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

1. Squamous carcinoma low grade. Vemurafenib

2. 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

3. Adyuvant
Interferon 1 year
One node with microscopic
infiltration: No Interferon
New drugs in the adjuvant setting in
clinical trials.

4. VITILIGO after
Interferon treatment

5. 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

6. Summary T-cell balance
APC
CD-28
CTLA-4
T-cell
PD-1
Tumor
Kill

7. Ipilimumab
dermatologi
c toxicity:
Pruritus,
Rash,
vitiligo

9. Ipilimumab “plateau”

10. 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

11. 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

12. VEMURAFENIB cutaneous toxicity

13. Dabrafenib toxicity
Cutaneous