarcoma; ORR: overall response rate.