Real-World Data on Clinical Outcomes and Treatment Management of Advanced Melanoma Patients: Single-Center Study of a Tertiary Cancer Center in Switzerland.

BACKGROUND: Immune checkpoint inhibitors (ICIs) and BRAF/MEK inhibitors (BRAF/MEKi) have drastically changed the outcomes of advanced melanoma patients in both the resectable/adjuvant and unresectable/metastatic setting. In this follow-up analysis of real-world data, we aimed to investigate the clinical management and outcomes of advanced melanoma patients in a tertiary referral center in Switzerland approximately a decade after the introduction of ICIs and BRAF/MEKi into clinical use. Moreover, we aimed to compare the results with seminal phase 3 trials and to identify areas of high unmet clinical need. METHODS: This single-center retrospective cohort study analyzed the melanoma registry of the University Hospital Zurich, a tertiary cancer center in Switzerland, and included patients treated in the resectable/adjuvant (n = 331) or unresectable/metastatic setting (n = 375). RESULTS: In the resectable setting, adjuvant anti-PD1 or BRAF/MEKi showed a 3-year relapse-free survival (RFS) of 53% and 67.6%, respectively, and the overall median RFS was 50 months. Patients with lymph node plus in-transit metastases or with distant metastases prior to commencing adjuvant treatment had a significantly reduced overall survival (OS). In 10.9% of patients, the treatment was stopped due to toxicity, which did not affect RFS/OS, unless the duration of the treatment was <3 months. Following a relapse of the disease during the first adjuvant treatment, the median progression-free survival (PFS2) was only 6.6 months; outcomes were particularly poor for relapses that were unresectable (median PFS2 3.9 months) or occurred within the first 2 months (median PFS2 2.7 months). A second adjuvant treatment for patients with resectable relapses still showed efficacy (median RFS2 43.7 months). Elevated LDH levels in patients with an unresectable relapse was correlated with a strong reduction in OS2 (HR 9.84, p = 0.018). In the unresectable setting, first-line anti-PD1, anti-CTLA4/PD1 combination, or BRAF/MEKi showed a 5-year OS of 46.5%, 52.4%, and 49.2%, respectively. In a multivariate analysis, elevated LDH levels or the presence of brain metastases substantially shortened OS (HR > 1.78, p < 0.035). There was a non-significant trend for the improved survival of patients treated with anti-CTLA4/PD1 compared to anti-PD1 (HR 0.64, p = 0.15). After a progression on first-line therapy, the median OS2 was reduced to below two years. Elevated LDH (HR 4.65, p < 0.001) levels and widespread disease with at least three metastatic sites, particularly bone metastases (HR 2.62, p = 0.026), affected OS2. CONCLUSION: Our study offers real-world insights into the clinical management, treatment patterns, and outcomes of advanced melanoma patients in both the adjuvant and unresectable setting. Early relapses in patients undergoing adjuvant treatment pose a particular challenge but these patients are generally excluded from first-line trials. The approved first-line metastatic treatments are highly effective in the real-world setting with 5-year OS rates around 50%. However, outcomes remain poor for patients with brain metastases or who fail first-line treatment.

Noncutaneous Melanomas: A Single-Center Analysis.

BACKGROUND: The optimal treatment algorithm for noncutaneous melanomas must yet be established. OBJECTIVE: To compare systemic treatment-relevant mutational status, metastatic pattern and response to systemic treatment in noncutaneous melanoma. METHODS: Retrospective single-center study analyzing 64 noncutaneous melanoma patients treated between January 2006 and September 2013. RESULTS: c-KIT mutations were found exclusively in vulvovaginal melanoma (4/7). Overall status for NRAS and BRAF mutations was low (1/7 and 0/21 detected mutations, respectively). Seven out of 7 vulvovaginal and 6/13 sinonasal melanomas first metastasized to lymph nodes, whereas 18/22 ocular melanomas first metastasized to the liver. Response to systemic treatment in vulvovaginal melanomas was best for imatinib with a disease control rate of 3/3 and overall for ipilimumab with a disease control rate of 3/10. Sorafenib was associated with adverse drug reactions (6/13) and poor results. CONCLUSION: Noncutaneous melanomas show few tumor-signaling pathway mutations and distinct metastasization patterns. Immunotherapy induces response rates in mucosal melanoma similar to those in cutaneous melanoma.

CoCo trial: Color-coded blood pressure Control, a randomized controlled study.

BACKGROUND: Inadequate blood pressure (BP) control is a frequent challenge in general practice. The objective of this study was to determine whether a color-coded BP booklet using a traffic light scheme (red, >180 mmHg systolic BP and/or >110 mmHg diastolic BP; yellow, >140-180 mmHg systolic BP or >90-110 mmHg diastolic BP; green, ≤140 mmHg systolic BP and ≤90 mmHg diastolic BP) improves BP control and adherence with home BP measurement. METHODS: In this two-group, randomized controlled trial, general practitioners recruited adult patients with a BP >140 mmHg systolic and/or >90 mmHg diastolic. Patients in the control group received a standard BP booklet and the intervention group used a color-coded booklet for daily home BP measurement. The main outcomes were changes in BP, BP control (treatment goal <140/90 mmHg), and adherence with home BP measurement after 6 months. RESULTS: One hundred and twenty-one of 137 included patients qualified for analysis. After 6 months, a significant decrease in systolic and diastolic BP was achieved in both groups, with no significant difference between the groups (16.1/7.9 mmHg in the intervention group versus 13.1/8.6 mmHg in the control group, P=0.3/0.7). BP control (treatment target <140/90 mmHg) was achieved significantly more often in the intervention group (43% versus 25%; P=0.037; number needed to treat of 5). Adherence with home BP measurement overall was high, with a trend in favor of the intervention group (98.6% versus 96.2%; P=0.1). CONCLUSION: Color-coded BP self-monitoring significantly improved BP control (number needed to treat of 5, meaning that every fifth patient utilizing color-coded self-monitoring achieved better BP control after 6 months), but no significant between-group difference was observed in BP change. A markedly higher percentage of patients achieved BP values in the normal range. This simple, inexpensive approach of color-coded BP self-monitoring is user-friendly and applicable in primary care, and should be implemented in the care of patients with arterial hypertension.

Uncontrolled arterial hypertension in primary care--patient characteristics and associated factors.

PRINCIPLES: Most patients with arterial hypertension are treated in primary care. The objective is to assess characteristics of patients with uncontrolled arterial hypertension and its associated determinants in Swiss primary care. METHOD: Data on 122 adult patients with uncontrolled hypertension (mm Hg >140 systolic and/or >90 diastolic) was collected from the baseline data of the on-going randomised controlled "CoCo" trial: Colour-coded Blood Pressure Control. Patient and general practitioner characteristics were analysed to investigate the relationship between BP and patient characteristics. RESULTS: From October 2009 to March 2011 30 general practitioners recruited 122 patients; median age 64 years (IQR 54.8-72), 50% male, median BMI 28.3 kg/m2 (IQR 25.3-31.7), 21.5% smokers. 65.6% performed home blood pressure measurement, 88.5% received pharmacological treatment, 41.8% mono-therapy. Most frequent dual drug combinations: diuretics/angiotensin-receptor-blockers (33.3%), angiotensin-converting-enzyme-inhibitors/beta blockers (both 28.1%). BMI, smoking and age were independent predictors for elevated systolic blood pressure when controlled for gender, home blood pressure measurement, education, pulse rate and number of antihypertensive substances. We found a significant non-linear association between systolic blood pressure and number of antihypertensive substances. Age and any amount of antihypertensive substances were independently and inversely correlated with diastolic blood pressure. The findings did not change when additionally controlled for general practitioner clustering effect. CONCLUSION: Smoking and high BMI are strong and independent factors associated with higher blood pressure levels in patients with uncontrolled arterial hypertension. A high rate of monotherapy and a decrease in the incremental gain on blood pressure control when more antihypertensive agents are used highlight the importance of adequate pharmacological treatment as well as risk factor control.