ipilimumab and braf inhibitors cutaneous toxicity
DESCRIPTION
Some specific symptoms and signs of cutaneous toxicity for the new melanoma drugsTRANSCRIPT
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Squamous carcinoma low grade. Vemurafenib
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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
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Adyuvant
Interferon 1 year
One node with microscopic infiltration: No Interferon
New drugs in the adjuvant setting in clinical trials.
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VITILIGO after Interferon treatment
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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
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Summary T-cell balance
APC
T-cellCD-28 CTLA-4
Tumor
KillPD-1
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Ipilimumab dermatologic toxicity:
Pruritus, Rash, vitiligo
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Ipilimumab “plateau”
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Toxicity at 960 mg BID dose (n=32)
Arthralgia 34%cuSCC 31%Rash 25%Nausea 16%Fatigue 13%Photosensitivity 16%Palmar-plantar dysesthesia 13%
Pruritis 13%Lymphopenia 6%
• Toxicities were monitored and managed with dose interruption and/or modification
• No discontinuations for AEs
Phase I Drug-Related Grade 2 and 3 AEs (>5% Patients)
VEMURAFENIB
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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
Cutaneous SCC – Keratoacanthoma (KA) Subtype
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VEMURAFENIB cutaneous toxicity
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Dabrafenib toxicity
Cutaneous