Therapy Detail
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| Therapy Name | Pazopanib + Trametinib |
| Synonyms | |
| Therapy Description | |
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| Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
|---|---|---|---|---|
| Pazopanib | Votrient | GW-786034 | FGFR1 Inhibitor 23 FGFR2 Inhibitor 16 FGFR3 Inhibitor 13 KIT Inhibitor 51 PDGFR Inhibitor (Pan) 27 VEGFR Inhibitor (Pan) 32 | Votrient (pazopanib) inhibits VEGFR-1, -2 and -3, KIT, and PDGFR, and FGFR1, 2, and 3, leading to decreased tumor angiogenesis and growth (PMID: 17620431, PMID: 23786770). Votrient (pazopanib) is approved for renal cell carcinoma and soft tissue sarcoma (FDA.gov). |
| Trametinib | Mekinist | GSK1120212 | MEK inhibitor (Pan) 22 MEK1 Inhibitor 20 MEK2 Inhibitor 18 | Mekinist (trametinib) inhibits MEK 1 and 2, which potentially leads to reduced tumor cell proliferation (PMID: 27956260). Mekinist (trametinib) is FDA approved for melanoma patients harboring BRAF V600E or BRAF V600K mutations, and in combination with Tafinlar (dabrafinib) for BRAF V600E/K-mutant melanoma, BRAF V600E- mutant non-small cell lung cancer, and BRAF V600E-mutant anaplastic thyroid cancer (FDA.gov). |
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| Unknown unknown | renal cell carcinoma | not applicable | Pazopanib + Trametinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, combination of Mekinist (trametinib) and Votrient (pazopanib) effectively inhibited tumor angiogenesis and growth in cell line xenograft models of renal cell carcinoma (PMID: 26487278). | 26487278 |
| Unknown unknown | differentiated thyroid gland carcinoma | not applicable | Pazopanib + Trametinib | Phase I | Actionable | In a Phase I trial, treatment with the combination of Votrient (pazopanib) and Mekinist (trametinib) was tolerable and resulted in an objective response rate of 33% (4/12, all partial responses), stable disease in 50% (5/12), a median progression-free survival (PFS) of 10.7 months, a 2-year PFS of 25%, and a median overall survival of 29.3 months in patients with differentiated thyroid cancer in the dose expansion cohort (PMID: 31186313; NCT01438554). | 31186313 |
| Unknown unknown | Advanced Solid Tumor | not applicable | Pazopanib + Trametinib | Phase I | Actionable | In a Phase I trial, combination treatment with Votrient (pazopanib) and Mekinist (trametinib) was tolerable and resulted in partial response in 12% (3/25), and stable disease in 72% (18/25) of patients with advanced solid tumors, and 9 patients remained on study for more than 6 cycles, including patients with differentiated thyroid cancer (n=3), colorectal cancer (n=2), melanoma (n=1), cholangiocarcinoma (n=1), ovarian cancer (n=1), and synovial cell sarcoma (n=1) (PMID: 31186313; NCT01438554). | 31186313 |
| Unknown unknown | sarcoma | no benefit | Pazopanib + Trametinib | Phase Ib/II | Actionable | In a Phase Ib/II trial, the combination of Votrient (pazopanib) and Mekinist (trametinib) demonstrated safety and resulted in partial response in 8% (2/25) and stable disease in 48% (12/25) of patients with advanced soft tissue sarcomas, but did not improve the 4 month progression-free survival rate over Votrient (pazopanib) alone (PMID: 28377484). | 28377484 |
| NRAS mutant | differentiated thyroid gland carcinoma | predicted - sensitive | Pazopanib + Trametinib | Phase I | Actionable | In a Phase I trial, of 10 differentiated thyroid cancer patients, 3 of 3 responders (all partial responses) to treatment with the combination of Votrient (pazopanib) and Mekinist (trametinib) harbored NRAS mutations, while none of the seven patients with stable disease or progressive disease had NRAS mutations (PMID: 31186313; NCT01438554). | 31186313 |
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| Clinical Trial | Phase | Therapies | Title | Recruitment Status |
|---|---|---|---|---|
| NCT01438554 | Phase I | Pazopanib + Trametinib | Phase 1 Study of Pazopanib With GSK1120212 in Advanced Solid Tumors, Enriched With Patients With Differentiated Thyroid Cancer, Soft-tissue Sarcoma, and Cholangiocarcinoma | Completed |
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