Management of metastatic melanoma: improved survival in a national cohort following the approvals of checkpoint blockade immunotherapies and targeted therapies

AbstractBackgroundImmune checkpoint blockade (ICB) and BRAFV600-targeted therapy have demonstrated substantial clinical efficacy for patients with stage 4 melanoma in clinical trials; however, their impact on survival and barriers to treatment in the “real-life” setting remains unknown.MethodsPatients who presented with cutaneous melanoma during 2004 –2015 using the National Cancer Database, which comprises >  70% of all newly diagnosed cancers in the U.S., were evaluated for predictors of presenting with stage 4 disease and receiving ICB, and for their associated unadjusted and risk-adjusted overall survival (OS).Results17,975 patients presented with stage 4 metastatic cutaneous melanoma. Overall, patients who presented after the FDA ’s initial approvals (starting in 2011) for ICB and BRAFV600-targeted therapy demonstrated a 31% relative improvement in 4-year OS (p 
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research

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AbstractImmune checkpoint blockers (ICB) have revolutionized cancer therapy. However, complete response is observed in a minority of patients and most patients develop immune-related adverse events (irAEs). These include colitis, which can be treated with anti-tumor necrosis factor (TNF) antibodies such as Infliximab. In a recent issue of the Journal for ImmunoTherapy of Cancer, Badran et al. reported that co-administering Infliximab together with ICB to five cancer patients prevents colitis recurrence, with four of them exhibiting overall disease stability. The basis for this treatment strategy stemmed from our pre-clinic...
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
ConclusionsThe tolerability of the combined checkpoint blockade in UM may possibly be better than in trials on cutaneous melanoma. This study implies that combined checkpoint blockade represents the hitherto most effective treatment option available for metastatic UM available outside of clinical trials.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
Conclusion.Novel treatments such as immunotherapy provide significant hope for patients. This may influence their preference for immunotherapy over and above the usual considerations of the trade‐off between efficacy and toxicity. Careful counsel and individualized patient resources may further facilitate treatment decision‐making.Implications for Practice.This study highlighted some of the misconceptions held by patients that need to be addressed when discussing the possibility of receiving treatment with immunotherapy for advanced melanoma. Patients placed a lot of importance on high‐profile anecdotes rather than t...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Melanoma and Cutaneous Malignancies Source Type: research
Yicheng Ni Cancer remains a major cause of death globally. Given its relapsing and fatal features, curing cancer seems to be something hardly possible for the majority of patients. In view of the development in cancer therapies, this article summarizes currently available cancer therapeutics and cure potential by cancer type and stage at diagnosis, based on literature and database reviews. Currently common cancer therapeutics include surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy. However, treatment with curative intent by these methods are mainly eligible for patients with localized diseas...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Skalnikova National cancer databases document that melanoma is the most aggressive and deadly cutaneous malignancy with worldwide increasing incidence in the Caucasian population. Around 10% of melanomas occur in families. Several germline mutations were identified that might help to indicate individuals at risk for preventive interventions and early disease detection. More than 50% of sporadic melanomas carry mutations in Ras/Raf/mitogen-activated protein kinase (MAPK/MEK) pathway, which may represent aims of novel targeted therapies. Despite advances in targeted therapies and immunotherapies, the outcomes in metasta...
Source: Genes - Category: Genetics & Stem Cells Authors: Tags: Review Source Type: research
grave;res J Abstract Immunotherapy has become a standard of care in oncology, following the recent approvals of cytotoxic T-lymphocyte-associated protein-4 and programmed cell death-1 inhibitors in lung cancer, melanoma, renal cell carcinoma, Hodgkin's lymphoma, bladder, head and neck cancers. Besides their efficacy, these agents also generate specific immune-related adverse events. Due to the increasing prescription of immune-checkpoint inhibitors, the incidence of immune toxicity will continue to rise. The awareness of immune-related adverse events is key to ensuring both diagnosis and management of the possible...
Source: Respiratory Care - Category: Respiratory Medicine Authors: Tags: Eur Respir Rev Source Type: research
This study evaluated the therapeutic and survival disparities among patients with advanced MMel based on hospital volume using the National Cancer Database (NCDB). METHODS: A retrospective analysis using regression models and Kaplan-Meier estimates was performed from the data obtained from the NCDB on patients with MMel diagnosed in 2004 through 2015. RESULTS: A total of 40,676 patients with MMel were treated at 1,260 facilities. Multivariable analysis showed that facility volume was an independent predictor of overall survival (P
Source: Journal of the National Comprehensive Cancer Network : JNCCN - Category: Cancer & Oncology Tags: J Natl Compr Canc Netw Source Type: research
ConclusionOur results suggest that secondary resistance to immunotherapies can arise upon selection for new oncogenic variants that mediate T cell exclusion. To identify the spectrum of underlying mechanisms of therapeutic resistance, similar evaluation for the emergence of tumor-intrinsic alterations in resistant lesions should be done prospectively at the time of relapse in a range of additional patients developing secondary resistance.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
ConclusionIn summary, these data suggest a promising potential of domatinostat in combination with immunotherapy to improve the outcome of refractory cancer patients.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
The immune response against cancer generated by type-I-interferons (IFN-1) has recently been described. Exogenous and endogenous IFN-α/β have an important role in immune surveillance and control of tumor development. In addition, IFN-1s have recently emerged as novel DAMPs for the consecutive events connecting innate and adaptive immunity, and they also have been postulated as an essential requirement for induction of immunogenic cell death (ICD). In this context, photodynamic therapy (PDT) has been previously linked to the ICD. PDT consists in the administration of a photosensitizer (PS) and its activation by i...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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