American Board of Internal Medicine (ABIM) Certification Practice Exam

What combination therapy is recommended for a patient with metastatic BRAF-mutated melanoma?

1. Vemurafenib and cobimetinib

2. Fotemustine and dacarbazine

3. Pembrolizumab and ipilimumab

4. Nivolumab and atezolizumab

The correct answer is: Vemurafenib and cobimetinib

For a patient with metastatic BRAF-mutated melanoma, the recommended combination therapy is vemurafenib and cobimetinib. Both of these medications target the BRAF-MEK pathway, which is crucial in the development and progression of BRAF-mutated melanoma. Vemurafenib is a BRAF inhibitor that works by targeting the mutated BRAF protein, effectively blocking the signaling that leads to tumor growth. Cobimetinib is a MEK inhibitor that further disrupts the signaling pathway downstream of BRAF, enhancing the therapeutic efficacy against the melanoma. The rationale behind using this combination therapy is that it has been shown to provide improved outcomes compared to BRAF inhibition alone. This is primarily due to the ability of the MEK inhibitor to mitigate the development of resistance that often occurs with BRAF monotherapy. Studies have demonstrated that the combination can lead to a higher response rate, longer progression-free survival, and better overall survival than either drug used individually. While other therapies exist for melanoma treatment, such as immunotherapy with pembrolizumab and ipilimumab or nivolumab and atezolizumab, these strategies are generally reserved for different subgroups of melanoma patients or those without specific mutations. The combination of vemurafenib and