Ipilimumab and BRAF inhibitors cutaneous toxicity
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Ipilimumab and BRAF inhibitors cutaneous toxicity

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Some specific symptoms and signs of cutaneous toxicity for the new melanoma drugs

Some specific symptoms and signs of cutaneous toxicity for the new melanoma drugs

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    Ipilimumab and BRAF inhibitors cutaneous toxicity Ipilimumab and BRAF inhibitors cutaneous toxicity Presentation Transcript

    • Squamous carcinoma low grade. Vemurafenib
    • General considerations • Surgery: – At least 2 cm margin (body) – No sentinel node for lesion less 0,75- 1 mm – Lynphadenectomy: no survival benefit shown yet; prognostic value • Radiotherapy: no major indication. Abscopal effect • Drugs: adyuvant or metastatic setting
    • Adyuvant Interferon 1 year One node with microscopic infiltration: No Interferon New drugs in the adjuvant setting in clinical trials.
    • VITILIGO after Interferon treatment
    • Flow sheet for metastatic melanoma Bad performance, pluripathology, clinical fragility: Paliative Care CNS metastasis and good general situation: Radiotherapy. Dabrafenib selected patients REST: + 1. BRAF mutation: --- Vemurafenib or Dabrafenib+trametinib Chemotherapy or Ipilimumab Patients with BRAF mutated melanoma, without clinical “agresivity” can start also with Ipilimumab
    • Summary T-cell balance APC CD-28 CTLA-4 T-cell PD-1 Tumor Kill
    • Ipilimumab dermatologi c toxicity: Pruritus, Rash, vitiligo
    • Ipilimumab “plateau”
    • Phase I Drug-Related Grade 2 and 3 AEs (>5% Patients) VEMURAFENIB Toxicity at 960 mg BID dose (n=32) • Toxicities were monitored and managed with dose interruption and/or modification Arthralgia 34% cuSCC 31% Rash 25% • No discontinuations for AEs Nausea 16% Fatigue 13% Photosensitivity 16% Palmar-plantar dysesthesia 13% Pruritis 13% Lymphopenia 6% 10
    • Cutaneous SCC – Keratoacanthoma (KA) Subtype Characteristics of KA subtype • Raised button-like, central crater • Well-differentiated neoplasm with low probability of invasion/metastasis • Can grow rapidly; may involute and regress • Typically treated by excision • Observed with other agents (e.g., sorafenib) KA in the Phase I RG7204 Trial • Occurred on sun-exposed skin • Did not result in treatment discontinuation 11
    • VEMURAFENIB cutaneous toxicity
    • Dabrafenib toxicity Cutaneous