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Progress in the treatment of cerebral metastases in advanced melanoma

Publication |
2018

Abstract

Brain metastases in generalized melanoma represent a major therapeutic problem of current oncology. In 2017, three major studieswere published on this issue.

The COMBI MB study utilized the previously published experience of the BREAK MB study and inpatients with proven BRAF mutation, combination of BRAF and MEK inhibitors were used to treat patients with brain metastases.The results demonstrated the high efficacy of this treatment. 58% ORR was achieved in asymptomatic non-treated patients versus39.2% ORR in patients treated with dabrafenib monotherapy. Another option is treatment with immunotherapy using anti-PD1and anti-CTLA4 antibodies.

In comparison with the CheckMate 204 and ABC studies, the results are similar. For the CheckMate 204study, ORR was also 55%, but the number of CR was higher, 21% to 4% in COMBI MB.

In the ABC study, ORR was 42% for IPI + NIVOcombination therapy and 20% for monotherapy with nivolumab. No major differences were seen in the 6-month PFS achievedby 44 % of patients in COMBI MB, 65% in CheckMate, 46% in the ABC study (IPI + NIVO) and 28 % in nivolumab monotherapy.

Theresults confirmed the similar effectiveness of treatment of brain metastases as targeted treatment of MEK and BRAF inhibitors, aswell as immunotherapy. A high percentage of responses is not associated with their long-term duration, median 6.5 months (95%CI, 4.9-10.3), compared to the same treatment in patients without cerebral metastases, median 12.9 months (95 % CI, 9, 4-19, 5).In terms of historical data on the treatment of brain metastases with radiotherapy, the duration of the response increased from3.4 months (10) to 6.5 months.