BRAF, NRAS and C-KIT Advanced Melanoma: Clinico-pathological Features, Targeted-Therapy Strategies and Survival

Abstract Background Cutaneous melanoma is an aggressive cancer that occurs in melanocytes, located in the epidermis. Historically it has a high rate of morbidity and mortality, due to the resistance and toxicity of traditional therapies. Its incidence has increased annually by 4% to 8%. Until 2011 it was still considered a devastating and almost always fatal disease in a few months. Advances in therapies have significantly improved the results of most patients with advanced melanoma, especially those with a BRAFV600 mutation, which account for almost 50% of tumors. Before the recent evolution in treatment, the prognosis and overall survival were considered very bad. The introduction of new drugs has improved progression-free survival and overall survival, as well as producing faster clinical responses. Methods Comparison of endpoints such as progression-free survival and overall melanoma survival from the Summary of Product Characteristics (SPC) studies of each drug in the therapeutic groups under assessment used in the disease. The variables used were the Endpoints Global Survival at various times (12 months, 24 months, 36 months and the median) and Progression-Free Survival. Results Combined immunotherapy (Nivolumab and Ipilimumab) improves overall survival and progression-free survival, achieving better results than targeted therapy. In this, the combination of a BRAF inhibitor and a MEK inhibitor, presents better results with the combination of Encorafenib and Binimetinib. Conclusions Both targeted therapy and immunotherapy transform melanoma with a dismal prognosis into a life-threatening illness.

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A Longitudinal Analysis of IDO and PDL1 Expression during Immune- or Targeted Therapy in Advanced Melanoma

Neoplasia ◽

10.1016/j.neo.2017.12.002 ◽

2018 ◽

Vol 20 (2) ◽

pp. 218-225 ◽

Cited By ~ 13

Author(s):

Lukas Krähenbühl ◽

Simone M Goldinger ◽

Joanna Mangana ◽

Katrin Kerl ◽

Ines Chevolet ◽

...

Keyword(s):

Targeted Therapy ◽

Longitudinal Analysis ◽

Advanced Melanoma

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Chemotherapeutic, Immunologic, and Molecularly Targeted Therapy for the Treatment of Advanced Melanoma

Frontiers in Clinical Drug Research - Anti-Cancer Agents ◽

10.2174/9781681082899116030005 ◽

2016 ◽

pp. 217-270

Author(s):

Said C. Azoury ◽

David M. Straughan ◽

Robert D. Bennett ◽

Vivek Shukla

Keyword(s):

Targeted Therapy ◽

Advanced Melanoma ◽

Molecularly Targeted Therapy

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Multiple Chemotherapy-Based Combination Therapy Strategies for Advanced Lung Cancer Patients: A Systematic Review and Network Meta-Analysis

10.20944/preprints202005.0478.v1 ◽

2020 ◽

Author(s):

Lecai Xiong ◽

Yuquan Bai ◽

Xuefeng Zhou ◽

Ming Xu ◽

Gaofeng Pan ◽

...

Keyword(s):

Lung Cancer ◽

Targeted Therapy ◽

Combination Therapy ◽

Meta Analysis ◽

Objective Response ◽

Advanced Lung Cancer ◽

Combination Therapies ◽

Outcome Indicators ◽

Therapeutic Benefits ◽

Therapy Strategies

Background: At present, the treatments for patients with advanced lung cancer focus on chemotherapy, targeted therapy, immunotherapy, or a combination of multiple treatments. Purpose: The main purpose of this study is to compare the various chemotherapy-based combination therapies and find the best one for patients with advanced lung cancer. Methods: Based on database (PubMed, EMBASE and Medline) for randomized controlled trials of advanced lung cancer with combination therapy from 2008 to 2020, we searched literatures with overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and adverse as outcome indicators and established a Bayesian mesh meta-analysis for multiple treatment strategies. Then, we combined the results of four outcome indicators to find out the best chemotherapy-based combination therapy strategy for patients with advanced lung cancer, further, we tried to screen out the best drugs of which were commonly used now. Results: It contained a total of 51 studies, including five combination therapies: Chemotherapy/Chemotherapy plus placebo (CT), chemotherapy plus one targeted therapy drug (CT+T), chemotherapy plus two targeted therapy drugs (CT+T+T), chemotherapy combined with immunotherapy (CT+I) or chemotherapy combined with biotherapy (CT+B). In terms of four outcome indicators, CT+I showed the best therapeutic benefits. In the comparison of immunotherapy drugs, pembrolizumab showed the best effect. Conclusion: Our results showed that, among the multiple chemotherapy-based combination therapy strategies, chemotherapy combined with immunotherapy is the best choice for patients with advanced lung cancer, and pembrolizumab combined with chemotherapy has the best effect.

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Clinicopathologic Relevance of Claudin 18.2 Expression in Gastric Cancer: A Meta-Analysis

Frontiers in Oncology ◽

10.3389/fonc.2021.643872 ◽

2021 ◽

Vol 11 ◽

Author(s):

Bogdan Silviu Ungureanu ◽

Cristian-Virgil Lungulescu ◽

Daniel Pirici ◽

Adina Turcu-Stiolica ◽

Dan Ionut Gheonea ◽

...

Keyword(s):

Gastric Cancer ◽

Overall Survival ◽

Targeted Therapy ◽

Odds Ratio ◽

Web Of Science ◽

Meta Analysis ◽

Pathological Features ◽

Potential Efficacy ◽

The Relationship ◽

Review Manager

An increasing number of tumor markers have been discovered to have potential efficacy as diagnostic and prognostic tools in gastric cancer. We aimed to assess putative correlations between claudin 18.2 expression and pathological or prognosis features in patients with gastric cancer. MEDLINE, Web of Science, EBSCO, and ClinicalTrials.gov were used to search for relevant studies from their inception to 30 October 2020. Finally, a total of six articles were included in this meta-analysis. Review Manager 5 software was applied to examine the heterogeneity among the studies and to calculate the odds ratio with 95% CI by selecting corresponding models, in evaluating the strength of the relationship. Publication bias test was also conducted. No bias and no significant correlations were found between CLDN 18.2 and TNM stages, Lauren classification, HER2, grading, or overall survival. This meta-analysis expounded that the relationship with CLDN 18.2 and pathological features depends on the percentage of staining of tumor cells for which CLDN 18.2 is considered positive. Our pooled outcomes suggest that targeted therapy for CLDN 18.2 could be effective if certain criteria were established.

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Mechanisms of resistance to BRAF and MEK inhibitors and clinical update of US Food and Drug Administration-approved targeted therapy in advanced melanoma

OncoTargets and Therapy ◽

10.2147/ott.s182721 ◽

2018 ◽

Vol Volume 11 ◽

pp. 7095-7107 ◽

Cited By ~ 64

Author(s):

Sunilkumar Kakadia ◽

Naveen Yarlagadda ◽

Ramez Awad ◽

Madappa Kundranda ◽

Jiaxin Niu ◽

...

Keyword(s):

Targeted Therapy ◽

Drug Administration ◽

Food And Drug Administration ◽

Advanced Melanoma ◽

Mechanisms Of Resistance ◽

Mek Inhibitors

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Genetic Profiling of Advanced Melanoma: Candidate Mutations for Predicting Sensitivity and Resistance to Targeted Therapy

Targeted Oncology ◽

10.1007/s11523-020-00695-0 ◽

2020 ◽

Vol 15 (1) ◽

pp. 101-113 ◽

Cited By ~ 4

Author(s):

Magdalena Olbryt ◽

Wojciech Pigłowski ◽

Marcin Rajczykowski ◽

Aleksandra Pfeifer ◽

Sebastian Student ◽

...

Keyword(s):

Targeted Therapy ◽

Advanced Melanoma ◽

Genetic Profiling

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Combined BRAF-Targeted Therapy with Immunotherapy in BRAF-Mutated Advanced Melanoma Patients

Current Oncology Reports ◽

10.1007/s11912-021-01134-7 ◽

2021 ◽

Vol 23 (12) ◽

Author(s):

Pier Francesco Ferrucci ◽

Marko Lens ◽

Emilia Cocorocchio

Keyword(s):

Targeted Therapy ◽

Advanced Melanoma ◽

Melanoma Patients

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First-line Advanced Cutaneous Melanoma Treatments: Where Do We Stand? (Preprint)

10.2196/preprints.29912 ◽

2021 ◽

Author(s):

Louay Samir Abdulkarim

Keyword(s):

Targeted Therapy ◽

Cutaneous Melanoma ◽

Specific Immunotherapy ◽

Survival Rates ◽

Mek Inhibitor ◽

Advanced Melanoma ◽

First Line ◽

Growth And Survival ◽

Clear Cut ◽

Melanoma Treatment

UNSTRUCTURED Cutaneous melanoma has always been a dreaded diagnosis due to its high mortality rate and its proclivity for invasiveness and metastasis. Historically, advanced melanoma treatment was limited to chemotherapy and nonspecific immunotherapy agents that displayed poor curative potential and high toxicity. However, during the last decade, the evolving understanding of the mutational burden of melanoma and the immune system evasion mechanisms has led to the development of targeted therapy and specific immunotherapy agents that have transformed the landscape of advanced melanoma treatment. Targeted therapy comprises of agents that directly inhibit mutated kinases, namely BRAF and MEK, which have been implicated in the growth and survival of cancerous melanocytes. However, the efficacy of BRAF and MEK inhibitor monotherapies was limited by early resistance and an upsurge in treatment-associated skin tumours. Consequently, a combined BRAF/MEK inhibitor approach was trialled, which resulted in superior survival rates while minimising the aforementioned limitations. On the other hand, specific immunotherapy agents were developed on the heels of Nobel Prize-winning discoveries that outlined the pivotal role of certain immune downregulatory signals that facilitate tumour growth. Despite the considerable strides in understanding the clinical implication of these agents, there is a scarcity in randomised clinical trials that directly compare the efficacy of the aforementioned agents, hence there are no clear-cut preferences among the available first-line options. This paper attempts to summarise the current understanding of first-line treatments. Additionally, it describes the indirect comparative evidence that aids in bridging the gap in the literature.

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