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Updated: Apr 25, 2026

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
Involution of eruptive melanocytic nevi on combination BRAF and MEK inhibitor therapy
Frank W Chen1, Diane Tseng2, Sunil Reddy3
1Dermatology Service, Veterans Affairs Palo Alto Health Care System, Palo Alto, California2Department of Dermatology, Pigmented Lesion and Melanoma Program, Stanford University Medical Center, Palo Alto, California.
Importance:
Eruptive melanocytic nevi (EMN) are characterized by the sudden onset of numerous melanocytic nevi and have been traditionally described in the setting of immunosuppression. Selective BRAF inhibitors such as vemurafenib cause multiple cutaneous adverse effects, including the formation of cutaneous squamous cell carcinoma, as well as EMN. We describe the first reported case, to our knowledge, of involution of BRAF inhibitor-induced EMN following the concomitant addition of a MEK inhibitor, cobimetinib.
Observations:
A woman in her 20s with a history of metastatic melanoma developed EMN while receiving therapy with vemurafenib, a selective BRAF inhibitor. After disease progression, the patient was placed on a clinical trial that combined vemurafenib with a MEK inhibitor, cobimetinib. Within months, we noted clinical involution of many of her EMN. In addition, numerous preexisting nevi were noted to fade in color on the dual regimen. Over a year after initiating this combination therapy, most of the patient's EMN were no longer clinically evident.
Conclusions And Relevance:
Our case report describing the involution of EMN supports data from previous clinical trials indicating that combination BRAF and MEK inhibition may reduce cutaneous proliferative effects that arise on BRAF inhibitor monotherapy. Further studies are necessary to characterize the biological mechanisms underlying this phenomenon.
Insights
Combination therapy with BRAF and MEK inhibitors may help resolve eruptive melanocytic nevi (EMN) that arise during BRAF inhibitor treatment for melanoma. This approach may also reduce other skin side effects.
Area of Science:
- Dermatology
- Oncology
- Pharmacology
Background:
- Eruptive melanocytic nevi (EMN) are typically associated with immunosuppression.
- Selective BRAF inhibitors, like vemurafenib, can induce EMN and other cutaneous adverse effects.
- The involution of BRAF inhibitor-induced EMN has not been previously reported.
Observation:
- A patient with metastatic melanoma developed EMN during vemurafenib therapy.
- The patient's EMN showed clinical involution after initiating combination therapy with vemurafenib and cobimetinib (a MEK inhibitor).
- Preexisting nevi also faded in color with the combination therapy.
Findings:
- The combination of BRAF and MEK inhibitors led to the involution of BRAF inhibitor-induced EMN.
- This combination therapy appeared to reduce the occurrence and severity of cutaneous side effects.
- Most EMN were no longer clinically apparent after a year of combination treatment.
Implications:
- Combination BRAF and MEK inhibition may mitigate cutaneous proliferative effects seen with BRAF inhibitor monotherapy.
- Further research is needed to understand the biological mechanisms behind this observed phenomenon.
- This finding supports the potential of combination therapy to manage adverse skin reactions in melanoma patients.
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