Impact of BRAF mutation and BRAF inhibition on melanoma brain metastases

Abstract

The impact of BRAF mutations in metastatic melanoma on the incidence of brain metastases and melanoma prognosis and the effect of BRAF inhibitors on the incidence of brain metastases has not been defined. Therefore, a retrospective analysis of patients with metastatic melanoma treated at three institutions was carried out to examine the impact of BRAF mutations and a BRAF inhibitor, vemurafenib, on the incidence of brain metastases. A retrospective review of 436 records revealed no difference in the incidence of brain metastases between patients with BRAF-mutated tumors versus those without (incidence rate ratio=1.11, 95% confidence interval: 0.80-1.53; P=0.53). A lower incidence of brain metastases was observed in patients with BRAF-mutated tumors who took vemurafenib before the development of brain metastases versus those who did not (incidence rate ratio=0.51, 95% confidence interval: 0.30-0.86; P=0.009). Although treatment with vemurafenib led to improvement in extracranial disease control, it did not significantly affect progression of existing intracranial disease and survival in these patients (P=0.7). Although our previous preclinical data have indicated that penetration of vemurafenib into the brain is limited, our retrospective analysis showed that there was a lower incidence of brain metastases in patients with BRAF-mutated tumors who took vemurafenib before the diagnosis of brain metastases.

Improved survival of patients with melanoma brain metastases in the era of targeted BRAF and immune checkpoint therapies

“…1,27 In addition, the lack of an association between BRAF status and MBM incidence was similar to that of several prior retrospective studies. To the best of our knowledge, this resulted in one of the largest MBM cohorts reported to date with the inclusion of patients receiving approved BRAF-targeted and immune checkpoint therapy.…”

“…The MBM incidence rate in the current study is consistent with past studies in which 44% of patients with melanoma with unresectable stage III/IV disease developed MBM. 1,27 In addition, the lack of an association between BRAF status and MBM incidence was similar to that of several prior retrospective studies. 5,8,27 However, BRAF status was unknown in approximately 37% of the patients in current study due to BRAF testing not being routinely conducted before the approval of vemurafenib in 2011, which may have impacted the results.…”

“…1,27 In addition, the lack of an association between BRAF status and MBM incidence was similar to that of several prior retrospective studies. 5,8,27 However, BRAF status was unknown in approximately 37% of the patients in current study due to BRAF testing not being routinely conducted before the approval of vemurafenib in 2011, which may have impacted the results. With regard to the timing of de novo MBM, patients were most likely to be diagnosed before or during the first line of systemic therapy (27% of all patients).…”

Incidence, patterns of progression, and outcomes of preexisting and newly discovered brain metastases during treatment with anti–PD‐1 in patients with metastatic melanoma

“…Gummadi et al demonstrated that patients with BRAF-mutated melanoma who received vemurafenib had a decreased incidence of brain metastases compared with those who did not. 16 Peuvrel et al found a 20% incidence of new MBM in patients treated with vemurafenib, 59% of whom had controlled SYS disease during CNS disease progression. 17 However, we found no studies assessing the real-world incidence of brain metastases during anti-PD-1 therapy.…”

“…However, to the best of our knowledge, data regarding how recently approved agents can affect the development of MBM are scarce. Gummadi et al demonstrated that patients with BRAF‐mutated melanoma who received vemurafenib had a decreased incidence of brain metastases compared with those who did not . Peuvrel et al found a 20% incidence of new MBM in patients treated with vemurafenib, 59% of whom had controlled SYS disease during CNS disease progression .…”