Efficacy and safety of BRAF inhibitors and anti-CTLA4 antibody in melanoma patients-real-world data.

Purpose: In the management of melanoma, BRAF inhibitors yield fast disease control; however, the duration of response does not last very long. Ipilimumab-an anti-CTLA4 antibody on the other hand-provides longer-lasting results of treatment but achieves less favorable responses. The aim of this study was to assess the efficacy and safety of novel drugs for advanced melanoma in daily routine practice.

Methods: A retrospective observational study was conducted on all Polish patients (1170 patients), diagnosed with advanced metastatic melanoma, treated with the following drugs: vemurafenib, dabrafenib, and ipilimumab. The antitumor efficacy of these agents was retrospectively assessed by Response Evaluation Criteria in Solid Tumors in the case of BRAF inhibitors and by Immune-Related Response Criteria in the case of ipilimumab therapy. Adverse events were assessed in relation to the morphologic parameters of blood, nephrotoxicity, and hepatotoxicity.

Results: The overall response to treatment with BRAF inhibitors (vemurafenib and dabrafenib) was similar with a slightly better outcome in the group treated with vemurafenib. Compared to clinical trials, the objective response rate was slightly worse for both BRAF inhibitors (30% and 42% for dabrafenib and vemurafenib, respectively), as well as the immune-related response for ipilimumab (1%). There was no significant difference in patient's response rates regardless of what lines of treatment (first, second, or next) vemurafenib was applied in. A few severe adverse events (mostly anemia and hyperbilirubinemia) were observed during treatment.

Conclusions: The lack of evidence in responses observed regardless of what line of treatment vemurafenib was applied in suggests there is no clinical reason for restricting BRAF inhibitors to only the first line of therapy. Our study confirms that novel agents brought about a major advancement in the management of melanoma. In line with literature, BRAF inhibitors and ipilimumab significantly improved the antitumor response rate with manageable adverse events.