BACKGROUND: Immunotherapy and targeted therapy are currently two alternative backbones in the therapy of BRAF-mutated malignant melanoma. However, predictive biomarkers that would help with treatment selection are lacking. METHODS: This retrospective study investigated outcomes of anti-programmed death receptor-1 monotherapy and targeted therapy in the first-line setting in patients with metastatic BRAF-mutated melanoma, focusing on clinical and laboratory parameters associated with treatment outcome. RESULTS: Data from 174 patients were analysed. The median progression-free survival (PFS) was 17.0 months (95% CI; 8-39) and 12.5 months (95% CI; 9-14.2) for immunotherapy and targeted therapy, respectively. The 3-year PFS rate was 39% for immunotherapy and 25% for targeted therapy. The objective response rate was 72% and 51% for targeted therapy and immunotherapy. The median overall (OS) survival for immunotherapy has not been reached and was 23.6 months (95% CI; 16.1-38.2) for targeted therapy, with a 3-year survival rate of 63% and 40%, respectively. In a univariate analysis, age < 70 years, a higher number of metastatic sites, elevated serum LDH and a neutrophil-lymphocyte ratio above the cut-off value were associated with inferior PFS regardless of the therapy received, but only serum LDH level and the presence of lung metastases remained significant predictors of PFS in a multivariate analysis. CONCLUSIONS: Present real-world data document the high effectiveness of immunotherapy and targeted therapy. Although targeted therapy had higher response rates, immunotherapy improved PFS and OS. While the prognostic value of LDH was confirmed, the potential use of blood cell count-derived parameters to predict outcomes needs further investigation.

• Klíčová slova
• BRAF mutation, immunotherapy, real-world data, targeted therapy,
• MeSH
• lidé MeSH
• melanom * farmakoterapie   genetika   patologie   MeSH
• nádory kůže * farmakoterapie   MeSH
• protoonkogenní proteiny B-Raf genetika   MeSH
• receptory domény smrti MeSH
• retrospektivní studie MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• BRAF protein, human MeSH Prohlížeč
• protoonkogenní proteiny B-Raf MeSH
• receptory domény smrti MeSH

PURPOSE: Combination treatment with BRAF and MEK inhibitors has demonstrated benefits on progression-free survival (PFS) and overall survival (OS) and is a standard of care for the treatment of advanced BRAF V600-mutant melanoma. Here, we report the 5-year update from the COLUMBUS trial (ClinicalTrials.gov identifier: NCT01909453). METHODS: Patients with locally advanced unresectable or metastatic BRAF V600-mutant melanoma, untreated or progressed after first-line immunotherapy, were randomly assigned 1:1:1 to encorafenib 450 mg once daily plus binimetinib 45 mg twice daily, vemurafenib 960 mg twice daily, or encorafenib 300 mg once daily. An updated analysis was conducted 65 months after the last patient was randomly assigned. RESULTS: Five hundred seventy-seven patients were randomly assigned: 192 to encorafenib plus binimetinib, 191 to vemurafenib, and 194 to encorafenib. The 5-year PFS and OS rates with encorafenib plus binimetinib were 23% and 35% overall and 31% and 45% in those with normal lactate dehydrogenase levels, respectively. In comparison, the 5-year PFS and OS rates with vemurafenib were 10% and 21% overall and 12% and 28% in those with normal lactate dehydrogenase levels, respectively. The median duration of response with encorafenib plus binimetinib was 18.6 months, with disease control achieved in 92.2% of patients. In comparison, the median duration of response with vemurafenib was 12.3 months, with disease control achieved in 81.2% of patients. Long-term follow-up showed no new safety concerns, and results were consistent with the known tolerability profile of encorafenib plus binimetinib. Interactive visualization of the data presented in this article is available at COLUMBUS dashboard. CONCLUSION: In this 5-year update of part 1 of the COLUMBUS trial, encorafenib plus binimetinib treatment demonstrated continued long-term benefits and a consistent safety profile in patients with BRAF V600-mutant melanoma.

• MeSH
• laktátdehydrogenasy MeSH
• lidé MeSH
• melanom * farmakoterapie   genetika   MeSH
• mutace MeSH
• nádory kůže * farmakoterapie   genetika   MeSH
• protokoly protinádorové kombinované chemoterapie škodlivé účinky   MeSH
• protoonkogenní proteiny B-Raf genetika   MeSH
• vemurafenib terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• binimetinib MeSH Prohlížeč
• BRAF protein, human MeSH Prohlížeč
• encorafenib MeSH Prohlížeč
• laktátdehydrogenasy MeSH
• protoonkogenní proteiny B-Raf MeSH
• vemurafenib MeSH

The dabrafenib plus trametinib (dab + tram) combination has demonstrated durable long-term efficacy in patients with BRAF V600-mutant metastatic melanoma. However, real-world data characterizing patients with long-term benefit are limited. DESCRIBE III was a global, observational, retrospective, chart review study in patients with unresectable or metastatic melanoma treated with dab monotherapy and/or dab + tram combination therapy as part of the Named Patient Program or Individual Patient Program. Overall, 509 patients were enrolled. Patients were categorized into three groups based on their observed treatment duration: long-term (on therapy ≥12 months), intermediate (on therapy ≥6 months and <12 months), and short-term (on therapy <6 months) duration of benefit. More patients in the short-term duration of benefit group had baseline characteristics associated with poor prognosis compared with the other two groups. Median lactate dehydrogenase (LDH) levels (368 U/L) at baseline were also higher in the short-term duration of benefit group. No new safety signals were identified. DESCRIBE III identified baseline characteristics associated with long-term benefit of dab + tram. Lower LDH level and <3 metastatic sites at baseline were associated with a longer duration of benefit, confirming that the findings from COMBI-d and COMBI-v are relevant to patients treated in a real-world setting.

• Klíčová slova
• BRAF V600, chart review, dabrafenib, melanoma, real-world, trametinib,
• Publikační typ
• časopisecké články MeSH