Cutaneous toxicities of BRAF inhibitors: Clinical and pathological challenges and call to action

Critical Reviews in Oncology/Hematology

Volumn 88, Issue 2, 2013, Pages 318-337

  Mandalà, Mario ^a   Massi, Daniela ^b   De Giorgi, Vincenzo ^b  

^a PAPA GIOVANNI XXIII HOSPITAL   (Italy)

^b UNIVERSITY OF FLORENCE   (Italy)

Author keywords

BRAF inhibitors; Clinical; Histopathology; Management; Melanoma; Skin toxicity

Indexed keywords

ANALGESIC AGENT; ANTIHISTAMINIC AGENT; B RAF KINASE INHIBITOR; BLEOMYCIN; CAPSAICIN; CARBOPLATIN; CLOBETASOL PROPIONATE; DABRAFENIB; DACARBAZINE; EMLA; IMIQUIMOD; MINOXIDIL; PACLITAXEL; PODOPHYLLOTOXIN; PREDNISOLONE; PREDNISONE; SALICYLIC ACID; SORAFENIB; TRAMETINIB; UREA; VEMURAFENIB;

ACTINIC KERATOSIS; ALOPECIA; BASAL CELL CARCINOMA; CLINICAL FEATURE; CLINICAL TRIAL (TOPIC); DAILY LIFE ACTIVITY; DISEASE ASSOCIATION; DOSE TIME EFFECT RELATION; DRUG CLASSIFICATION; DRUG SAFETY; ERYTHEMA; FOLLICULITIS; FOLLICULITIS PERFORANS; HAIR DISEASE; HAND FOOT SKIN REACTION; HAND FOOT SYNDROME; HISTOPATHOLOGY; HUMAN; HYPERKERATOSIS; KERATOACANTHOMA; KERATOSIS; KIDNEY CARCINOMA; LIVER CELL CARCINOMA; MACULOPAPULAR RASH; MELANOMA; MYCOSIS FUNGOIDES; NONHUMAN; PALMOPLANTAR KERATODERMA; PANNICULITIS; PATIENT MONITORING; PHASE 3 CLINICAL TRIAL (TOPIC); PHOTOSENSITIVITY; PRURITUS; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL (TOPIC); RASH; REVIEW; SEBORRHEIC KERATOSIS; SKIN CARCINOMA; SKIN DEFECT; SKIN DISEASE; SKIN PAPILLOMA; SKIN SURGERY; SKIN TOXICITY; SOLID TUMOR; SQUAMOPROLIFERATIVE LESION; SQUAMOUS CELL CARCINOMA; STEVENS JOHNSON SYNDROME; VERRUCA VULGARIS; VERRUCOUS KERATOSIS;

BRAF INHIBITORS; CLINICAL; HISTOPATHOLOGY; MANAGEMENT; MELANOMA; SKIN TOXICITY;

ANTINEOPLASTIC AGENTS; CARCINOMA, SQUAMOUS CELL; HUMANS; MELANOMA; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS B-RAF; RESEARCH; SKIN; SKIN DISEASES;

EID: 84885838388     PISSN: 10408428     EISSN: 18790461     Source Type: Journal    
DOI: 10.1016/j.critrevonc.2013.06.002     Document Type: Review

References (71)

1. Korn E.L., Liu P.Y., Lee S.J., et al. Meta-analysis of phase II cooperative group trials in metastatic stage IV melanoma to determine progression-free and overall survival benchmarks for future phase II trials. Journal of Clinical Oncology 2008, 26:527-534.
2. Neuman H.B., Patel A., Ishill N., et al. A single-institution validation of the AJCC staging system for stage IV melanoma. Annals of Surgical Oncology 2008, 15:2034-2041.
3. Flaherty K.T., Puzanov I., Kim K.B., et al. Inhibition of mutated, activated BRAF in metastatic melanoma. New England Journal of Medicine 2010, 363:809-819.
4. Davies H., Bignell G.R., Cox C., et al. Mutations of the BRAF gene in human cancer. Nature 2002, 417:949-954.
5. Curtin J.A., Fridlyand J., Kageshita T., et al. Distinct sets of genetic alterations in melanoma. New England Journal of Medicine 2005, 353:2135-2147.
6. Schoenewolf N.L., Bull C., Belloni B., et al. Sinonasal, genital and acrolentiginous melanomas show distinct characteristics of KIT expression and mutations. European Journal of Cancer 2012, 48:1842-1852.
7. Sullivan R.J., Flaherty K. MAP kinase signaling and inhibition in melanoma. Oncogene 2013, 32:2373-2379.
8. Flaherty K.T., Hodi F.S., Fisher D.E. From genes to drugs: targeted strategies for melanoma. Nature Reviews Cancer 2012, 12:349-361.
9. Hauschild A., Grob J.J., Demidov L.V., et al. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet 2012, 380:358-365.
10. Chapman P.B., Hauschild A., Robert C., et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. New England Journal of Medicine 2011, 364:2507-2516.
11. Sosman J.A., Kim K.B., Schuchter L., et al. Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib. New England Journal of Medicine 2012, 366:707-714.
12. Qiao J., Fang H. Hand-foot syndrome related to chemotherapy. Canadian Medical Association Journal 2012, 184:E818.
13. Rinderknecht J.D., Goldinger S.M., Rozati S., et al. RASopathic skin eruptions during vemurafenib therapy. PLoS ONE 2013, 8:e58721.
14. Arnault J.P., Wechsler J., Escudier B., et al. Keratoacanthomas and squamous cell carcinomas in patients receiving sorafenib. Journal of Clinical Oncology 2009, 27:59-61.
15. Autier J., Escudier B., Wechsler J., Spatz A., Robert C. Prospective study of the cutaneous adverse effects of sorafenib, a novel multikinase inhibitor. Archives of Dermatology 2008, 144:886-892.
16. Hong D.S., Reddy S.B., Prieto V.G., et al. Multiple squamous cell carcinomas of the skin after therapy with sorafenib combined with tipifarnib. Archives of Dermatology 2008, 144:779-782.
17. Dubauskas Z., Kunishige J., Prieto V.G., Jonasch E., Hwu P., Tannir N.M. Cutaneous squamous cell carcinoma and inflammation of actinic keratoses associated with sorafenib. Clinical Genitourinary Cancer 2009, 7:20-23.
18. Kong H.H., Cowen E.W., Azad N.S., Dahut W., Gutierrez M., Turner M.L. Keratoacanthomas associated with sorafenib therapy. Journal of the American Academy of Dermatology 2007, 56:171-172.
19. Escudier B., Eisen T., Stadler W.M., et al. Sorafenib in advanced clear-cell renal-cell carcinoma. New England Journal of Medicine 2007, 356:125-134.
20. Llovet J.M., Ricci S., Mazzaferro V., et al. Sorafenib in advanced hepatocellular carcinoma. New England Journal of Medicine 2008, 359:378-390.
21. Hutson T.E., Bellmunt J., Porta C., et al. Long-term safety of sorafenib in advanced renal cell carcinoma: follow-up of patients from phase III TARGET. European Journal of Cancer 2010, 46:2432-2440.
22. Ratain M.J., Eisen T., Stadler W.M., et al. Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma. Journal of Clinical Oncology 2006, 24:2505-2512.
23. Flaherty K.T., Lee S.J., Zhao F., et al. Phase III trial of carboplatin and paclitaxel with or without sorafenib in metastatic melanoma. Journal of Clinical Oncology 2013, 31:373-379.
24. Hauschild A., Agarwala S.S., Trefzer U., et al. Results of a phase III, randomized, placebo-controlled study of sorafenib in combination with carboplatin and paclitaxel as second-line treatment in patients with unresectable stage III or stage IV melanoma. Journal of Clinical Oncology 2009, 27:2823-2830.
25. McDermott D.F., Sosman J.A., Gonzalez R., et al. Double-blind randomized phase II study of the combination of sorafenib and dacarbazine in patients with advanced melanoma: a report from the 11715 Study Group. Journal of Clinical Oncology 2008, 26:2178-2185.
26. Flaherty K.T., Robert C., Hersey P., et al. Improved survival with MEK inhibition in BRAF-mutated melanoma. New England Journal of Medicine 2012, 367:107-114.
27. Anforth R.M., Blumetti T.C., Kefford R.F., et al. Cutaneous manifestations of dabrafenib (GSK2118436): a selective inhibitor of mutant BRAF in patients with metastatic melanoma. British Journal of Dermatology 2012, 167:1153-1160.
28. Sinha R., Edmonds K., Newton-Bishop J.A., Gore M.E., Larkin J., Fearfield L Cutaneous adverse events associated with vemurafenib in patients with metastatic melanoma: practical advice on diagnosis, prevention and management of the main treatment-related skin toxicities. British Journal of Dermatology 2012, 167:987-994.
29. Dummer R., Rinderknecht J., Goldinger S.M. Ultraviolet A and photosensitivity during vemurafenib therapy. New England Journal of Medicine 2012, 366:480-481.
30. Gelot P., Dutartre H., Khammari A., et al. Vemurafenib: an unusual UVA-induced photosensitivity. Experimental Dermatology 2013, 22:297-298.
31. Zimmer L., Livingstone E., Hillen U., Dömkes S., Becker A., Schadendorf D. Panniculitis with arthralgia in patients with melanoma treated with selective BRAF inhibitors and its management. Archives of Dermatology 2012, 148:357-361.
32. Monfort J.B., Pagès C., Schneider P., et al. Vemurafenib-induced neutrophilic panniculitis. Melanoma Research 2012, 22:399-401.
33. Mattei P.L., Alora-Palli M.B., Kraft S., Lawrence D.P., Flaherty K.T., Kimball A.B. Cutaneous effects of BRAF inhibitor therapy: a case series. Annals of Oncology 2013, 24:530-537.
34. Belum V.R., Fischer A., Choi J.N., Lacouture M.E. Dermatological adverse events from BRAF inhibitors: a growing problem. Current Oncology Reports 2013, (March). [Epub ahead of print].
35. Dalle S., Poulalhon N., Debarbieux S., Thomas L. Second primary melanomas on treatment with vemurafenib. British Journal of Dermatology 2013, 168:887-888.
36. Dalle S., Poulalhon N., Thomas L. Vemurafenib in melanoma with BRAF V600E mutation. New England Journal of Medicine 2011, 365:1448-1449.
37. Zimmer L., Hillen U., Livingstone E., et al. Atypical melanocytic proliferations and new primary melanomas in patients with advanced melanoma undergoing selective BRAF inhibition. Journal of Clinical Oncology 2012, 30:2375-2383.
38. Cribier B., Asch P., Grosshans E. Differentiating squamous cell carcinoma from keratoacanthoma using histopathological criteria. Is it possible? A study of 296 cases. Dermatology 1999, 199:208-212.
39. Mandrell J.C., Santa Cruz D. Keratoacanthoma: hyperplasia, benign neoplasm, or a type of squamous cell carcinoma?. Seminars in Diagnostic Pathology 2009, 26:150-163.
40. Hurt M.A. Keratoacanthoma vs. quamous cell carcinoma in contrast with keratoacanthoma is squamous cell carcinoma. Journal of Cutaneous Pathology 2004, 31:291-292.
41. Weedon D. Weedon's skin pathology 2009, Churchill Livingstone, Elsevier, London, UK. 3rd ed.
42. Harvey N.T., Millward M., Wood B.A. Squamoproliferative lesions arising in the setting of BRAF inhibition. American Journal of Dermatopathology 2012, 34:822-826.
43. Manousaridis I., Mavridou S., Goerdt S., Leverkus M., Utikal J. Cutaneous side effects of inhibitors of the RAS/RAF/MEK/ERK signaling pathway and their management. Journal of the European Academy of Dermatology and Venereology 2013, 27:11-18.
44. Anforth R., Fernandez-Peñas P., Long G.V. Cutaneous toxicities of RAF inhibitors. Lancet Oncology 2013, 14:11-18.
45. Chu E.Y., Wanat K.A., Miller C.J., et al. Diverse cutaneous side effects associated with BRAF inhibitor therapy: a clinicopathologic study. Journal of the American Academy of Dermatology 2012, 67:1265-1272.
46. Alloo A., Garibyan L., LeBoeuf N., et al. Photodynamic therapy for multiple eruptive keratoacanthomas associated with vemurafenib treatment for metastatic melanoma. Archives of Dermatology 2012, 148:363-366.
47. Le Boit P.E., Burg G., Weedon D., Sarasin A. World Health Organization Classification of Tumours. Pathology & Genetics of Skin Tumors. II Series 2006, IARC Press, Lyon, France.
48. Weedon D., Malo J., Brooks D., Williamson R. Keratoacanthoma: is it really a variant of squamous cell carcinoma?. ANZ Journal of Surgery 2010, 80:129-130.
49. Kossard S., Tan K.B., Choy C. Keratoacanthoma and infundibulocystic squamous cell carcinoma. American Journal of Dermatopathology 2008, 30:127-134.
50. Diaz-Cascajo C., Borghi S., Weyers W., Bastida-Inarrea J. Follicular squamous cell carcinoma of the skin: a poorly recognized neoplasm arising from the wall of hair follicles. Journal of Cutaneous Pathology 2004, 31:19-25.
51. Arnault J.P., Mateus C., Escudier B., et al. Skin tumors induced by sorafenib; paradoxic RAS-RAF pathway activation and oncogenic mutations of HRAS, TP53, and TGFBR1. Clinical Cancer Research 2012, 18:263-272.
52. Boussemart L., Routier E., Mateus C., et al. Prospective study of cutaneous side-effects associated with the BRAF inhibitor vemurafenib: a study of 42 patients. Annals of Oncology 2013, (February). [Epub ahead of print].
53. Rauen K.A. HRAS and the Costello syndrome. Clinical Genetics 2007, 71:101-108.
54. Siegel D.H., Mann J.A., Krol A.L., Rauen K.A. Dermatological phenotype in Costello syndrome: consequences of Ras dysregulation in development. British Journal of Dermatology 2012, 166:601-607.
55. Siegel D.H., McKenzie J., Frieden I.J., Rauen K.A. Dermatological findings in 61 mutation-positive individuals with cardiofaciocutaneous syndrome. British Journal of Dermatology 2011, 164:521-529.
56. Lacouture M.E., O'Reilly K., Rosen N., Solit D.B. Induction of cutaneous squamous cell carcinomas by RAF inhibitors: cause for concern?. Journal of Clinical Oncology 2012, 30:329-330.
57. Oberholzer P.A., Kee D., Dziunycz P., et al. RAS mutations are associated with the development of cutaneous squamous cell tumors in patients treated with RAF inhibitors. Journal of Clinical Oncology 2012, 30:316-321.
58. Su F., Viros A., Milagre C., et al. RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors. New England Journal of Medicine 2012, 366:207-215.
59. Anforth R., Tembe V., Blumetti T., Fernandez-Peñas P Mutational analysis of cutaneous squamous cell carcinomas and verrucal keratosis in patients taking BRAF inhibitors. Pigment Cell & Melanoma Research 2012, 25:569-572.
60. Yuspa S.H. The pathogenesis of squamous cell cancer: lessons learned from studies of skin carcinogenesis - thirty-third G.H.A. Clowes Memorial Award Lecture. Cancer Research 1994, 54:1178-1189.
61. Quintanilla M., Brown K., Ramsden M., Balmain A. Carcinogen-specific mutation and amplification of Ha-ras during mouse skin carcinogenesis. Nature 1986, 322:78-80.
62. Bizub D., Wood A.W., Skalka A.M. Mutagenesis of the Ha-ras oncogene in mouse skin tumors induced by polycyclic aromatic hydrocarbons. Proceedings of the National Academy of Sciences of the United States of America 1986, 83:6048-6052.
63. Brown K., Buchmann A., Balmain A. Carcinogen-induced mutations in the mouse c-Ha-ras gene provide evidence of multiple pathways for tumor progression. Proceedings of the National Academy of Sciences of the United States of America 1990, 87:538-542.
64. Khan S.G., Mohan R.R., Katiyar S.K., et al. Mutations in ras oncogenes: rare events in ultraviolet B radiation-induced mouse skin tumorigenesis. Molecular Carcinogenesis 1996, 15:96-103.
65. Ratushny V., Gober M.D., Hick R., Ridky T.W., Seykora J.T. From keratinocyte to cancer: the pathogenesis and modeling of cutaneous squamous cell carcinoma. Journal of Clinical Investigation 2012, 122:464-472.
66. Heidorn S.J., Milagre C., Whittaker S., et al. Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF. Cell 2010, 140:209-221.
67. Hatzivassiliou G., Song K., Yen I., et al. RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth. Nature 2010, 464:431-435.
68. Balmain A., Ramsden M., Bowden G.T., Smith J. Activation of the mouse cellular Harvey-ras gene in chemically induced benign skin papillomas. Nature 1984, 307:658-660.
69. Uribe P., Gonzalez S. Epidermal growth factor receptor (EGFR) and squamous cell carcinoma of the skin: molecular bases for EGFR-targeted therapy. Pathology - Research and Practice 2011, 207:337-344.
70. Callahan M.K., Rampal R., Harding J.J., et al. Progression of RAS-mutant leukemia during RAF inhibitor treatment. New England Journal of Medicine 2012, 367:2316-2321.
71. Flaherty K.T., Infante J.R., Daud A., et al. Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. New England Journal of Medicine 2012, 367:1694-1703.