Long-term survival of patients with advanced melanoma treated with BRAF-MEK inhibitors.

Recent results of patients with advanced melanoma treated with first-line BRAF-MEK inhibitors in clinical trials showed 5-year survival in one-third of patients with a median overall survival (OS) of more than 2 years. This study aimed to investigate these patients' real-world survival and identify the characteristics of long-term survivors. The study population consisted of patients with advanced cutaneous melanoma with a BRAF-V600 mutated tumor who were treated with first-line BRAF-MEK inhibitors between 2013 and 2017. Long-term survival was defined as a minimum OS of 2 years from start therapy. The median progression-free survival (mPFS) and median OS (mOS) of real-world patients ( n = 435) were respectively 8.0 (95% CI, 6.8-9.4) and 11.7 (95% CI, 10.3-13.5) months. Two-year survival was reached by 28% of the patients, 22% reached 3-year survival and 19% reached 4-year survival. Real-world patients often had brain metastases (41%), stage IV M1c disease (87%), ECOG PS ≥2 (21%), ≥3 organ sites (62%) and elevated LDH of ≥250 U/I (49%). Trial-eligible real-world patients had an mOS of 17.9 months. Patients surviving more than 2 years ( n = 116) more often had an ECOG PS ≤1 (83%), normal LDH (60%), no brain metastases (60%), no liver metastases (63%) and <3 organ sites (60%). Long-term survival of real-world patients treated with first-line BRAF-MEK inhibitors is significantly lower than that of trial patients, which is probably explained by poorer baseline characteristics of patients treated in daily practice. Long-term survivors generally had more favorable characteristics with regard to age, LDH level and metastatic sites, compared to patients not reaching long-term survival.

[Recent treatment results for metastatic melanoma: data from the Dutch Melanoma Treatment Registry]. / Recente behandelresultaten van uitgezaaid melanoom.

OBJECTIVE: To evaluate treatment strategies and survival of patients with unresectable stage IIIc or IV melanoma since the 2012 introduction of new drugs in the Netherlands. DESIGN: Prospective cohort study. METHOD: We analysed data from the Dutch Melanoma Treatment Registry (DMTR) regarding patients diagnosed with unresectable stage IIIc or IV melanoma in the period of 1 July 2012 to 31 December 2015. We estimated survival times using the Kaplan-Meier method. The relationship between year of diagnosis and survival was estimated using Cox regression analysis, adjusted for age, WHO performance status, lactate dehydrogenase values, stage, brain metastases and distant metastases. RESULTS: Out of 2,768 registered patients, approximately three-quarters received systemic therapy. This treatment was subject to change every year. Median survival was 10.7 months (95% CI: 9.6-13.2) in 2012 and 13.8 months (95% CI: 11.8-15.6) in 2015. Median survival for patients receiving systemic therapy was 17.1 months in 2015. 2-year survival in this period increased from 23% to 40%. Patients diagnosed in 2015 had better survival than patients of 2014 (hazard ratio (HR) 0.82; 95% CI: 0.73-0.93). This was also true for patients receiving systemic therapy (HR: 0.79; 95% CI: 0.69-0.91). CONCLUSION: Fast availability of new drugs, initiated by the then minister of VWS (health, welfare and sport) and the professional organisation, has thoroughly changed treatment of unresectable stage IIIc and IV melanoma. Data from the DMTR indicate safe use of these new drugs in daily practice and improved survival of advanced-melanoma patients in recent years.