Une nouvelle Dermatologie -...

Une nouvelle DermatologieUne nouvelle DermatologieToxicité cutanée des thérapies ciblées

Vincent SIBAUD, Dermatologue

Unités de Recherche Clinique et de Phase I

Centre Régional de Lutte contre le Cancer – Toulouse

[email protected] Vendredi 11 avril 2014

thérapies ciblées BEVACIZUMABRITUXIMAB

‐Mab = monoclonal antibodies

RITUXIMABTRASTUZUMABPANITUMUMAB

CETUXIMABCETUXIMABPERTUZUMAB

thérapies ciblées BEVACIZUMABRITUXIMABRITUXIMAB

TRASTUZUMABPANITUMUMAB

CETUXIMAB‐Mab = monoclonal antibodies

‐ximab = anticorps chimérique

CETUXIMABPERTUZUMAB

ximab anticorps chimérique

‐zumab = anticorps humanisé

‐mumab = anticorps humain

‐Momab = anticorps murin

thérapies ciblées

‐Mab = monoclonal antibodies

‐ximab = anticorps chimérique

‐zumab = anticorps humanisé

‐mumab = anticorps humain

‐Momab = anticorps murin

RITUXIMAB (MabThera®)TRASTUZUMAB (Herceptin®)PANITUMUMAB (Vectibix®)PANITUMUMAB (Vectibix®)

CETUXIMAB (Erbitux®)PERTUZUMAB

IPILIMUMAB (Y ®)tu = tumoral (ou ti)

IPILIMUMAB (Yervoy®)BEVACIZUMAB (Avastin®)

‐tuximab = anticorps chimerique p q

‐tuzumab = anticorps humanisé

‐tumumab = anticorps humaintumumab = anticorps humain

thérapies ciblées IMATINIBAFATINIB

‐nib = inhibiteur (tyrosine) kinaseAXITINIB

ERLOTINIBSUNITINIBDASATINIBNILOTINIB

TRAMETINIBTRAMETINIBLAPATINIB

VANDETANIBPAZOPANIBPAZOPANIBSORAFENIBGEFITINIB

REGORAFENIBREGORAFENIB TRAMETINIB

VEMURAFENIBDABRAFENIB

Inhibiteurs récepteurs EGF

Cetuximab (Erbitux®): cancer du colon, ORL

Erlotinib (Tarceva®): cancer du poumon, pancréas

Panitinumab (Vectibix®): cancer du colonPanitinumab (Vectibix®): cancer du colon

Lapatinib (Tyverb®): cancer du sein (HER1+HER2)

Maubec E. Phase II study of cetuximab as first‐line single‐drug therapy in patients with unresectable squamous cell carcinoma ofthe skin. J Clin Oncol 2011; 29: 3419‐26.Caron J. Metastatic basal cell carcinoma: report of two cases treated with cetuximab. Br J Dermatol 2009; 161: 702‐3.

Maubec E. Phase II study of cetuximab as first‐line single‐drug therapy in patients with unresectable squamous cell carcinoma ofthe skin. J Clin Oncol 2011; 29: 3419‐26.Caron J. Metastatic basal cell carcinoma: report of two cases treated with cetuximab. Br J Dermatol 2009; 161: 702‐3.

Lacouture ME. Mechanisms of cutaneous toxicities to EGFR inhibitors. Nat Rev Cancer, 2006.Lacouture ME. Mechanisms of cutaneous toxicities to EGFR inhibitors. Nat Rev Cancer, 2006.

Inhibiteurs récepteurs EGF - anti MEK

Papulopustules and/or paronychia regulatoryPapulopustules and/or paronychia, regulatory abnormalities of hair growth, itching, and dryness due to epidermal growth factor

Lacouture ME The PRIDE syndrome Br J Dermatol 2006Lacouture ME The PRIDE syndrome Br J Dermatol 2006

receptor inhibitors

Lacouture ME. The PRIDE syndrome. Br J Dermatol, 2006. Lacouture ME. The PRIDE syndrome. Br J Dermatol, 2006.

Nb: Trastuzumab (Herceptine®), inhibiteur HER2 – pas de tox cutanée


Éruptions « acnéiformes » (80% des cas)

Robert C. cutaneous side effects of kinase inhibitors and blocking antibodies. Lancet Oncol 2005; 6: 491‐500.Robert C. cutaneous side effects of kinase inhibitors and blocking antibodies. Lancet Oncol 2005; 6: 491‐500.

ÉInhibiteurs récepteurs EGF


Robert C, Sibaud V, Mateus C, Cherpelis BS. Advances in the management of cutaneous toxicities of targeted therapies. Semin Oncol 2012; 39: 227‐240.Robert C, Sibaud V, Mateus C, Cherpelis BS. Advances in the management of cutaneous toxicities of targeted therapies. Semin Oncol 2012; 39: 227‐240.



Segaert S. Clinical signs, pathophysiology and management of skin toxicity during therapy with epidermal growth factor receptor inhibitors. Ann Oncol 2005; 16: 1425‐1433.Segaert S. Clinical signs, pathophysiology and management of skin toxicity during therapy with epidermal growth factor receptor inhibitors. Ann Oncol 2005; 16: 1425‐1433.

Inhibiteurs MEK

Éruption folliculaire papulo-pustuleuse (77-80%)

Infante JR. Safety, pharmacokinetic, pharmacodynamic, and efficacy data for the oral MEK inhibitor trametinib: a phase 1 dose‐l i i l O l 2012 13 3 81

Infante JR. Safety, pharmacokinetic, pharmacodynamic, and efficacy data for the oral MEK inhibitor trametinib: a phase 1 dose‐l i i l O l 2012 13 3 81escalation trial. Lancet Oncol 2012; 13: 773‐81.

Querfeld C. Disseminated follicular eruption during therapy with the MEK inhibitor AZD6244. J Am Acad Dermatol, 2011.Desar IME. Case studies showing clinical signs and management of cutaneous toxicity of the MEK1/2 inhibitor (ARRY‐142886) in patients with solid tumors. Acta Oncol 2010; 110‐3.

escalation trial. Lancet Oncol 2012; 13: 773‐81.Querfeld C. Disseminated follicular eruption during therapy with the MEK inhibitor AZD6244. J Am Acad Dermatol, 2011.Desar IME. Case studies showing clinical signs and management of cutaneous toxicity of the MEK1/2 inhibitor (ARRY‐142886) in patients with solid tumors. Acta Oncol 2010; 110‐3.


Lacouture ME. Skin toxicity evaluation protocol with panitunumab (STEPP), a phase II, open‐label, randomized trial evaluating the impact of a pre‐emptive skin treatment regimen on skin toxicities and quality of life in patients with metastatic colorectal cancer. J Clin Oncol, 2010.

Lacouture ME. Skin toxicity evaluation protocol with panitunumab (STEPP), a phase II, open‐label, randomized trial evaluating the impact of a pre‐emptive skin treatment regimen on skin toxicities and quality of life in patients with metastatic colorectal cancer. J Clin Oncol, 2010.

Que « nous apporte » cette dermatotoxicité?Marqueur de réponse thérapeutique

Petrelli F. The predictive role of skin rash with cetuximab and panitumumab in colorectal cancer patients: a systematic review and meta‐analysis of published trials. Targ Oncol, 2013.Pettrelli F. Relationship between skin rash and outcome in non‐small –cell lung cancer patients treated with anti EGFR tyrosine kinase inhibitors: a literature‐based meta‐analysis of 24 trials. Lung Cancer 2012; 78: 8‐15.

Petrelli F. The predictive role of skin rash with cetuximab and panitumumab in colorectal cancer patients: a systematic review and meta‐analysis of published trials. Targ Oncol, 2013.Pettrelli F. Relationship between skin rash and outcome in non‐small –cell lung cancer patients treated with anti EGFR tyrosine kinase inhibitors: a literature‐based meta‐analysis of 24 trials. Lung Cancer 2012; 78: 8‐15.y g ;y g ;


Xérose cutanée (40%)( )

Heidary N. Chemotherapeutic agents and the skin: an update. J Am Acad Dermatol, 2008. Heidary N. Chemotherapeutic agents and the skin: an update. J Am Acad Dermatol, 2008.

FissuresAppareil peri‐unguéal

Fissures

LacoutureME Clinical practice guidelines for the prevention and treatment of EGFR inhibitor associated dermatologic toxicities Support Care Cancer 2011; 19:LacoutureME Clinical practice guidelines for the prevention and treatment of EGFR inhibitor associated dermatologic toxicities Support Care Cancer 2011; 19:Lacouture ME. Clinical practice guidelines for the prevention and treatment of EGFR inhibitor‐associated dermatologic toxicities. Support Care Cancer 2011; 19: 1079‐1095.Thomas M, Robert C. Dermatologic manifestations of MEK inhibitors. In : Sibaud V, Robert C, eds. Skin side effects induced by targeted anticancer therapies : a new dermatology. Toulouse : Privat, 2010 ; 89‐ 94.

Lacouture ME. Clinical practice guidelines for the prevention and treatment of EGFR inhibitor‐associated dermatologic toxicities. Support Care Cancer 2011; 19: 1079‐1095.Thomas M, Robert C. Dermatologic manifestations of MEK inhibitors. In : Sibaud V, Robert C, eds. Skin side effects induced by targeted anticancer therapies : a new dermatology. Toulouse : Privat, 2010 ; 89‐ 94.

Appareil peri‐unguéal

Paronychies

Inhibiteurs EGFR – MEK – mTOR(afatinib, erlotinib, cetuximab, gefetinib, trametinib, selumetinib, everolimus, temsirolimus….)

Sibaud V and Robert C, Mateus C and Baran R. Nail toxicities induced by systemic anticancer treatments. Lancet Oncol, 2014 (submitted). Sibaud V and Robert C, Mateus C and Baran R. Nail toxicities induced by systemic anticancer treatments. Lancet Oncol, 2014 (submitted).

Appareil peri‐unguéalgranulomes pyogeniques (20%)


Sibaud V, Chevreau C, Mourey L et al. Pyogenic granuloma induced by m TOR inhibitors. Acta Dermatol Venereol 2011; 91: 584‐5.Sibaud V, Chevreau C, Mourey L et al. Pyogenic granuloma induced by m TOR inhibitors. Acta Dermatol Venereol 2011; 91: 584‐5.

Granulomes pyogéniques ‐ prise en charge

Baran R. Nail toxicity of targeted anticancer therapies. In: Cutaneous side effects induced by targeted anticancer therapies: a new dermatology. Sibaud V, Robert C. Editions Privat.Kiyohara Y. Erlotinb‐related skin toxicities : treatment strategies in patients with metastatic non small cell lung cancer. J Am Acad Dermatol, 2013.

Baran R. Nail toxicity of targeted anticancer therapies. In: Cutaneous side effects induced by targeted anticancer therapies: a new dermatology. Sibaud V, Robert C. Editions Privat.Kiyohara Y. Erlotinb‐related skin toxicities : treatment strategies in patients with metastatic non small cell lung cancer. J Am Acad Dermatol, 2013.

Granulomes pyogéniques ‐ prise en chargeGranulomes pyogéniques ‐ prise en charge podologique



Chimiothérapie et tablette unguéale (taxanes, capecitabine, doxorubicine, cisplatine, 5FU…)


Chimiothérapie et tablette unguéale

hyperpigmentationchimiothérapie

hyperpigmentation

Sibaud V, Fricain JC, Baran R, Robert C. Pigmentary disorders induced by anticancer agents. Part I: chemotherapy. Ann Dermatol Venereol 2013; 140: 183‐96.Sibaud V, Fricain JC, Baran R, Robert C. Pigmentary disorders induced by anticancer agents. Part I: chemotherapy. Ann Dermatol Venereol 2013; 140: 183‐96.

Inhibiteurs récepteurs EGF et MEK

Trichomegalie - hypertrichose

Schad K. Mitogen‐activated protein/extracellular signal‐regulated kinase kinase inhibition results in biphasic alteration of epidermal homeostasis with keratinocytic apoptosis and pigmentation disorders Clin Cancer Res 2010; 16: 1058‐64Schad K. Mitogen‐activated protein/extracellular signal‐regulated kinase kinase inhibition results in biphasic alteration of epidermal homeostasis with keratinocytic apoptosis and pigmentation disorders Clin Cancer Res 2010; 16: 1058‐64homeostasis with keratinocytic apoptosis and pigmentation disorders. Clin Cancer Res 2010; 16: 1058‐64.Robert C, Sibaud V, Mateus C, Cherpelis BS. Advances in the management of cutaneous toxicities of targeted therapies. Semin Oncol 2012; 39: 227‐240.

homeostasis with keratinocytic apoptosis and pigmentation disorders. Clin Cancer Res 2010; 16: 1058‐64.Robert C, Sibaud V, Mateus C, Cherpelis BS. Advances in the management of cutaneous toxicities of targeted therapies. Semin Oncol 2012; 39: 227‐240.


Modifications des cheveux

Lynch TJ. Epidermal growth factor receptor inhibitor associated cutaneous toxicities: an evolving paradigm in clinical management. Oncologist, 2007. Agero R. Dermatologic side effects associated with the epidermal growth factor receptors inhibitors. J Am Acad Dermatol, 2006.

Lynch TJ. Epidermal growth factor receptor inhibitor associated cutaneous toxicities: an evolving paradigm in clinical management. Oncologist, 2007. Agero R. Dermatologic side effects associated with the epidermal growth factor receptors inhibitors. J Am Acad Dermatol, 2006.ge o e a o og c s de e ec s assoc a ed e ep de a g o ac o ecep o s b o s cad e a o , 006Osio A. Cutaneous side effects in patients on long term treatment with epidermal growth factor receptor inhibitors. Br J Dermatol, 2009.

ge o e a o og c s de e ec s assoc a ed e ep de a g o ac o ecep o s b o s cad e a o , 006Osio A. Cutaneous side effects in patients on long term treatment with epidermal growth factor receptor inhibitors. Br J Dermatol, 2009.

Alopecie chimiothérapie

Paus R, Haslam I, Sharov AA, Botcharev. Pathobiology of chemotherapy‐induced hair loss. Lancet Oncol 2013; 14:e50‐59.Paus R, Haslam I, Sharov AA, Botcharev. Pathobiology of chemotherapy‐induced hair loss. Lancet Oncol 2013; 14:e50‐59.Tallon B, Blanchard E, Goldberg LJ. Permanent chemotherapy‐induced alopecia: histopathologic criteria still to be defined. J Am Acad Dermatol 2013;68:e151‐2.Tallon B, Blanchard E, Goldberg LJ. Permanent chemotherapy‐induced alopecia: histopathologic criteria still to be defined. J Am Acad Dermatol 2013;68:e151‐2.

Alopecie chimiothérapie

Paus R, Haslam I, Sharov AA, Botcharev. Pathobiology of chemotherapy‐induced hair loss. Lancet Oncol 2013; 14:e50‐59.Tallon B Blanchard E Goldberg LJ Permanent chemotherapy induced alopecia: histopathologic criteria still to be defined J Am Acad Dermatol 2013;68:e151 2Paus R, Haslam I, Sharov AA, Botcharev. Pathobiology of chemotherapy‐induced hair loss. Lancet Oncol 2013; 14:e50‐59.Tallon B Blanchard E Goldberg LJ Permanent chemotherapy induced alopecia: histopathologic criteria still to be defined J Am Acad Dermatol 2013;68:e151 2Tallon B, Blanchard E, Goldberg LJ. Permanent chemotherapy‐induced alopecia: histopathologic criteria still to be defined. J Am Acad Dermatol 2013;68:e151‐2.Tallon B, Blanchard E, Goldberg LJ. Permanent chemotherapy‐induced alopecia: histopathologic criteria still to be defined. J Am Acad Dermatol 2013;68:e151‐2.

Inhibiteurs (B)RAFInhibiteurs (B)RAF

sorafenib (Nexavar®)( )

regorafenib (Stivarga®)

( )Vemurafenib (Zelboraf®)

dabrafenib (Tafinlar®)

Inhibiteur BRAF – VemurafenibKeratoacanthomes – carcinomes épidermoides (18-31%)

8 à 12 semaines- zones photo-exposées ou non – (H)RAS mutations

Sosman JA. Survival in BRAF V600‐mutant advanced melanoma treated with vemurafenib. N Eng J Med 2012; 366: 707‐714.Chapman PB. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 2011; 364: 2507‐2515.Flaherty KT. Inhibition of mutated, activated BRAF in metastatic melanoma.N Engl J Med 2010; 363: 809‐19.

Sosman JA. Survival in BRAF V600‐mutant advanced melanoma treated with vemurafenib. N Eng J Med 2012; 366: 707‐714.Chapman PB. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 2011; 364: 2507‐2515.Flaherty KT. Inhibition of mutated, activated BRAF in metastatic melanoma.N Engl J Med 2010; 363: 809‐19.

Inhibiteur BRAF – Vemurafenib

Lésions hyperkératosiques induites

•hyperkératose du mamelon

• Dyskératose acantholytique (Grover-like)y y q ( )

•Lésions kystiques (épidermiques, miliaires…)

Anforth RM. Cutaneous Manifestations of Dabrafenib (GSK2118436): A Selective Inhibitor of Mutant BRAF in patients with Metastatic Melanoma. Br J Dermatol Anforth RM. Cutaneous Manifestations of Dabrafenib (GSK2118436): A Selective Inhibitor of Mutant BRAF in patients with Metastatic Melanoma. Br J Dermatol 2012; 167: 1153‐60.Boyd KP. Nonmalignant cutaneous findings associated with vemurafenib use in patients with metastatic melanoma. J Am Acad Dermatol 2012; 67: 1375‐9.2012; 167: 1153‐60.Boyd KP. Nonmalignant cutaneous findings associated with vemurafenib use in patients with metastatic melanoma. J Am Acad Dermatol 2012; 67: 1375‐9.

Inhibiteurs BRAF

Lésions kystiques

Chu EY et al. Diverse cutaneous side effects associated with BRAF inhibitor therapy: A clinicopathologic study. J Am Acad Dermatol 2012; 67: 1265‐72.Huang V. Cutaneous toxic effects associated with vemurafenib and inhibition of the BRAF pathway. Arch Dermatol 2012; 148: 628‐33.Chu EY et al. Diverse cutaneous side effects associated with BRAF inhibitor therapy: A clinicopathologic study. J Am Acad Dermatol 2012; 67: 1265‐72.Huang V. Cutaneous toxic effects associated with vemurafenib and inhibition of the BRAF pathway. Arch Dermatol 2012; 148: 628‐33.

Inhibiteur BRAF

Keratose pilaire likeKeratose pilaire-like

Lacouture ME. Analysis of dermatologic events in vemurafenib‐treated patients with melanoma. The Oncologist 2013; 18: 314‐22.Lacouture ME. Analysis of dermatologic events in vemurafenib‐treated patients with melanoma. The Oncologist 2013; 18: 314‐22.

inhibiteur BRAFSyndrome main-pied

Sibaud V, Lamant L, Delord JP. Skin adverse events induced by BRAF inhibitors: a systematic review. Ann Dermatol Venereol 2013; 140: 510‐20.Sibaud V, Lamant L, Delord JP. Skin adverse events induced by BRAF inhibitors: a systematic review. Ann Dermatol Venereol 2013; 140: 510‐20.

Sibaud V et al. HFS 14: a specific quality of life scale for patients suffering from hand‐foot syndrome. The Oncologist 2011; 16: 1469‐78.Sibaud V et al. HFS 14: a specific quality of life scale for patients suffering from hand‐foot syndrome. The Oncologist 2011; 16: 1469‐78.

Syndrome main‐pied et thérapies ciblées (‐nib)

Incidence all grades (%)

Incidence High grades (%)

Cibles indicationsall grades (%) High grades (%)

Regorafenib (Stivarga ®) 60,5 20,4 VEGFR 1‐3; PDGFR α‐β; c‐KIT; RAF;TIE‐2; RET; P38 MAPK, FGFR‐ 1

K colorectal

Sorafenib (Nexavar ®) 33,8 8,9 VEGFR 1‐3; PDGFR β; c‐KIT, RET, RAF

K hépato‐cellulaires et rénaux

Sunitinib (Sutent®) 18,9 5,5 VEGFR 1‐3; PDGFR β; c‐KIT, RET; Flt3; CSF‐1R

K rein et GIST

Axitinib (Inlyta ®) 29,2 9,6 VEGFR 1‐3; PDGFR α‐β; c‐KIT K rein

Vemurafenib (Zelboraf®) 7‐23 2 BRAF Mélanome métastatique et localement avancé

Pazopanib (Votrient®) 4,5 1,8 VEGFR 1‐3; PDGFR α‐β; c‐KIT; RAF

K rein

Balagula Y. The risk of hand foot skin reaction to pazopanib, a novel multikinase inhibitor: a systematic review of literature and meta‐analysis. Invest New Drugs, 2011.Belum VR The risk of hand foot skin reaction with the novel multikinase inhibitor regorafenib: a meta analysis Invest New Drugs 2013

Balagula Y. The risk of hand foot skin reaction to pazopanib, a novel multikinase inhibitor: a systematic review of literature and meta‐analysis. Invest New Drugs, 2011.Belum VR The risk of hand foot skin reaction with the novel multikinase inhibitor regorafenib: a meta analysis Invest New Drugs 2013Belum VR. The risk of hand foot skin reaction with the novel multikinase inhibitor regorafenib: a meta‐analysis. Invest New Drugs, 2013.Fischer A. The risk of hand foot skin reaction to axitinib, a novel VEGF inhibitor: a systematic review of literature and meta‐analysis. Invest New Drugs, 2013.Belum VR. The risk of hand foot skin reaction with the novel multikinase inhibitor regorafenib: a meta‐analysis. Invest New Drugs, 2013.Fischer A. The risk of hand foot skin reaction to axitinib, a novel VEGF inhibitor: a systematic review of literature and meta‐analysis. Invest New Drugs, 2013.

Syndrome main-pied et chimiothérapie(d bi i it bi t FU)(doxorubicine, capecitabine, taxanes, FU)

hyperpigmentationchimiothérapie

hyperpigmentation

Sibaud V, Robert C. pigmentary disorders induced by anticancer agents. Part II: targeted therapies. Ann Dermatol Venereol 2013; 140:266‐73.Sibaud V, Robert C. pigmentary disorders induced by anticancer agents. Part II: targeted therapies. Ann Dermatol Venereol 2013; 140:266‐73.

Syndrome main-pied et chimiothérapie(d bi i li l lé it bi )(doxorubicine liposomale pegylée, capecitabine…..)

Lassere Y. Management of hand‐foot syndrome in patients treated with capecitabine. Eur J oncol Nurs, 2004.Lassere Y. Management of hand‐foot syndrome in patients treated with capecitabine. Eur J oncol Nurs, 2004.Abushullaih S. Incidence and severity of hand‐foot syndrome in colorectal cancer patients treated with capecitabine: a single‐institution experience. Cancer Invest, 2002.Wasif Saif M. Capecitabine and hand‐foot syndrome. Exp Opin Drug Saf 2011; 10: 159‐69.

Abushullaih S. Incidence and severity of hand‐foot syndrome in colorectal cancer patients treated with capecitabine: a single‐institution experience. Cancer Invest, 2002.Wasif Saif M. Capecitabine and hand‐foot syndrome. Exp Opin Drug Saf 2011; 10: 159‐69.

inhibiteur BRAF – Vemurafenib naevi éruptifs

Sibaud V, Fricain JC, Baran R, Robert C. Pigmentary disorders induced by anticancer agents. Part I: chemotherapy. Ann Dermatol Venereol 2013; 140: 183‐96.Sibaud V, Fricain JC, Baran R, Robert C. Pigmentary disorders induced by anticancer agents. Part I: chemotherapy. Ann Dermatol Venereol 2013; 140: 183‐96.

Sorafenib – vemurafenib -dabrafenib

naevi éruptifs

RAF inhibition

Kong HH, Sibaud V, Chevreau C. Sorafenib‐induced eruptive melanocytic lesions. Arch Dermatol 2008; 144: 820‐2. Munsch C, Lamant L, Sibaud V. Eruptive nevi with regorafenib: the first report of an ancient adverse event !. Clin Colorectal Cancer (submitted).

Kong HH, Sibaud V, Chevreau C. Sorafenib‐induced eruptive melanocytic lesions. Arch Dermatol 2008; 144: 820‐2. Munsch C, Lamant L, Sibaud V. Eruptive nevi with regorafenib: the first report of an ancient adverse event !. Clin Colorectal Cancer (submitted).

Naevi induitsCapecitabine

Naevi induits

Sibaud V, Robert C. pigmentary disorders induced by anticancer agents. Part II: targeted therapies. Ann Dermatol Venereol 2013; 140:266‐73.Sibaud V, Robert C. pigmentary disorders induced by anticancer agents. Part II: targeted therapies. Ann Dermatol Venereol 2013; 140:266‐73.

inhibiteur BRAF – Vemurafenib

naevi éruptifs (10%) Mélanomes de novonaevi éruptifs (10%) – Mélanomes de novo

Haenssle HA et al. Dynamic Changes in Nevi of a Patient With Melanoma Treated With Vemurafenib: Importance of Sequential Dermoscopy. Arch Dermatol 2012; 20:1‐3. Zimmer L et al Atypical melanocytic proliferations and new primary melanomas in patients with advanced melanoma undergoing

Haenssle HA et al. Dynamic Changes in Nevi of a Patient With Melanoma Treated With Vemurafenib: Importance of Sequential Dermoscopy. Arch Dermatol 2012; 20:1‐3. Zimmer L et al Atypical melanocytic proliferations and new primary melanomas in patients with advanced melanoma undergoingZimmer L et al. Atypical melanocytic proliferations and new primary melanomas in patients with advanced melanoma undergoing selective BRAF inhibition. J Clin Oncol 2012;30:2375‐83.Zimmer L et al. Atypical melanocytic proliferations and new primary melanomas in patients with advanced melanoma undergoing selective BRAF inhibition. J Clin Oncol 2012;30:2375‐83.

inhibiteur BRAF

Alopéciep

Sibaud V, Lamant L, Delord JP. Skin adverse events induced by BRAF inhibitors: a systematic review. Ann Dermatol Venereol 2013; 140: 510‐20.Sibaud V, Lamant L, Delord JP. Skin adverse events induced by BRAF inhibitors: a systematic review. Ann Dermatol Venereol 2013; 140: 510‐20.

Toxicité buccale –ulcérations aphtoidestrametinib sunitinibcetuximab

everolimuseverolimus temsirolimus

Sibaud V, Fricain JC. Oral manifestations induced by new targeted anticancer therapies. Ann Dermatol Venereol, 2013 (submitted).Sibaud V, Fricain JC. Oral manifestations induced by new targeted anticancer therapies. Ann Dermatol Venereol, 2013 (submitted).

Langue géographique et antiangiogéniques (sorafenib, sunitinib, bevacizumab)

Hubiche T, Valenza B, Chevreau C, Fricain JC, Del Giudice P, Sibaud V. Geographic tongue induced by angiogenesis inhibitors. Oncologist 2013; 18: e16‐7.Hubiche T, Valenza B, Chevreau C, Fricain JC, Del Giudice P, Sibaud V. Geographic tongue induced by angiogenesis inhibitors. Oncologist 2013; 18: e16‐7.

Hyperkétatose et inhibiteurs BRAF (vemurafenib)BRAF (vemurafenib)

Boussemart L,et al. Prospective study of cutaneous side‐effects associated with the BRAF inhibitor vemurafenib: a study of 42 patients. Ann Oncol 2013;24:1691‐7. Boussemart L,et al. Prospective study of cutaneous side‐effects associated with the BRAF inhibitor vemurafenib: a study of 42 patients. Ann Oncol 2013;24:1691‐7.

E thèEn synthèse

• P d’ ff t i dé i bl lité d i t t è• Peu d’effets indésirables « graves »; qualité de vie souvent très altérée

•Approche multidisciplinaire

•Rôle fondamental du dermatologue

• Nouveaux effets indésirables à « découvrir » +++

• « Rôle de la peau » comme marqueur tumoral?

Balagula Y. The emergence of supportive oncodermatology: the study of dermatologic adverse events to cancer therapies. J Am Acad Dermatol 2011; 65: 624‐35. Balagula Y. The emergence of supportive oncodermatology: the study of dermatologic adverse events to cancer therapies. J Am Acad Dermatol 2011; 65: 624‐35.

Balagula Y. The emergence of supportive oncodermatology: the study of dermatologic adverse events to cancer therapies. J Am Acad Dermatol 2011; 65: 624‐35Balagula Y. The emergence of supportive oncodermatology: the study of dermatologic adverse events to cancer therapies. J Am Acad Dermatol 2011; 65: 624‐35Dermatol 2011; 65: 624‐35. Dermatol 2011; 65: 624‐35.

Une nouvelle Dermatologie -...

Documents

Transcript of Une nouvelle Dermatologie -...