Significance. Outline and Objectives. S007 Systemic Therapies for Medical Oncology

Transcription

1 S007 Systemic Therapies for Medical Oncology Anisha B. Patel, M.D. Assistant Professor, Dermatology UT MD Anderson Cancer Center UT Health Science Center Houston Safety considerations Outline and Objectives Treating cutaneous disease in cancer patients When the cutaneous disease is the cancer Managing cutaneous adverse events/paraneoplastic disease in cancer patients Quality of Life Pain Pruritus Emotional/social impact Activities of daily living Significance 1

2 Cutaneous history Genetic history Oncology history Current medications Safety First! Safety First! Cutaneous history Genetic history Oncology history Current medications Inflammatory skin disease NMSC Melanoma Safety First! Cutaneous history Genetic history Oncology history Current medications P53 BRCA2 Muir Torre/Lynch syndrome 2

3 Safety First! Cutaneous history Genetic history Oncology history Current medications Primary malignancy Myelodysplastic syndrome CLL/SLL Stem cell transplant Metastases Hepatic Renal Recent therapies Bone marrow suppression Risk of hemolysis Question Which of the following are teratogens? A. Isotretinoin B. Vismodegib C. Acitretin D. Sonidegib E. All of the above Safety First! Carcinogenic drugs Solid tumor Cyclosporine Azathioprine Liquid tumor TNF inhibitors Tacrolimus Reproductive considerations Retinoids Vismodegib Sonidegib Everyone is immunosuppressed!! 3

4 Treating Cutaneous Disease in the Cancer Patient Psoriasis Secukinumab Ixekizumab TNF blockers Treating Cutaneous Disease in the Cancer Patient Psoriasis Secukinumab Ixekizumab TNF blockers Acitretin mg daily Screening labs: pregnancy test, fasting lipids CBC w/diff, CMP Monitoring: CBC, LFTs monthy x 3 6 months Followed by Q3 months Treating Cutaneous Disease in the Cancer Patient Psoriasis Secukinumab Ixekizumab TNF blockers Methotrexate mg/wk Folic acid 1 2 mg/day Screening labs: Hep B, Hep C, TB, CBC w/diff, CMP Monitoring: CBC, 1 week Followed by Q 1 2 weeks Followed by Q3 4 months if dose stable Liver biopsy 4

5 Treating Cutaneous Disease in the Cancer Patient Psoriasis Secukinumab Ixekizumab TNF blockers Secukinumab SubQ: 300 mg once weekly x 5 doses, followed by 300 mg Q4 weeks Screening labs: TB, Hep B, Hep C, CBC, CMP Monitoring labs: CBC and CMP Q 3 months No increased risk of leukemia/lymphoma or NMSC (so far) Treating Cutaneous Disease in the Cancer Patient Psoriasis Secukinumab Ixekizumab TNF blockers Ixekizumab SubQ: 160 mg once, followed by 80 mg Q2 weeks x 6 doses, and then 80 mg Q4 weeks. Screening labs: TB, Hep B, Hep C, CBC, CMP Monitoring labs: CBC and CMP Q3 months No increased risk of leukemia/lymphoma or NMSC (so far) Treating Cutaneous Disease in the Cancer Patient Psoriasis Secukinumab Ixekizumab TNF blockers TNF blockers Promote tumor growth versus increase tumor surveillance Leukemia/Lymphoma may be increased NMSC may be increased 5

6 Treating Cutaneous Disease in the Cancer Patient Psoriasis Secukinumab Ixekizumab TNF blockers Cyclosporine Lymphoma NMSC Profound immunosuppression Length of therapy Treating Cutaneous Disease in the Cancer Patient Atopic dermatitis Azathioprine Dupilumab Treating Cutaneous Disease in the Cancer Patient Atopic dermatitis Azathioprine Dupilumab Azathioprine 50 mg/day > increase to mg/kg/day Screening labs: TPMT, CBC w/diff, CMP Monitoring: CBC, 2 weeks, then Q1month, then Q3months when dose is stable Increased NMSC Length of therapy 6

7 Treating Cutaneous Disease in the Cancer Patient Atopic dermatitis Azathioprine Dupilumab Dupilumab SubQ: 600 mg, followed by 300 mg Q2 weeks No lab monitoring is recommended No increased risk of leukemia/lymphoma or NMSC (so far) Treating Cutaneous Disease in the Cancer Patient Atopic dermatitis Azathioprine Dupilumab Cyclosporine Lymphoma NMSC Profound immunosuppression Length of therapy When the cancer IS the cutaneous disease Squamous cell carcinoma EGFR inhibitors Erlotinib 10% response Gefitinib 16 18% response PD 1 inhibitors Cemiplimab 50% response 3 mg/kg Q2weeks 7

8 When the cancer IS the cutaneous disease Basal cell carcinoma PTCH inhibitors (sonidegib versus vismodegib > longer PFS for sonidegib Vismodegib 150 mg daily (30 43% response) Sonidegib 200 mg daily (15 47% response) AEs: fatigue, muscle cramps, GI, alopecia > resolves in 1 3 months Screening labs: pregnancy test Sonidegib: CK, creatinine, LFTs PD 1 inhibitors? When the cancer IS the cutaneous disease Melanoma BRAF inhibitors (vemurafenib, dabrafenib) MEK inhibitors (trametinib, cobimetinib, binimetinib) Immune therapy Immune checkpoint inhibitors (anti CTLA 4, anti PD 1, anti PD L1) Merkel cell carcinoma PD 1/PD L1 inhibitors Question First line treatment for paraneoplastic disease is: A. Dapsone B. IVIG C. Treat the malignancy D. Rituximab 8

9 Paraneoplastic Disease Paraneoplastic pemphigus Systemic steroids Rituximab Screening labs: Hep B, Hep C, TB, CBC w/diff, CMP, IgG 375 mg/m2 x 4 weeks IVIG Screening labs: additional IgA Paraneoplastic Disease Paraneoplastic pemphigus Mycophenalate 1000 mg BID Screening labs: CBC, CMP Azathioprine Avoid cyclophosphamide and cyclosporine Paraneoplastic Disease Dermatomyositis Systemic steroids Methotrexate Azathioprine Hydroxychloroquine (rash only) mg daily Screening labs: Slit lamp eye exam (retinopathy), CBC, CMP Monitoring: CBC and CMP Q3 months x 6 months CBC and CMP Q6 months after 1 st 6 months Eye exam Q1year 9

10 Pyoderma gangrenosum/sweet s syndrome Paraneoplastic Disease Intralesional or systemic steroids Dapsone 25 mg daily, increasing by 25 mg weekly up to 100 mg daily AEs: Hemolysis, Neuropathy, Agranulocytosis, Methemoglobinemia Screening labs: G6PD, CBC, CMP Monitoring: CBC, LFTs Q1wk x 1 month Followed by Q2weeks x 2 months Q3months if dose stable PRN reticulocyte count and methemoglobin levels Paraneoplastic Disease Pyoderma gangrenosum/sweet s syndrome Colchicine 0.5 mg/day increasing to 2 mg/day in divided doses +/ dapsone AE: diarrhea Screening labs: CBC, UA Monitoring: CBC, UA monthly Followed by Q3months Avoid TNF inhibitors Cutaneous Adverse Events to Cancer Therapies Cytotoxic chemotherapy Immune therapy Targeted inhibitors Up to 75% incidence with EGFR inhibitors Immunecheckpoint inhibitors 40 50% incidence 10

11 Targeted therapies Curry JL, Torres cabala CA, Kim KB, et al. Int J Dermatol Immune checkpoint inhibitors CTLA4 inhibitors Ipilimumab Mar 2011, metastatic melanoma Tremelimumab failed Phase III trials PD 1 inhibitors Nivolumab Dec 2014, metastatic melanoma Pembrolizumab Sep 2014, metastatic melanoma PD L1 inhibitors Atezolizumab May 2016, urothelial carcinoma Avelumab March 2017, Merkel cell carcinoma Durvalumab May 2017, urothelial carcinoma Combination therapy Clinical trials, metastatic melanoma Question Using oral steroids will prevent the immune checkpoint inhibitor from working A. True B. False 11

12 Immunosuppression and Checkpoint inhibitors Systemic steroids and TNF inhibitors do not affect outcomes Acneiform eruption EGFR inhibitors Multikinase inhibitors MEK inhibitors HER2 inhibitors mtor inhibitors VEGF inhibitors RET inhibitors Treatment options: Doxycycline 100 mg BID Hydrocortisone 2.5% Bland emollient Clindamycin 1% Silvadene Dose reduction/cessation Acneiform eruption EGFR inhibitors Multikinase inhibitors MEK inhibitors HER2 inhibitors mtor inhibitors VEGF inhibitors RET inhibitors Intralesional triamcinolone Topical retinoid Topical dapsone Salicylic acid peels Oral prednisone 20 mg/day Oral acitretin 10 mg/day Oral isotretinoin mg/day 12

13 Spongiotic dermatitis CTLA4 inhibitors PD 1 inhibitors mtor inhibitors Treatment options: Topical steroids Systemic therapy: Oral steroids Dupilumab? Atopic dermatitis dosing Psoriasiform dermatitis PD 1 inhibitors Treatment options: Topical steroids Systemic therapy: Oral steroids Anti IL17 Lichenoid dermatitis CTLA 4 inhibitors PD 1 inhibitors Treatment options: Topical steroid Systemic therapy: Oral steroid 10 mg/day Anti IL 17 psoriasis dosing 13

14 Bullous pemphigoid PD 1 inhibitors Treatment options: Topical steroids Oral/IV steroids Rituximab 375 mg/m2 x 4 weeks Omalizumab 150 or 300 mg every 4 weeks Drug cessation Long latency (3 16 weeks) Safety first! Detailed history, lab review Communication with oncologist Summary Systemic therapies for skin cancers are expanding Toxicity profiles are decreasing Don t be afraid to use systemic therapies in paraneoplastic disease or CAEs 14