Issue
Date Log
Copyright (c) 2025 Maram Awad Alhazimi, Mohammed Atallah Almasoudi, Mohammed Ali Mohammed Adawi, Fatmah Diva Uddin Ghazali, Abdullah Ali Mohammad Albahli, Shurug Saad Masoud Alkrini, Shaima Abdullah Bukhamsin, Abdullah Mohammed Ogdi, Aljouharah Saad Fahad Alhammad, Mohammed Abdullah Obaisan Alotaibi, Sabah Hamoud O Alsuwat
This work is licensed under a Creative Commons Attribution 4.0 International License.
Vemurafenib: Pharmacologic Profile, Clinical Applications, and Management in Primary Care and Family Medicine
Corresponding Author(s) : Maram Awad Alhazimi
Saudi Journal of Medicine and Public Health,
Vol. 2 No. 2 (2025)
Abstract
Background: Mutations within the mitogen-activated protein kinase (MAPK) pathway—particularly BRAF V600 mutations—play a central role in the pathogenesis of malignant melanoma and other malignancies. These mutations drive uncontrolled cellular proliferation and tumor progression. Vemurafenib, a selective BRAF inhibitor, represents a landmark advancement in targeted oncologic therapy.
Aim: This review aims to summarize the pharmacologic profile, clinical indications, safety considerations, and monitoring requirements of vemurafenib, with emphasis on its relevance to primary care and family medicine practice.
Methods: A narrative review was conducted using data from pivotal clinical trials, FDA approvals, and clinical guideline recommendations addressing vemurafenib’s efficacy, pharmacokinetics, adverse effects, contraindications, and monitoring strategies.
Results: Vemurafenib demonstrated significant improvements in overall and progression-free survival in patients with BRAF V600E–mutated metastatic melanoma compared with dacarbazine. Common adverse effects include dermatologic toxicity, photosensitivity, QT prolongation, hepatotoxicity, nephrotoxicity, and secondary cutaneous malignancies. Resistance mechanisms frequently develop, supporting the use of combination therapy with MEK inhibitors.
Conclusion: Vemurafenib remains a critical component of precision oncology for BRAF V600–mutant malignancies. Safe and effective use requires careful patient selection, interdisciplinary collaboration, proactive monitoring, and patient education to optimize outcomes and minimize toxicity.
Keywords
Download Citation
Endnote/Zotero/Mendeley (RIS)BibTeX
- Rapp UR, Goldsborough MD, Mark GE, Bonner TI, Groffen J, Reynolds FH, Stephenson JR. Structure and biological activity of v-raf, a unique oncogene transduced by a retrovirus. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4218-22.
- Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W, Davis N, Dicks E, Ewing R, Floyd Y, Gray K, Hall S, Hawes R, Hughes J, Kosmidou V, Menzies A, Mould C, Parker A, Stevens C, Watt S, Hooper S, Wilson R, Jayatilake H, Gusterson BA, Cooper C, Shipley J, Hargrave D, Pritchard-Jones K, Maitland N, Chenevix-Trench G, Riggins GJ, Bigner DD, Palmieri G, Cossu A, Flanagan A, Nicholson A, Ho JW, Leung SY, Yuen ST, Weber BL, Seigler HF, Darrow TL, Paterson H, Marais R, Marshall CJ, Wooster R, Stratton MR, Futreal PA. Mutations of the BRAF gene in human cancer. Nature. 2002 Jun 27;417(6892):949-54.
- Lee B, Mukhi N, Liu D. Current management and novel agents for malignant melanoma. J Hematol Oncol. 2012 Feb 14;5:3.
- Cohen Y, Xing M, Mambo E, Guo Z, Wu G, Trink B, Beller U, Westra WH, Ladenson PW, Sidransky D. BRAF mutation in papillary thyroid carcinoma. J Natl Cancer Inst. 2003 Apr 16;95(8):625-7.
- Huang T, Zhuge J, Zhang WW. Sensitive detection of BRAF V600E mutation by Amplification Refractory Mutation System (ARMS)-PCR. Biomark Res. 2013 Jan 16;1(1):3.
- Ziai J, Hui P. BRAF mutation testing in clinical practice. Expert Rev Mol Diagn. 2012 Mar;12(2):127-38.
- Xing M, Alzahrani AS, Carson KA, Viola D, Elisei R, Bendlova B, Yip L, Mian C, Vianello F, Tuttle RM, Robenshtok E, Fagin JA, Puxeddu E, Fugazzola L, Czarniecka A, Jarzab B, O'Neill CJ, Sywak MS, Lam AK, Riesco-Eizaguirre G, Santisteban P, Nakayama H, Tufano RP, Pai SI, Zeiger MA, Westra WH, Clark DP, Clifton-Bligh R, Sidransky D, Ladenson PW, Sykorova V. Association between BRAF V600E mutation and mortality in patients with papillary thyroid cancer. JAMA. 2013 Apr 10;309(14):1493-501.
- Proietti I, Skroza N, Michelini S, Mambrin A, Balduzzi V, Bernardini N, Marchesiello A, Tolino E, Volpe S, Maddalena P, Di Fraia M, Mangino G, Romeo G, Potenza C. BRAF Inhibitors: Molecular Targeting and Immunomodulatory Actions. Cancers (Basel). 2020 Jul 07;12(7)
- Flaherty KT, Puzanov I, Kim KB, Ribas A, McArthur GA, Sosman JA, O'Dwyer PJ, Lee RJ, Grippo JF, Nolop K, Chapman PB. Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med. 2010 Aug 26;363(9):809-19.
- Sosman JA, Kim KB, Schuchter L, Gonzalez R, Pavlick AC, Weber JS, McArthur GA, Hutson TE, Moschos SJ, Flaherty KT, Hersey P, Kefford R, Lawrence D, Puzanov I, Lewis KD, Amaravadi RK, Chmielowski B, Lawrence HJ, Shyr Y, Ye F, Li J, Nolop KB, Lee RJ, Joe AK, Ribas A. Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib. N Engl J Med. 2012 Feb 23;366(8):707-14.
- Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, Dummer R, Garbe C, Testori A, Maio M, Hogg D, Lorigan P, Lebbe C, Jouary T, Schadendorf D, Ribas A, O'Day SJ, Sosman JA, Kirkwood JM, Eggermont AM, Dreno B, Nolop K, Li J, Nelson B, Hou J, Lee RJ, Flaherty KT, McArthur GA., BRIM-3 Study Group. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011 Jun 30;364(26):2507-16.
- Seth R, Agarwala SS, Messersmith H, Alluri KC, Ascierto PA, Atkins MB, Bollin K, Chacon M, Davis N, Faries MB, Funchain P, Gold JS, Guild S, Gyorki DE, Kaur V, Khushalani NI, Kirkwood JM, McQuade JL, Meyers MO, Provenzano A, Robert C, Santinami M, Sehdev A, Sondak VK, Spurrier G, Swami U, Truong TG, Tsai KK, van Akkooi A, Weber J. Systemic Therapy for Melanoma: ASCO Guideline Update. J Clin Oncol. 2023 Oct 20;41(30):4794-4820.
- Jarab AS, Al-Qerem WA, Khdour LM, Mimi YA, Khdour MR. New emerging treatment options for metastatic melanoma: a systematic review and meta-analysis of skin cancer therapies. Arch Dermatol Res. 2024 Nov 01;316(10):735.
- Haroche J, Cohen-Aubart F, Emile JF, Maksud P, Drier A, Tolédano D, Barete S, Charlotte F, Cluzel P, Donadieu J, Benameur N, Grenier PA, Besnard S, Ory JP, Lifermann F, Idbaih A, Granel B, Graffin B, Hervier B, Arnaud L, Amoura Z. Reproducible and sustained efficacy of targeted therapy with vemurafenib in patients with BRAF(V600E)-mutated Erdheim-Chester disease. J Clin Oncol. 2015 Feb 10;33(5):411-8.
- Kulkarni AM, Gayam PKR, Aranjani JM. Advances in Understanding and Management of Erdheim-Chester Disease. Life Sci. 2024 Jul 01;348:122692.
- Forschner A, Niessner H, Bauer J, Bender B, Garbe C, Meier F. Successful treatment with vemurafenib in BRAF V600K-positive cerebral melanoma metastasis. JAMA Dermatol. 2013 May;149(5):642-4.
- Planchard D, Kim TM, Mazieres J, Quoix E, Riely G, Barlesi F, Souquet PJ, Smit EF, Groen HJ, Kelly RJ, Cho BC, Socinski MA, Pandite L, Nase C, Ma B, D'Amelio A, Mookerjee B, Curtis CM, Johnson BE. Dabrafenib in patients with BRAF(V600E)-positive advanced non-small-cell lung cancer: a single-arm, multicentre, open-label, phase 2 trial. Lancet Oncol. 2016 May;17(5):642-50.
- Brose MS, Cabanillas ME, Cohen EE, Wirth LJ, Riehl T, Yue H, Sherman SI, Sherman EJ. Vemurafenib in patients with BRAF(V600E)-positive metastatic or unresectable papillary thyroid cancer refractory to radioactive iodine: a non-randomised, multicentre, open-label, phase 2 trial. Lancet Oncol. 2016 Sep;17(9):1272-82.
- Tiacci E, De Carolis L, Simonetti E, Capponi M, Ambrosetti A, Lucia E, Antolino A, Pulsoni A, Ferrari S, Zinzani PL, Ascani S, Perriello VM, Rigacci L, Gaidano G, Della Seta R, Frattarelli N, Falcucci P, Foà R, Visani G, Zaja F, Falini B. Vemurafenib plus Rituximab in Refractory or Relapsed Hairy-Cell Leukemia. N Engl J Med. 2021 May 13;384(19):1810-1823.
- Yiğit Kaya S, Mutlu YG, Malkan ÜY, Mehtap Ö, Keklik Karadağ F, Korkmaz G, Elverdi T, Saydam G, Özet G, Ar MC, Melek E, Maral S, Kaynar L, Sevindik ÖG. Single agent vemurafenib or rituximab-vemurafenib combination for the treatment of relapsed/refractory hairy cell leukemia, a multicenter experience. Leuk Res. 2024 May;140:107495.
- Tsai J, Lee JT, Wang W, Zhang J, Cho H, Mamo S, Bremer R, Gillette S, Kong J, Haass NK, Sproesser K, Li L, Smalley KS, Fong D, Zhu YL, Marimuthu A, Nguyen H, Lam B, Liu J, Cheung I, Rice J, Suzuki Y, Luu C, Settachatgul C, Shellooe R, Cantwell J, Kim SH, Schlessinger J, Zhang KY, West BL, Powell B, Habets G, Zhang C, Ibrahim PN, Hirth P, Artis DR, Herlyn M, Bollag G. Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity. Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):3041-6.
- Li Y, Zeng H, Qi C, Tan S, Huang Q, Pu X, Li W, Planchard D, Tian P. Features and efficacy of triple-targeted therapy for patients with EGFR-mutant non-small-cell lung cancer with acquired BRAF alterations who are resistant to epidermal growth factor receptor tyrosine kinase inhibitors. ESMO Open. 2024 Oct;9(10):103935.
- Larkin J, Ascierto PA, Dréno B, Atkinson V, Liszkay G, Maio M, Mandalà M, Demidov L, Stroyakovskiy D, Thomas L, de la Cruz-Merino L, Dutriaux C, Garbe C, Sovak MA, Chang I, Choong N, Hack SP, McArthur GA, Ribas A. Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N Engl J Med. 2014 Nov 13;371(20):1867-76.
- Boz Er AB, Sheldrake HM, Sutherland M. Overcoming Vemurafenib Resistance in Metastatic Melanoma: Targeting Integrins to Improve Treatment Efficacy. Int J Mol Sci. 2024 Jul 20;25(14)
- LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. National Institute of Diabetes and Digestive and Kidney Diseases; Bethesda (MD): Jun 28, 2018. Vemurafenib.
- Nazarian R, Shi H, Wang Q, Kong X, Koya RC, Lee H, Chen Z, Lee MK, Attar N, Sazegar H, Chodon T, Nelson SF, McArthur G, Sosman JA, Ribas A, Lo RS. Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation. Nature. 2010 Dec 16;468(7326):973-7.
- Maleka A, Enblad G, Sjörs G, Lindqvist A, Ullenhag GJ. Treatment of metastatic malignant melanoma with vemurafenib during pregnancy. J Clin Oncol. 2013 Apr 10;31(11):e192-3.
- de Haan J, van Thienen JV, Casaer M, Hannivoort RA, Van Calsteren K, van Tuyl M, van Gerwen MM, Debeer A, Amant F, Painter RC. Severe Adverse Reaction to Vemurafenib in a Pregnant Woman with Metastatic Melanoma. Case Rep Oncol. 2018 Jan-Apr;11(1):119-124.
- Pagan M, Jinks H, Sewell M. Treatment of metastatic malignant melanoma during pregnancy with a BRAF kinase inhibitor. Case Rep Womens Health. 2019 Oct;24:e00142.
- Drugs and Lactation Database (LactMed®) [Internet]. National Institute of Child Health and Human Development; Bethesda (MD): Dec 3, 2018. Vemurafenib.
- Robert C, Soria JC, Spatz A, Le Cesne A, Malka D, Pautier P, Wechsler J, Lhomme C, Escudier B, Boige V, Armand JP, Le Chevalier T. Cutaneous side-effects of kinase inhibitors and blocking antibodies. Lancet Oncol. 2005 Jul;6(7):491-500.
- Carlos G, Anforth R, Clements A, Menzies AM, Carlino MS, Chou S, Fernandez-Peñas P. Cutaneous Toxic Effects of BRAF Inhibitors Alone and in Combination With MEK Inhibitors for Metastatic Melanoma. JAMA Dermatol. 2015 Oct;151(10):1103-9.
- Porta-Sánchez A, Gilbert C, Spears D, Amir E, Chan J, Nanthakumar K, Thavendiranathan P. Incidence, Diagnosis, and Management of QT Prolongation Induced by Cancer Therapies: A Systematic Review. J Am Heart Assoc. 2017 Dec 07;6(12)
- Chan SW, Vorobiof DA. Dupuytren's contractures associated with the BRAF inhibitor vemurafenib: a case report. J Med Case Rep. 2015 Jul 08;9:158.
- Chung SY, Shen JG, Ghiuzeli CM. Vemurafenib-induced pancreatitis in a patient with recurrent hairy cell leukaemia. BMJ Case Rep. 2020 Sep 14;13(9)
- Zhang W, McIntyre C, Riehl T, Forbes H, Bertran E, Choi HJ, Lee DH, Lee J. Effect of Vemurafenib on the Pharmacokinetics of a Single Dose of Tizanidine (a CYP1A2 Substrate) in Patients With BRAFV600 Mutation-Positive Malignancies. Clin Pharmacol Drug Dev. 2020 Jul;9(5):651-658.
- Zhang W, McIntyre C, Kuhn M, Forbes H, Kim TM, Lee J, Demidov L, Colburn D. Effect of Vemurafenib on the Pharmacokinetics of a Single Dose of Digoxin in Patients With BRAFV600 Mutation-Positive Metastatic Malignancy. J Clin Pharmacol. 2018 Aug;58(8):1067-1073.
- Rana J, Maloney NJ, Rieger KE, Pugliese SB, Strelo JL, Liu A, Zaba LC, Kwong BY. Drug-induced hypersensitivity syndrome like reaction with angioedema and hypotension associated with BRAF inhibitor use and antecedent immune checkpoint therapy. JAAD Case Rep. 2021 Jul;13:147-151.
- Chen P, Chen F, Zhou B. Systematic review and meta-analysis of prevalence of dermatological toxicities associated with vemurafenib treatment in patients with melanoma. Clin Exp Dermatol. 2019 Apr;44(3):243-251.
- Flor D, Pedroso M, Coutinho I, Gonçalo M. Toxic epidermal necrolysis caused by vemurafenib in a metastatic malignant melanoma. BMJ Case Rep. 2025 Feb 16;18(2)
- Dugauquier A, Awada AH, Motulsky E, Kisma N. INTRAVITREAL METHOTREXATE IN VEMURAFENIB-INDUCED UVEITIS. Retin Cases Brief Rep. 2024 Jul 01;18(4):455-458.
- Conen K, Mosna-Firlejczyk K, Rochlitz C, Wicki A, Itin P, Arnold AW, Gross M, Zimmermann F, Zippelius A. Vemurafenib-induced radiation recall dermatitis: case report and review of the literature. Dermatology. 2015;230(1):1-4.
- Sanagawa A, Takase H. Increased Mitochondrial Superoxide Level Is Partially Associated With Vemurafenib-Induced Renal Tubular Toxicity. Basic Clin Pharmacol Toxicol. 2025 Apr;136(4):e70015.
- Wanchoo R, Jhaveri KD, Deray G, Launay-Vacher V. Renal effects of BRAF inhibitors: a systematic review by the Cancer and the Kidney International Network. Clin Kidney J. 2016 Apr;9(2):245-51.
- Hwang JP, Feld JJ, Hammond SP, Wang SH, Alston-Johnson DE, Cryer DR, Hershman DL, Loehrer AP, Sabichi AL, Symington BE, Terrault N, Wong ML, Somerfield MR, Artz AS. Hepatitis B Virus Screening and Management for Patients With Cancer Prior to Therapy: ASCO Provisional Clinical Opinion Update. J Clin Oncol. 2020 Nov 01;38(31):3698-3715.
- Liu X, Solebo AL, Keane PA, Moore DJ, Denniston AK. Instrument-based tests for measuring anterior chamber cells in uveitis: a systematic review protocol. Syst Rev. 2019 Jan 22;8(1):30.
References
Rapp UR, Goldsborough MD, Mark GE, Bonner TI, Groffen J, Reynolds FH, Stephenson JR. Structure and biological activity of v-raf, a unique oncogene transduced by a retrovirus. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4218-22.
Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W, Davis N, Dicks E, Ewing R, Floyd Y, Gray K, Hall S, Hawes R, Hughes J, Kosmidou V, Menzies A, Mould C, Parker A, Stevens C, Watt S, Hooper S, Wilson R, Jayatilake H, Gusterson BA, Cooper C, Shipley J, Hargrave D, Pritchard-Jones K, Maitland N, Chenevix-Trench G, Riggins GJ, Bigner DD, Palmieri G, Cossu A, Flanagan A, Nicholson A, Ho JW, Leung SY, Yuen ST, Weber BL, Seigler HF, Darrow TL, Paterson H, Marais R, Marshall CJ, Wooster R, Stratton MR, Futreal PA. Mutations of the BRAF gene in human cancer. Nature. 2002 Jun 27;417(6892):949-54.
Lee B, Mukhi N, Liu D. Current management and novel agents for malignant melanoma. J Hematol Oncol. 2012 Feb 14;5:3.
Cohen Y, Xing M, Mambo E, Guo Z, Wu G, Trink B, Beller U, Westra WH, Ladenson PW, Sidransky D. BRAF mutation in papillary thyroid carcinoma. J Natl Cancer Inst. 2003 Apr 16;95(8):625-7.
Huang T, Zhuge J, Zhang WW. Sensitive detection of BRAF V600E mutation by Amplification Refractory Mutation System (ARMS)-PCR. Biomark Res. 2013 Jan 16;1(1):3.
Ziai J, Hui P. BRAF mutation testing in clinical practice. Expert Rev Mol Diagn. 2012 Mar;12(2):127-38.
Xing M, Alzahrani AS, Carson KA, Viola D, Elisei R, Bendlova B, Yip L, Mian C, Vianello F, Tuttle RM, Robenshtok E, Fagin JA, Puxeddu E, Fugazzola L, Czarniecka A, Jarzab B, O'Neill CJ, Sywak MS, Lam AK, Riesco-Eizaguirre G, Santisteban P, Nakayama H, Tufano RP, Pai SI, Zeiger MA, Westra WH, Clark DP, Clifton-Bligh R, Sidransky D, Ladenson PW, Sykorova V. Association between BRAF V600E mutation and mortality in patients with papillary thyroid cancer. JAMA. 2013 Apr 10;309(14):1493-501.
Proietti I, Skroza N, Michelini S, Mambrin A, Balduzzi V, Bernardini N, Marchesiello A, Tolino E, Volpe S, Maddalena P, Di Fraia M, Mangino G, Romeo G, Potenza C. BRAF Inhibitors: Molecular Targeting and Immunomodulatory Actions. Cancers (Basel). 2020 Jul 07;12(7)
Flaherty KT, Puzanov I, Kim KB, Ribas A, McArthur GA, Sosman JA, O'Dwyer PJ, Lee RJ, Grippo JF, Nolop K, Chapman PB. Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med. 2010 Aug 26;363(9):809-19.
Sosman JA, Kim KB, Schuchter L, Gonzalez R, Pavlick AC, Weber JS, McArthur GA, Hutson TE, Moschos SJ, Flaherty KT, Hersey P, Kefford R, Lawrence D, Puzanov I, Lewis KD, Amaravadi RK, Chmielowski B, Lawrence HJ, Shyr Y, Ye F, Li J, Nolop KB, Lee RJ, Joe AK, Ribas A. Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib. N Engl J Med. 2012 Feb 23;366(8):707-14.
Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, Dummer R, Garbe C, Testori A, Maio M, Hogg D, Lorigan P, Lebbe C, Jouary T, Schadendorf D, Ribas A, O'Day SJ, Sosman JA, Kirkwood JM, Eggermont AM, Dreno B, Nolop K, Li J, Nelson B, Hou J, Lee RJ, Flaherty KT, McArthur GA., BRIM-3 Study Group. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011 Jun 30;364(26):2507-16.
Seth R, Agarwala SS, Messersmith H, Alluri KC, Ascierto PA, Atkins MB, Bollin K, Chacon M, Davis N, Faries MB, Funchain P, Gold JS, Guild S, Gyorki DE, Kaur V, Khushalani NI, Kirkwood JM, McQuade JL, Meyers MO, Provenzano A, Robert C, Santinami M, Sehdev A, Sondak VK, Spurrier G, Swami U, Truong TG, Tsai KK, van Akkooi A, Weber J. Systemic Therapy for Melanoma: ASCO Guideline Update. J Clin Oncol. 2023 Oct 20;41(30):4794-4820.
Jarab AS, Al-Qerem WA, Khdour LM, Mimi YA, Khdour MR. New emerging treatment options for metastatic melanoma: a systematic review and meta-analysis of skin cancer therapies. Arch Dermatol Res. 2024 Nov 01;316(10):735.
Haroche J, Cohen-Aubart F, Emile JF, Maksud P, Drier A, Tolédano D, Barete S, Charlotte F, Cluzel P, Donadieu J, Benameur N, Grenier PA, Besnard S, Ory JP, Lifermann F, Idbaih A, Granel B, Graffin B, Hervier B, Arnaud L, Amoura Z. Reproducible and sustained efficacy of targeted therapy with vemurafenib in patients with BRAF(V600E)-mutated Erdheim-Chester disease. J Clin Oncol. 2015 Feb 10;33(5):411-8.
Kulkarni AM, Gayam PKR, Aranjani JM. Advances in Understanding and Management of Erdheim-Chester Disease. Life Sci. 2024 Jul 01;348:122692.
Forschner A, Niessner H, Bauer J, Bender B, Garbe C, Meier F. Successful treatment with vemurafenib in BRAF V600K-positive cerebral melanoma metastasis. JAMA Dermatol. 2013 May;149(5):642-4.
Planchard D, Kim TM, Mazieres J, Quoix E, Riely G, Barlesi F, Souquet PJ, Smit EF, Groen HJ, Kelly RJ, Cho BC, Socinski MA, Pandite L, Nase C, Ma B, D'Amelio A, Mookerjee B, Curtis CM, Johnson BE. Dabrafenib in patients with BRAF(V600E)-positive advanced non-small-cell lung cancer: a single-arm, multicentre, open-label, phase 2 trial. Lancet Oncol. 2016 May;17(5):642-50.
Brose MS, Cabanillas ME, Cohen EE, Wirth LJ, Riehl T, Yue H, Sherman SI, Sherman EJ. Vemurafenib in patients with BRAF(V600E)-positive metastatic or unresectable papillary thyroid cancer refractory to radioactive iodine: a non-randomised, multicentre, open-label, phase 2 trial. Lancet Oncol. 2016 Sep;17(9):1272-82.
Tiacci E, De Carolis L, Simonetti E, Capponi M, Ambrosetti A, Lucia E, Antolino A, Pulsoni A, Ferrari S, Zinzani PL, Ascani S, Perriello VM, Rigacci L, Gaidano G, Della Seta R, Frattarelli N, Falcucci P, Foà R, Visani G, Zaja F, Falini B. Vemurafenib plus Rituximab in Refractory or Relapsed Hairy-Cell Leukemia. N Engl J Med. 2021 May 13;384(19):1810-1823.
Yiğit Kaya S, Mutlu YG, Malkan ÜY, Mehtap Ö, Keklik Karadağ F, Korkmaz G, Elverdi T, Saydam G, Özet G, Ar MC, Melek E, Maral S, Kaynar L, Sevindik ÖG. Single agent vemurafenib or rituximab-vemurafenib combination for the treatment of relapsed/refractory hairy cell leukemia, a multicenter experience. Leuk Res. 2024 May;140:107495.
Tsai J, Lee JT, Wang W, Zhang J, Cho H, Mamo S, Bremer R, Gillette S, Kong J, Haass NK, Sproesser K, Li L, Smalley KS, Fong D, Zhu YL, Marimuthu A, Nguyen H, Lam B, Liu J, Cheung I, Rice J, Suzuki Y, Luu C, Settachatgul C, Shellooe R, Cantwell J, Kim SH, Schlessinger J, Zhang KY, West BL, Powell B, Habets G, Zhang C, Ibrahim PN, Hirth P, Artis DR, Herlyn M, Bollag G. Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity. Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):3041-6.
Li Y, Zeng H, Qi C, Tan S, Huang Q, Pu X, Li W, Planchard D, Tian P. Features and efficacy of triple-targeted therapy for patients with EGFR-mutant non-small-cell lung cancer with acquired BRAF alterations who are resistant to epidermal growth factor receptor tyrosine kinase inhibitors. ESMO Open. 2024 Oct;9(10):103935.
Larkin J, Ascierto PA, Dréno B, Atkinson V, Liszkay G, Maio M, Mandalà M, Demidov L, Stroyakovskiy D, Thomas L, de la Cruz-Merino L, Dutriaux C, Garbe C, Sovak MA, Chang I, Choong N, Hack SP, McArthur GA, Ribas A. Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N Engl J Med. 2014 Nov 13;371(20):1867-76.
Boz Er AB, Sheldrake HM, Sutherland M. Overcoming Vemurafenib Resistance in Metastatic Melanoma: Targeting Integrins to Improve Treatment Efficacy. Int J Mol Sci. 2024 Jul 20;25(14)
LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. National Institute of Diabetes and Digestive and Kidney Diseases; Bethesda (MD): Jun 28, 2018. Vemurafenib.
Nazarian R, Shi H, Wang Q, Kong X, Koya RC, Lee H, Chen Z, Lee MK, Attar N, Sazegar H, Chodon T, Nelson SF, McArthur G, Sosman JA, Ribas A, Lo RS. Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation. Nature. 2010 Dec 16;468(7326):973-7.
Maleka A, Enblad G, Sjörs G, Lindqvist A, Ullenhag GJ. Treatment of metastatic malignant melanoma with vemurafenib during pregnancy. J Clin Oncol. 2013 Apr 10;31(11):e192-3.
de Haan J, van Thienen JV, Casaer M, Hannivoort RA, Van Calsteren K, van Tuyl M, van Gerwen MM, Debeer A, Amant F, Painter RC. Severe Adverse Reaction to Vemurafenib in a Pregnant Woman with Metastatic Melanoma. Case Rep Oncol. 2018 Jan-Apr;11(1):119-124.
Pagan M, Jinks H, Sewell M. Treatment of metastatic malignant melanoma during pregnancy with a BRAF kinase inhibitor. Case Rep Womens Health. 2019 Oct;24:e00142.
Drugs and Lactation Database (LactMed®) [Internet]. National Institute of Child Health and Human Development; Bethesda (MD): Dec 3, 2018. Vemurafenib.
Robert C, Soria JC, Spatz A, Le Cesne A, Malka D, Pautier P, Wechsler J, Lhomme C, Escudier B, Boige V, Armand JP, Le Chevalier T. Cutaneous side-effects of kinase inhibitors and blocking antibodies. Lancet Oncol. 2005 Jul;6(7):491-500.
Carlos G, Anforth R, Clements A, Menzies AM, Carlino MS, Chou S, Fernandez-Peñas P. Cutaneous Toxic Effects of BRAF Inhibitors Alone and in Combination With MEK Inhibitors for Metastatic Melanoma. JAMA Dermatol. 2015 Oct;151(10):1103-9.
Porta-Sánchez A, Gilbert C, Spears D, Amir E, Chan J, Nanthakumar K, Thavendiranathan P. Incidence, Diagnosis, and Management of QT Prolongation Induced by Cancer Therapies: A Systematic Review. J Am Heart Assoc. 2017 Dec 07;6(12)
Chan SW, Vorobiof DA. Dupuytren's contractures associated with the BRAF inhibitor vemurafenib: a case report. J Med Case Rep. 2015 Jul 08;9:158.
Chung SY, Shen JG, Ghiuzeli CM. Vemurafenib-induced pancreatitis in a patient with recurrent hairy cell leukaemia. BMJ Case Rep. 2020 Sep 14;13(9)
Zhang W, McIntyre C, Riehl T, Forbes H, Bertran E, Choi HJ, Lee DH, Lee J. Effect of Vemurafenib on the Pharmacokinetics of a Single Dose of Tizanidine (a CYP1A2 Substrate) in Patients With BRAFV600 Mutation-Positive Malignancies. Clin Pharmacol Drug Dev. 2020 Jul;9(5):651-658.
Zhang W, McIntyre C, Kuhn M, Forbes H, Kim TM, Lee J, Demidov L, Colburn D. Effect of Vemurafenib on the Pharmacokinetics of a Single Dose of Digoxin in Patients With BRAFV600 Mutation-Positive Metastatic Malignancy. J Clin Pharmacol. 2018 Aug;58(8):1067-1073.
Rana J, Maloney NJ, Rieger KE, Pugliese SB, Strelo JL, Liu A, Zaba LC, Kwong BY. Drug-induced hypersensitivity syndrome like reaction with angioedema and hypotension associated with BRAF inhibitor use and antecedent immune checkpoint therapy. JAAD Case Rep. 2021 Jul;13:147-151.
Chen P, Chen F, Zhou B. Systematic review and meta-analysis of prevalence of dermatological toxicities associated with vemurafenib treatment in patients with melanoma. Clin Exp Dermatol. 2019 Apr;44(3):243-251.
Flor D, Pedroso M, Coutinho I, Gonçalo M. Toxic epidermal necrolysis caused by vemurafenib in a metastatic malignant melanoma. BMJ Case Rep. 2025 Feb 16;18(2)
Dugauquier A, Awada AH, Motulsky E, Kisma N. INTRAVITREAL METHOTREXATE IN VEMURAFENIB-INDUCED UVEITIS. Retin Cases Brief Rep. 2024 Jul 01;18(4):455-458.
Conen K, Mosna-Firlejczyk K, Rochlitz C, Wicki A, Itin P, Arnold AW, Gross M, Zimmermann F, Zippelius A. Vemurafenib-induced radiation recall dermatitis: case report and review of the literature. Dermatology. 2015;230(1):1-4.
Sanagawa A, Takase H. Increased Mitochondrial Superoxide Level Is Partially Associated With Vemurafenib-Induced Renal Tubular Toxicity. Basic Clin Pharmacol Toxicol. 2025 Apr;136(4):e70015.
Wanchoo R, Jhaveri KD, Deray G, Launay-Vacher V. Renal effects of BRAF inhibitors: a systematic review by the Cancer and the Kidney International Network. Clin Kidney J. 2016 Apr;9(2):245-51.
Hwang JP, Feld JJ, Hammond SP, Wang SH, Alston-Johnson DE, Cryer DR, Hershman DL, Loehrer AP, Sabichi AL, Symington BE, Terrault N, Wong ML, Somerfield MR, Artz AS. Hepatitis B Virus Screening and Management for Patients With Cancer Prior to Therapy: ASCO Provisional Clinical Opinion Update. J Clin Oncol. 2020 Nov 01;38(31):3698-3715.
Liu X, Solebo AL, Keane PA, Moore DJ, Denniston AK. Instrument-based tests for measuring anterior chamber cells in uveitis: a systematic review protocol. Syst Rev. 2019 Jan 22;8(1):30.