Dermatologists & Oncologists: Two important reasons we are getting closer. Ioanna Panoutsopoulou, MD. GAMC June 1 st 2016

Transcription

1 Dermatologists & Oncologists: Two important reasons we are getting closer Ioanna Panoutsopoulou, MD GAMC June 1 st 2016

2 Points of presentation Cutaneous adverse events from: Epidermal Growth Factor Receptor Inhibitors (EGFRi) Melanoma Treatments

3 Targeted oncologic treatments Side effects on skin, hair and nails are common affect quality of life May lead to antineoplastic treatment discontinuation Dermatologist s role is important in managing the cancer patients Average cost of managing the skin toxicities: $1920 per pt/year Borovicka JH et al. Arch Dermatol. 2011;147:

4 Epidermal Growth Factor Receptor Inhibitors (EGFR inhibitors) Monoclonal antibodies to EGFR: cetuximab, panitumumab Tyrosine Kinase inhibitors specific for EGFR: erlotinib, gefitinib Dual kinase inhibitors of EGFR and HER2: lapatinib Inhibitors of erbb receptors: canertinib Multikinase inhibitors: vandetanib

5 EGFR inhibitors Why so many cutaneous side effects? EGFR: Located in epidermis and appendages 1 Important in homeostasis of epidermis and pilosebaceous unit2, 3, 4 Inhibits IL-5 perifollicular inflammation 5 Affects IL Green MR et al. J Invest Dermatol. 1985;85: Lacouture ME. Nat Rev Cancer. 2006;6: Murillas R et al. EMBO J. 1995;14: Brodell LA et al. J Cutan Pathol. 2013;40: Rodeck U. J Cell Physiol. 2009;218: Bangsgaard N. PLoS One. 2012;7:e39706

6 50-90% of the pts receiving EGFRi will develop cutaneous side effects

7 EGFRi Papulopustular lesions Most common side effect Aseptic folliculitus Rapid onset: 75% of pts within 1-2 wks 1,2 Dose-dependent Milia are absent Associated pruritus Distribution: head, neck, trunk, proximal aspect of extremities Pustules may lead to: Crusted or hyperkeratotic papules Bacterial infection 1. Cunningham D et al. N Engl J Med. 2004;351: Lacouture ME et al. Support Care Cancer. 2011;19:

8 Panitumumab 61 yo colon Ca

9 9/3/15 9/3/15 30/3/15 11/5/15

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11 s/p 2 wks doxycycline 100 mg BID + Methylprednisolone aceponate lot bid Panitumumab colon Ca while on same dose of panitumumab

12 Panitumumab colon Ca s/p 2 wks doxycycline 100 mg BID + Methylprednisolone aceponate lot bid while on same dose of panitumumab

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14 Panitumumab (EGFRi) 43 yo F colon Ca

15 panitumumab (EGFRi) 60 yo M colon Ca Erlotinib (EGFRi) 81 yo M renal Ca

16 EGFR inhibitors Papulopustular lesions Flares when 1 : EGFRi dose EGFRi held and re-introduced Exposure to UV worsening 2 Irradiated areas not involved 3 Degree of lesion severity associated with: Creatinic kinase levels (CK) Maybe better prognosis 4,5 1. Segart S et al. Ann Oncol. 2005;16: Luu M et al. Photodermatol Photoimmunol Photomed. 2007;23: Bossi P et al. Ann Oncol. 2007;18: Perez-Soler R. Oncology. 2003;17(11 Suppl 12): Liu HB et al. PlosOne. 2013;8:e55128

17 EGFR inhibitors Papulopustular lesions Grading of severity: body surface area (BSA) affected Activities of daily living (ADL)

18 EGFR inhibitors Side effects Photosensivity photodermatitis telangiectasias xerosis 30% of pts Dose-dependent Skin fragility cracks Necitumumab + capecitabine

19 photosensitivity

20 2/2/15 26/2/15 Necitumumab + capecitabine Lung cancer

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22 EGFR inhibitors Secondary skin infections Staph aureus Pseudomonas aeruginosa Herpes simples

23 Panitumumab 83 yo colon Ca Staph aureus

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25 Pseudomonas aeruginosa infection Panitumumab colon Ca s/p amikacin gel BID

26 EGFRi & Hair Hair quality changes: after 2 nd 3 rd month 1. Scalp hair: thinner, fragile, curlier 1 hair growth rate Mild androgenetic alopecia Case reports: scarring alopecia by erlotinib, loss of pigment 2. Facial hair: Eyelashes: trichomegaly (elongated, thicker, curly 2,3 ) keratitis eyebrows: hypertrichosis, in-between the eyebrows and periorbital area 4 Hypertrichosis: upper lip and chin 1. Zheng et al. BMJ Case Rep. Published online 2009 Mar Criado PR et al. An Bras Dermatol. 2010;85: Rodriguez NA et al. J Clin Oncol. 2011;29:e532-e Pascual JC et al. Br J Dermatol. 2004;151:

27 Panitumumab (EGFRi) 43 yo F colon Ca

28 Panitumumab (EGFRi) 43 yo F colon Ca 6 months later while on panitumumab

29 Panitumumab (EGFRi) 43 yo F colon Ca

30 Panitumumab colon Ca

31 Afatinib lung Ca

32 EGFRi & mucosa Oral mucosa: Aphthae, dry mouth, geographic tongue Genital mucosa: Valanitis, vaginitis, aphthae eyes: Conjuctivitis & keratitis 1. Busam KJ et al. Br J Dermatol. 2001;144: Melichar B et al. Eur J Cancer Care. 2007;16:

33 EGFRi & nails 20% of pts 1 Paronychia Pyogenic granuloma like lesions Nail dyschromias onycholysis 1. Garden BC et al. J Am Acad Dermatol. 2012;67: Fox LP. J Am Acad Dermatol. 2007;

34 Erlotinib (EGFRi) Necitumumab + capecitabine Panitumumab (EGFRi) Cetuximab (EGFRi)

35 PG-like lesions Afatinib 22 y.o. lung Ca

36 Melanoma Treatments RAF inhibitors: vemurafenib, dabrafenib MEK inhibitors: trametinib, cobimetinib, selumetinib Immunomodulators: Anti-CTLA-4 : ipilimumab (tremelimumab) Anti-PD-1 inhibitors: nivolumab, pebrolizumab, (pidilizumab)

37 RAF inhibitors Folliculocentric smooth papules: 70% of pts extensive maculo-papular eruption plaques Location: trunk & extremities: (spares head/neck) vemurafenib

38 RAF inhibitors - Cutaneous neoplams SCCs (RAS mutation) 1 & Keratoacanthomas 1. Su F et al. N Enlg J Med. 2012;366:

39 Vemurafenib - Ακανθοκυτταρικά καρκινώματα

40 RAF inhibitors - Cutaneous neoplams verruca keratoses 1 Photo- exposed and non photo-exposed areas Minimal to no atypia HPV negative 1. Anforth RM et al. Br J Dermatol. 2012;167:

41 Vemurafenib 48 yo M melanoma verrucous keratoses

42 Dabrafenib 72 yo F melanoma

43 RAF inhibitors Palmo-plantar hyperkeratosis 1,2 60% of pts Friction Prevention: avoiding friction and pressure on skin 1. Huang V et al. Arch Dermatol. 2012;148: Anforth RM et al. Br J Dermatol. 2012;167:

44 Dabrafenib + trametinib 33 yo M melanoma Vemurafenib 48 yo M melanoma

45 RAF inhibitors Follicular keratosis 1 30% of pts pruritus Seborrheic dermatitis 2 pruritus 1. Harvey NT et al. Am J Dermatopathol. 2012;34: Huang V et al. Arch Dermatol. 2012;148:

46 RAF inhibitors - Photosensitivity vemurafenib > dabrafenib Sun burns Urticarial lesions Pain Sinha R et al. Br J Dermatol. 2012;167: Dummer R et al. N Engl J Med. 2012;366:

47 RAF inhibitors Non scarring alopecia Facial erythema Eruptive milia Epidermal cysts Radiation recall dermatitis Lobular panniculitis 1,2 (neutrophilic) Upper & lower extremities Arthralgia vemurafenib 1. Bussemart L et al. Ann Oncol. 2013;24: Kim GH et al. J Cutan Pathol. 2013;40:

48 Vemurafenib 35 yo F melanoma eruptive milia

49 RAF inhibitors & pigmented lesions Change of existing nevi 1 New nevi 1,2 Second primary melanoma 3,4 1. Haenssle HA et al. Arch Dermatol. 2012;148: Boussemart L et al. Ann Oncol. 2013;24: Dalle S et al. Br J Dermatol. 2013;168: Debarbieux S et al. Br J Dermatol. 2013;168:

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51 MEK inhibitors trametinib, cobimetinib, selumetinib Side effects similar to EGFRi Combined therapy of MEK & RAF inhibitors fewer side effects 1. Adjei AA et al. J Clin Oncol. 2008;26: Davies BR et al. Mol Cancer Ther. 2007;6: Gadiot J et al. Onco Targets Ther. 2013;6:

52 MEK inhibitors Side Effects Maculopapular erythematous lesions 50-75% of pts 1 Dose-dependent 1,2 Papulopustular lesions 3 Head/neck/trunk pruritus infection with Staphylococcus aureus 1. Banerji U et al. Clin Cancer Res. 2010;16: Adjei AA et al. J Clin Oncol. 2008;26: Balagula Y et al. Invest New Drugs. 2011;29:

53 MEK inhibitors Xerosis - pruritus Alopecia (17% of pts) Skin hyperpigmentation Trichomegaly, hair de-pigmentation paronychia telangiectasias 1. Banerji U et al. Clin Cancer Res. 2010;16: Adjei AA et al. J Clin Oncol. 2008;26: Balagula Y et al. Invest New Drugs. 2011;29:

54 Dose-dependent Anti-CTLA-4 (Ipilimumab) side effects Maculopapular Alopecia pruritus vitiligo: maybe better prognosis 1 1. Cancer Biol Ther. 2015;16(5):662-70

55 Anti-PD-1 Nivolumab & Pebrolizumab Cutaneous side effects Pruritus Vitiligo JAMA Dermatol. 2016;152(1):45-51

56 Conclusions Numerous and frequent side effects from targeted antineoplastic treatments Important to diagnose and manage cutaneous side effects: Improve pts quality of life Not decrease the dose of antineoplastic tx Not discontinue the antineoplastic tx

57 Thank you!