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Melanoma brain metastases: intracranial anti-tumour activity of Encorafenib plus Binimetinib


Over 60% of patients with stage IV melanoma may develop brain metastases, resulting in a significantly increased morbidity and poor overall prognosis.
Clinical data for melanoma brain metastases ( MBM ) treatments are limited, as controlled studies often exclude patients with untreated brain metastases.

Researchers have conducted a multicenter, retrospective case series investigation with consecutive patients with BRAF-mutant melanoma brain metastases who were treated with BRAF inhibitor Encorafenib ( Braftovi ) plus MEK inhibitor Binimetinib ( Mektovi ) to evaluate the antitumor response with this combination.

Assessments included intracranial, extracranial and global objective response rates ( ORRs; percentage of complete [ CR ] + partial [ PR ] responses ) evaluated by modified RECIST version 1.1; clinical benefit rate ( CBR; percentage of CR + PR + stable disease [ SD ] as best response ); time to response, duration of response, and safety.

A total of 17 patients with stage IV BRAF-mutant melanoma brain metastases who received Encorafenib plus Binimetinib in centers in the United States were included.
Patients had received a median of 2 prior lines of treatment over a median of 520 days since their melanoma diagnosis ( median of 55 days since diagnosis of melanoma brain metastases ). Of the patients included, 82% had prior treatment with BRAF/MEK inhibitors.

The intracranial ORR was 35% ( with 3 CRs and 3 PRs ) and CBR was 76%, with a median duration of response of 17 weeks.

Eight patients with either stable disease or a response were still ongoing treatment at the time of the analysis.

Among the 14 patients with melanoma brain metastases and with prior BRAF/MEK inhibitor treatment, the intracranial ORR was 21% and CBR was 71%.
Similar outcomes were observed for extracranial and global responses.

The safety profile for Encorafenib plus Binimetinib was similar to that observed in patients with melanoma without brain metastases.

In conclusion, combination therapy with Encorafenib plus Binimetinib elicited intracranial activity in patients with BRAF-mutant melanoma brain metastases, including in patients previously treated with BRAF/MEK inhibitors. ( Xagena )

J Lutzky J et al, Annals of Oncology, Volume 30, Issue Supplement_5, 2019

XagenaMedicine_2019



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