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Published on: September 8, 2021
Vemurafenib beyond progression in a patient with metastatic melanoma: a case report
Antonio M Grimaldi1, Ester Simeone, Marco Palla
1aDivision of Melanoma, Cancer Immunotherapy and Innovative Therapies bDivision of Melanoma and Skin Cancer cDepartment of Diagnostic Imaging, Radiant and Metabolic Therapy, Division of Radiology dDivision of Radiotherapy, Istituto Nazionale Tumori Fondazione Pascale, Naples, Italy.
Abstract:
The prognosis of metastatic melanoma has changed markedly in recent years because of the advent of newer targeted therapies such as BRAF inhibitors. However, the response to BRAF inhibitor therapy is frequently nondurable in patients with advanced melanoma. Novel approaches are thus needed to overcome resistance to these agents and to improve the management of advanced melanoma patients after disease progression. Here, we present the case of a 44-year-old man diagnosed with advanced melanoma in July 2010, harboring a BRAF mutation. Melanoma progressed during first-line chemotherapy with dacarbazine, but showed significant benefit after the initiation of vemurafenib on August 2011. Six months later, the patient experienced disease progression in left-obturator lymphadenopathy; still, anti-BRAF treatment was continued together with stereotactic radiotherapy, and was interrupted only shortly for intestinal occlusion secondary to melanoma metastasis of the bowel. When his conditions were stable, after 1 month of vemurafenib treatment discontinuation, anti-BRAF therapy was reinitiated, with a positive outcome. Vemurafenib treatment was definitively discontinued for disease progression in the brain, peritoneum, lymph node, intestine, and skin in March 2013, after about 20 months from initiation, and the patient died a few weeks later. The clinical case presented here shows that treatment beyond progression with vemurafenib can yield a survival benefit in melanoma patients whose disease progresses in a few sites, which can be treated with locoregional therapies. This clinical strategy needs further validation in prospective clinical trials.
Insights
Treatment beyond progression with BRAF inhibitors like vemurafenib may extend survival in advanced melanoma patients. This strategy shows promise for managing disease progression in select cases, warranting further clinical trials.
Area of Science:
- Oncology
- Dermatology
- Medical Oncology
Background:
- Metastatic melanoma prognosis has improved with targeted therapies like BRAF inhibitors.
- However, BRAF inhibitor therapy often leads to non-durable responses in advanced melanoma.
- Novel strategies are needed to overcome resistance and improve outcomes after disease progression.
Observation:
- A 44-year-old man with BRAF-mutated advanced melanoma initially progressed on dacarbazine chemotherapy.
- He experienced significant benefit from vemurafenib (a BRAF inhibitor) starting in August 2011.
- Disease progression occurred 6 months later, but vemurafenib was continued with radiotherapy, with temporary interruption for complications.
Findings:
- Reinitiation of vemurafenib after a brief discontinuation due to complications led to a positive outcome.
- The patient received vemurafenib for approximately 20 months before definitive discontinuation due to widespread progression.
- Treatment beyond progression with vemurafenib, combined with locoregional therapies for limited progression sites, demonstrated a survival benefit.
Implications:
- Continuing BRAF inhibitor therapy beyond disease progression can be a viable strategy in advanced melanoma.
- This approach may offer survival benefits, particularly when progression occurs in limited, treatable sites.
- Further prospective clinical trials are necessary to validate the efficacy and safety of treatment beyond progression with BRAF inhibitors.
