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Profile Name | VHL inact mut |
Gene Variant Detail | |
Relevant Treatment Approaches | mTORC1 Inhibitor VEGFR Inhibitor (Pan) VEGFR2 Inhibitor |
Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|---|
VHL inact mut | renal cell carcinoma | no benefit | Apitolisib | Case Reports/Case Series | Actionable | In a retrospective analysis from a Phase II clinical trial, patients with metastatic renal cell carcinoma treated with Apitolisib (GDC-0980) had no difference in progression-free survival when stratified by the presence (n=5) or absence (n=17) of deleterious VHL mutations (PMID: 26951309). | 26951309 | |
VHL inact mut | renal cell carcinoma | predicted - sensitive | mTORC1 Inhibitor | Everolimus | Case Reports/Case Series | Actionable | In a retrospective analysis from a Phase II clinical trial, patients with metastatic renal cell carcinoma treated with Afinitor (everolimus) had a trend towards improved in progression-free survival when stratified by the presence (median PFS=8.6 months, n=15) or absence (median PFS=5.5 months, n=16) of deleterious VHL mutations (PMID: 26951309). | 26951309 |
VHL inact mut | clear cell renal cell carcinoma | conflicting | PT2399 | Preclinical - Pdx | Actionable | In a preclinical study, PT2399 had variable impact on tumor growth in clear cell renal cell carcinoma (ccRCC) cell line and patient-derived xenograft (PDX) models with defective VHL, with decreased tumor growth in a VHL-defective ccRCC PDX model and some VHL-defective ccRCC cell line xenograft models, and no tumor suppression in other cell line xenograft models (PMID: 27595393). | 27595393 | |
VHL inact mut | renal cell carcinoma | predicted - sensitive | VEGFR Inhibitor (Pan) | Alpha 2 Interferon + Bevacizumab | Clinical Study - Cohort | Actionable | In a retrospective analysis, VHL alterations did not impact overall survival or objective response in renal cell carcinoma patients treated with a VEGF-targeted therapy, including Avastin (bevacizumab) and Alpha 2 Interferon combination therapy, but were associated with a prolonged time to progression (PMID: 16827904). | 16827904 |
VHL inact mut | islet cell tumor | not applicable | N/A | Guideline | Risk Factor | Germline inactivating mutations in VHL result in von Hippel-Lindau (VHL) syndrome, which is associated with increased risk of developing pancreatic neuroendocrine tumors (NCCN.org). | detail... | |
VHL inact mut | clear cell renal cell carcinoma | not applicable | N/A | Guideline | Risk Factor | Germline inactivating mutations in VHL result in von Hippel-Lindau (VHL) syndrome, which is associated with increased risk of developing clear cell renal cell carcinoma (NCCN.org). | detail... | |
VHL inact mut | renal cell carcinoma | sensitive | Belzutifan | FDA approved | Actionable | In a Phase II trial that supported FDA approval, Welireg (belzutifan) treatment was safe and resulted in a confirmed partial response (PR) in 36% (22/61) and unconfirmed PR in 11% (7/61) of patients with Von Hippel-Lindau disease-associated localized renal cell carcinoma harboring germline VHL mutations, median duration of response was not reached in responders (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 4555-4555; NCT03401788). | detail... detail... | |
VHL inact mut | hemangioblastoma | sensitive | Belzutifan | FDA approved | Actionable | In a Phase II trial (LITESPARK-004) that supported FDA approval, Welireg (belzutifan) treatment was safe and resulted in an objective response rate of 44% (22/61, 4 complete responses, 18 partial responses) in patients with Von Hippel-Lindau disease-associated CNS hemangioblastoma harboring germline VHL mutations, with a disease control rate of 90%, a median time to response of 5.4 months, and median progression-free survival not reached (J Clin Oncol 41, 2023 (suppl 16; abstr 2008); NCT03401788). | detail... detail... | |
VHL inact mut | pancreatic endocrine carcinoma | sensitive | Belzutifan | FDA approved | Actionable | In a Phase II trial that supported FDA approval, Welireg (belzutifan) treatment was safe and resulted in an overall response rate of 80% (16/20, 1 complete response, 15 partial responses) in patients with Von Hippel-Lindau disease-associated pancreatic neuroendocrine tumors harboring germline VHL mutations (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 4555-4555; NCT03401788). | detail... detail... | |
VHL inact mut | retinal hemangioblastoma | sensitive | Belzutifan | Phase II | Actionable | In a Phase II trial, Welireg (belzutifan) treatment was safe and resulted in an overall response rate of 32% (16/50, 1 complete response, 15 partial responses) in patients with Von Hippel-Lindau disease-associated CNS hemangioblastoma harboring germline VHL mutations, 69% (11/16) of patients with retinal hemangioblastoma experienced improvement (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 4555-4555; NCT03401788). | detail... | |
VHL inact mut | hemangioblastoma | sensitive | Belzutifan | Guideline | Actionable | Welireg (belzutifan) is included in guidelines for patients with Von Hippel-Lindau disease-associated CNS hemangioblastoma that do not require immediate surgery (NCCN.org). | detail... | |
VHL inact mut | renal cell carcinoma | sensitive | Belzutifan | Guideline | Actionable | Welireg (belzutifan) is included in guidelines for patients with Von Hippel-Lindau disease-associated renal cell carcinoma that do not require immediate surgery (NCCN.org). | detail... | |
VHL inact mut | renal cell carcinoma | sensitive | VEGFR Inhibitor (Pan) | Pazopanib | Phase II | Actionable | In a Phase II trial, Votrient (pazopanib) treatment resulted in an objective response rate of 42% (13/31, 13 partial responses) and stable disease in 58% of patients with Von Hippel-Lindau disease, with 75% (24/32) of the patients harboring confirmed VHL mutations; 52% (31/59, 2 complete and 29 partial responses) of target renal cell carcinomas responded to the treatment (PMID: 30236511; NCT01436227). | 30236511 |
VHL inact mut | renal cell carcinoma | sensitive | VEGFR Inhibitor (Pan) | Pazopanib | Guideline | Actionable | Votrient (pazopanib) is included in guidelines as systemic therapy for patients with renal cell carcinoma associated with Von Hippel-Lindau disease (NCCN.org). | detail... |
VHL inact mut | renal cell carcinoma | sensitive | Belzutifan | Guideline | Actionable | Welireg (belzutifan) is included in guidelines for patients with localized Von Hippel-Lindau disease-associated renal cell carcinoma harboring germline VHL mutations (PMID: 38788900; ESMO.org). | detail... 38788900 |