Real Life Clinical Management and Survival in Cutaneous Malignant Melanoma: the Italian Clinical National Melanoma Registry (CNMR) Experience

Abstract

Background: Cutaneous malignant melanoma (CMM) is one of the most aggressive types of skin cancer. Currently, innovative approaches such as target therapies and immunotherapies have been introduced in clinical practice for the treatment of metastatic CMM. Data of clinical trials and real life studies that evaluate the outcomes of these therapeutic associations are necessary to establish their clinical utility. The aim of this study is to investigate the types of oncological treatments employed in the real-life clinical management of patients with advanced CMM in several Italian centers which are part of the Clinical National Melanoma Registry (CNMR), and the oncological outcomes obtained. Methods: CNMR collects data of patients with a histologically confirmed diagnosis of primary CMM treated in one of the 38 Italian institutions (hospitals, research institutes, etc.) participating in the network. Melanoma-specific survival and Overall survival were calculated. Kaplan-Meier curves and medians of OS and 95% CI are presented overall and by immunotherapy and target treatments. The Log-rank test compared curves by treatments. Multivariate Cox regression models were used to estimate the hazard ratios adjusting for confounders and other prognostic factors. Results: The median follow-up time was 36 months (range 1.2-185.1). 787 CMM were included in the analysis with completed information about therapies.Global immunotherapy showed a significant improved survival compared with all other therapies (p=0.001). 75% was the highest reduction of death reached by nivolumab/pembrolizumab immunotherapy (anti-PD1 HR=0.25 95% CI 0.14-0.42), globally immunotherapy was significantly associated with improved survival, either for anti-CTL A4 monotherapy or combined with anti-PD1 (HR=0.47;95% CI 0.33-0.66 and HR=0.26; 95% CI 0.15-0.46, respectively). Conclusions: The nivolumab/pembrolizumab and the combination of ipilimumab can be considered the best therapy to improve survival in a real-world-population. The CNMR can complement clinical registries with the intent of improving cancer management and standardizing cancer treatment.

Temporal Trends in the Incidence and Mortality of Skin Malignant Melanoma in China from 1990 to 2019

“…Figure 3 displays the concentrated risk of SMM in China in the elderly stage, which may be related to the impaired immune response of the elderly to malignant tumors and infections [ 24 ]. Although the SMM ASMR has declined due to China's economic development [ 25 ], progression in medical technology [ 2 , 26 ], and per-capita education level [ 26 ], the SMM CMR of the elderly has continued to increase due to increasing size of their population. Zeng and Wang [ 27 ] and Chen and Liu [ 28 ] estimated that by 2050, there will be 329 million people older than 65 years, accounting for 25% of the Chinese population, and the growth rate of people older than 80 years will be even greater, increasing from 0.9% in 2000 to 7.2% in 2050.…”

“…Skin malignant melanoma (SMM) is the most aggressive and prevalent form of skin cancer that is characterized by a poor prognosis, frequent metastasis, and high mortality rate [ 1 , 2 ]. Melanoma only accounts for 1-2% of all cancer cases worldwide and less than 5% of skin cancers, but is responsible for around 95% of deaths due to skin cancer [ 3 ].…”

Nanotechnology Addressing Cutaneous Melanoma: The Italian Landscape

“…The results of this research showed that immunotherapy significantly improved the patient's survival in a real-world population. Moreover, the study pointed out that the combination of nivolumab/pembrolizumab with ipilimumab is the best therapy for the clinical management of advanced melanoma [92] (Figure 1). Anyway, even if recent studies showed that combination therapy has a greater efficacy than monotherapy, it is associated to a higher incidence of adverse side effects.…”

“…BRAFi and MEKi combination is the most used targeted therapy (lower panel, right). Data elaborated from[92].…”

Quality of Life Predictors in Patients With Melanoma: A Machine Learning Approach

“…In 2021, approximately 101,280 new melanoma cases were predicted in the United States (1,2). Currently, innovative approaches such as target therapies and immunotherapies have been introduced in clinical practice for the treatment of cutaneous melanoma (3). More in detail, target therapies are based on the use of drugs targeting specific genetic alterations in candidate genes, blocking specific pathways implicated in the oncogenesis of melanoma (3).…”