Search

Between January 2007 and April 2014, 464 Danish patients received high-dose (HD) interleukin-2 (IL-2) and interferon (IFN) as first-line treatment for metastatic melanoma. Our data represent the largest cohort of patients with metastatic melanoma worldwide, with relevant data on all patients and no patients lost to follow-up. Data have been gathered in a national database on the treatment of metastatic melanoma established since 2011. One hundred eighteen patients (25%) obtained an objective response rate (ORR) to treatment with a median progression-free survival (PFS) of 3.4 months and a median overall survival (OS) of 14.2 months. Furthermore, 2-, 3- and 5-year survival was 32.0%, 23.2% and 16.6%, respectively. Ipilimumab as second-line therapy has been used since July 2010. We divided patients in two subgroups before and after this date to evaluate the effects of new treatment strategies. Patient characteristics, ORR and PFS were comparable in the two subgroups. Survival was significantly improved after 2010, with an increase in median OS from 12.2 to 16.0 months and in 5-year OS from 12.5% to 20.7%. Our data confirm that HD IL-2/IFN as first-line therapy in metastatic melanoma leads to long-term survival in a subset of treated patients. Potentially, IL-2/IFN might represent a treatment option in patients with active melanoma after established initial treatment with checkpoint inhibitors and BRAF/MEK-targeted therapies. • Long-term survival of patients with metastatic melanoma. • High-dose interleukin-2. • Impact of subsequent antineoplastic therapy. [ABSTRACT FROM AUTHOR]

Abstract Between 2010 and 2015, pivotal trials with strict enrolment criteria led to the approval of several new treatments for metastatic melanoma (MM). We sought to determine the impact of these treatments in the 'real world'. We took advantage of the Danish MM database (DAMMED), which contains data on the entire, unselected population diagnosed with MM within Denmark. All MM cases (excluding ocular MM, n = 837) diagnosed in three non-consecutive years marked by major changes in the first-line treatments (2012: interleukin-2 and BRAF inhibitors; 2014: anti–CTLA-4: Cytotoxic T-Lymphocyte Antigen 4 and 2016: anti–PD-1: programmed cell death protein 1 and MEK inhibitors) were retrieved. Patients were grouped into 'trial-like' and 'trial-excluded' based on the common trial eligibility criteria. In the 'trial-like' population (39% of all MM), the median overall survival (OS) was not reached in 2016 versus 18.8 months in 2014 (hazard ratio [HR] 0.52, 95% confidence interval [CI] 0.35–0.75; p = 0.0005) and 16.5 months in 2012 (HR 0.41, 95% CI 0.27–0.63; p < 0.0001). In the 'trial-excluded' population (61% of all MM), 75% had brain metastases and/or (performance status) PS ≥ 2. Here, the median OS improved to 6.9 months in 2016 versus 5.2 months in 2014 (HR 0.66, 95% CI 0.52–0.84; p = 0.0008) and 4.2 months in 2012 (HR 0.66, 95% CI 0.52–0.84; p = 0.0007). Subgroup analysis of the BRAF wild-type population showed an improved 1-year survival rate in 2016 versus 2014 (35.9% vs 18.8%, p = 0.0153). In conclusion, the introduction of modern treatments has led to an improved survival of real-world patients with MM, regardless of their eligibility to clinical trials and the BRAF status. These data support the application of modern treatments to patient populations which are not represented in pivotal trials. Highlights • Patients with similar features of those enrolled in melanoma immunotherapy trials obtained survival benefit in the real world. • The immunotherapy trial eligibility criteria excluded most patients with melanoma. • Modern treatments led to an improved survival of patients who are not represented in immunotherapy trials. [ABSTRACT FROM AUTHOR]