Ipilimumab and BRAF inhibitors cutaneous toxicity

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

T-cellCD-28 CTLA-4

Tumor

KillPD-1

Ipilimumab dermatologic toxicity:

Pruritus, Rash, vitiligo

Ipilimumab “plateau”

10

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

11

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

VEMURAFENIB cutaneous toxicity

Dabrafenib toxicity

Cutaneous