Ipilimumab was the first immunotherapy approved for metastatic melanoma in decades and is currently registered as a second-line treatment. However, new immunotherapies, in combination with ipilimumab, offer even better clinical outcomes for patients compared with single-agent treatments, at the expense of improved toxicity. The aim of this study was to evaluate the feasibility of ipilimumab outside the clinical trials and to identify survival predictors for treatment benefit. Data were collected on 47 advanced melanoma patients treated with ipilimumab between 2010 and 2015 at a single center. Association of clinical characteristics (including primary tumor characteristics), serum lactate dehydrogenase (LDH), erythrocyte sedimentation rate, absolute eosinophil, lymphocyte, and neutrophil count, neutrophil/lymphocyte and eosinophil/lymphocyte ratio with toxicity and clinical outcome were assessed using univariate and multivariate analysis. Median progression-free survival at a median follow-up of 10 months was 2.7 months and median overall survival was 9.8 months. Objective response was observed in 17% of patients and the disease control rate at week 24 was 40%. The 1- and 2-year survival rates documented were 40 and 28%, respectively. Significant association between high LDH level (>1.5× upper limit of normal) and decreased overall survival was demonstrated in uni- and multivariate analysis (hazard ratio [HR]: 3.554, 95% CI: 1.225-10.306, p = 0.019). Neither biomarkers nor clinical outcome were associated with toxicity. Using baseline serum LDH to identify patients most likely to benefit from ipilimumab therapy could serve as a simple and inexpensive biomarker of clinical outcome.

Dabrafenib is a potent BRAF inhibitor, which showed intracranial tumor activity. The purpose of our retrospective analysis was to evaluate the efficacy of dabrafenib for patients with melanoma brain metastasis (BM). We studied 30 BRAF mutant melanoma patients with BM, who received dabrafenib after local control of the brain between 2014 and 2017. Eastern Cooperative Oncology Group Performance Status (ECOG) was 0-2. The control arm consisted of 204 melanoma patients from our institutional melanoma database with BM and ECOG 0-2 treated with local therapies and/or chemotherapy, between 2003 and 2015. We found the intracranial disease control rate (DCR) was 83% including four (13%) complete remissions (CR), nine (30%) partial remissions (PR) and twelve (40%) stable diseases (SD) in contrast to five (17%) progressive diseases (PD). With a median follow-up of 14 months, median progression-free survival (PFS) and overall survival (OS) were 5.5 months, and 8.8 months, respectively. If calculated from BM onset, the OS turned to be 11.8 months on the dabrafenib arm, while it was only 6.0 months in the control arm (HR = 0.45, p = 0.0014). Higher risk of progression was observed with increasing ECOG (HR =4.06, p = 0.00027) and if more than 2 extracranial organs were involved (HR = 3.4, p = 0.0077). Elevated lactate dehydrogenase (LDH) was non-significantly associated with worse clinical outcome. Remarkable intracranial activity of dabrafenib in real practice was confirmed by our analysis.

No abstract

BRAF inhibitor vemurafenib achieved improved overall survival over chemotherapy and have been approved by the FDA and EMA for the treatment of BRAF-mutated metastatic melanoma. The aim of our retrospective analysis was to determine the efficacy and safety of vemurafenib therapy for BRAF mutated metastatic melanoma and subsequently to prove the clinical benefit for the studied 43 patients, based on real-life data. From November 2012 to October 2015 we have selected 43 BRAF mutated, metastatic melanoma patients, treated with vemurafenib. The median follow-up time was 15.9 months. We evaluated progression free survival (PFS), overall survival (OS) and toxicities. According to the AJCC staging system 70% of the patients had stage M1c metastasis, including 6 with stable brain metastasis. Objective responses were noted in 51.1%, the disease control rate was achieved in 79% of the patients. Complete responses were attained by 5 patients (11.6%). Median PFS was 6.48 (95% CI:4.8-15.0) months, median OS was 11.47 (95% CI:8.08-NA) months. We found significant association between LDH level and OS in univariate (p = 0.000613) and multivariate analysis (p = 0.0168). The most common adverse events (AEs) included follicular hyperkeratosis, rash, arthralgia and photosensitivity. Grade 3 AEs, such as cutaneous squamous-cell carcinoma, QTcB interval prolongation, rash, arthralgia were reported in 7 patients (17%). We had no Grade 4 side effects. Similar to the previously published data our analysis confirms the improved survival with vemurafenib treatment (11.47 months) in patients with BRAF V600 mutation. Vemurafenib therapy was well tolerated, the AE profile was almost consistent with the previously reported data of randomised clinical trials.

Purpose: To assess the prognostic role of sentinel lymph node status (SLN) in melanoma patients, a statistical comparison was performed with the application of already known prognostic factors, mutational occurrence of BRAF and NRAS in the primary tumor, as well as disease outcome. Methods: Our retrospective single-center study involved 159 melanoma cases, who underwent SLN biopsy. The following clinico-pathological data were collected: age, gender, location of primary tumor, Breslow thickness, ulceration degree, histological subtype, mitosis count, lymphovascular and perineural invasion, presence of tumor-infiltrating lymphocytes, regression signs, mutations of BRAF and NRAS of the primary tumors, and SLN status. Results: From the studied clinico-pathological factors, only Breslow thickness increased the risk of SLN positivity (p = 0.025) by multivariate analysis, while neither BRAF nor NRAS mutation of the primary tumor proved to be a predictor of the SLN status. While the NRAS-mutant subgroup showed the most unfavorable outcome for progression-free and distant metastasis-free survival, their rate of positive SLNs proved to be relatively lower than that of patient groups with BRAF mutation and double-wild-type phenotypes. Conclusion: Similarly to the importance of SLN positivity, NRAS mutation of the primary tumor proved to be an independent prognostic factor of progression. Therefore, despite negative SLN, this NRAS-mutant subgroup of patients still requires closer monitoring to detect disease progression.