Therapy Name | Palbociclib + Trametinib |
Therapy Description |
Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
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Palbociclib | Ibrance | PD0332991 | CDK4/6 Inhibitor 8 | Ibrance (palbociclib) is a selective inhibitor of cyclin-dependent kinase 4 (CDK4) and 6 (CDK6) (PMID: 19874578). Ibrance (palbociclib) is approved in combination with an aromatase inhibitor in postmenopausal patients with ER-positive, ERBB2 (HER2)-negative metastatic breast cancer, and in combination with Faslodex (fulvestrant) in patients with ER-positive, ERBB2 (HER2)-negative metastatic breast cancer (FDA.gov). |
Trametinib | Mekinist | GSK1120212 | MEK inhibitor (Pan) 20 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). |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References | KRAS G13D | colorectal cancer | sensitive | Palbociclib + Trametinib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, Mekinist (trametinib) and Ibrance (palbociclib) synergistically inhibited growth of colorectal cancer cells harboring KRAS G13D in culture and resulted in partial tumor regression in patient-derived xenograft models (PMID: 26369631). | 26369631 | BRAF wild-type | melanoma | decreased response | Palbociclib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, a BRAF wild-type melanoma cell line demonstrated minimal sensitivity when treated with the combination of Ibrance (palbociclib) and Mekinist (trametinib) in culture (PMID: 27488531). | 27488531 | NRAS wild-type | melanoma | decreased response | Palbociclib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, an NRAS wild-type melanoma cell line demonstrated minimal sensitivity when treated with the combination of Ibrance (palbociclib) and Mekinist (trametinib) in culture (PMID: 27488531). | 27488531 | BRAF mut RB1 loss | melanoma | decreased response | Palbociclib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line with a BRAF mutation and loss of RB1 demonstrated minimal sensitivity when treated with the combination of Ibrance (palbociclib) and Mekinist (trametinib) in culture (PMID: 27488531). | 27488531 | KRAS mutant | colorectal cancer | sensitive | Palbociclib + Trametinib | Preclinical - Pdx | Actionable | In a preclinical study, Mekinist (trametinib) and Ibrance (palbociclib) combination treatment resulted in objective response in PDX models of colorectal cancer cells harboring KRAS mutations (PMID: 26369631). | 26369631 | NRAS Q61K CDKN2A loss | melanoma | sensitive | Palbociclib + Trametinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Ibrance (palbociclib) and Mekinist (trametinib) induced tumor regression in a mouse melanoma model expressing NRAS Q61K and harboring CDKN2A loss (PMID: 22983396). | 22983396 | BRAF mutant | melanoma | sensitive | Palbociclib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring a BRAF mutation demonstrated greater sensitivity to the combination treatment of Mekinist (trametinib) and Ibrance (palbociclib) in culture when compared to either agent alone (PMID: 27488531). | 27488531 | BRAF V600E KRAS wild-type | colorectal cancer | no benefit | Palbociclib + Trametinib | Preclinical - Pdx | Actionable | In a preclinical study, Mekinist (trametinib) and Ibrance (palbociclib) combination treatment did not result in enhanced antitumor activity compared to Ibrance (palbociclib) alone in PDX models of KRAS wild-type colorectal cancer harboring BRAF V600E (PMID: 26369631). | 26369631 |
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Clinical Trial | Phase | Therapies | Title | Recruitment Status |
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NCT02065063 | Phase I | Palbociclib + Trametinib | A Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Anti-Cancer Activity of Trametinib in Combination With Palbociclib in Subjects With Solid Tumors | Completed |