scholarly journals Combined ipilimumab and nivolumab first‐line and after BRAF‐targeted therapy in advanced melanoma

2019 ◽  
Vol 33 (2) ◽  
pp. 358-365 ◽  
Author(s):  
Robert Mason ◽  
Helen C. Dearden ◽  
Bella Nguyen ◽  
Jennifer A. Soon ◽  
Jessica Louise Smith ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Advanced Melanoma ◽  
First Line

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

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.

scholarly journals Real World Outcomes in Patients with Advanced Melanoma Treated in Alberta, Canada: A Time-Era Based Analysis

2021 ◽  
Vol 28 (5) ◽  
pp. 3978-3986
Author(s):  
Rodrigo Rigo ◽  
Jordan Doherty ◽  
Kim Koczka ◽  
Shiying Kong ◽  
Philip Q. Ding ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Map Kinase ◽  
Real World ◽  
Immune Checkpoint ◽  
Single Agent ◽  
Advanced Melanoma ◽  
First Line ◽  
Term Survival ◽  
Map Kinase Pathway ◽  
Kinase Pathway

Immune checkpoint and MAP kinase pathway inhibitors can significantly improve long-term survival for patients with melanoma. There is limited real-world data of these regimens’ effectiveness. We retrospectively analyzed 402 patients with unresectable and metastatic melanoma between August 2013 and July 2020 treated with immune checkpoint inhibitors and MAP kinase pathway targeted therapy in Alberta, Canada. Overall survival (OS) was compared using Kaplan–Meier and Cox regression analyses. Subgroup survival outcomes were analyzed by first-line treatment regime and BRAF mutation status. Three treatment eras were defined based on drug access: prior to August 2013, August 2013 to November 2016, and November 2016 to July 2020. Across each era, there were improvements in median OS: 11.7 months, 15.9 months, and 33.6 months, respectively. Patients with BRAF mutant melanoma had improved median OS when they were treated with immunotherapy in the first line as opposed to targeted therapy (median OS not reached for immunotherapy versus 17.4 months with targeted treatment). Patients with BRAF wild-type melanomas had improved survival with ipilimumab and nivolumab versus those treated with a single-agent PD-1 inhibitor (median OS not reached and 21.2 months). Our real-world analysis confirms significant survival improvements with each subsequent introduction of novel therapies for advanced melanoma.

scholarly journals Switching first-line targeted therapy after not reaching low disease activity within 6 months is superior to conservative approach: a propensity score-matched analysis from the ATTRA registry

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Lucie Nekvindová ◽  
Jiří Vencovský ◽  
Karel Pavelka ◽  
Pavel Horák ◽  
Zlatuše Křístková ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Targeted Therapy ◽  
Propensity Score ◽  
Disease Activity ◽  
Treatment Response ◽  
Daily Clinical Practice ◽  
Current Therapy ◽  
First Line ◽  
Treatment Target ◽  
Low Disease Activity

Abstract Background Treat-to-target (T2T) is a widely accepted strategy for patients with rheumatoid arthritis (RA). It recommends attaining a goal of at least low disease activity (LDA) within 6 months; otherwise, the current therapy should be modified. We aimed to investigate whether switching a first-line targeted therapy (TT) in patients not reaching LDA within 6 months leads to a higher probability of meeting LDA at the 12-month visit in daily clinical practice using data from Czech registry ATTRA. Methods We included patients with RA starting the first-line TT from 1 January 2012 to 31 January 2017 with at least 1-year follow-up. We created four mutually exclusive cohorts based on (1) switching to another TT within the first year and (2) reaching a treatment target (DAS28-ESR ≤ 3.2) at the 6-month visit. The primary outcome was the comparison of odds for reaching remission (REM) or LDA at the 12-month visit between patients switching and not switching TT after not reaching treatment target at 6 months. Before using logistic regression to estimate the odds ratio, we employed the propensity score to match patients at the 6-month visit. Results A total of 1275 patients were eligible for the analysis. Sixty-two patients switched within the first 5 months of the treatment before evaluating treatment response at the 6-month visit (C1); 598 patients reached the treatment target within 6 months of therapy (C2); 124 patients did not reach treatment response at 6-month visit and switched to another therapy (C3), and 491 patients continued with the same treatment despite not reaching LDA at the 6-month visit (C4). We matched 75 patients from cohort C3 and 75 patients from C4 using the propensity score. Patients following the T2T principle (C3) showed 2.8 (95% CI 1.4–5.8; p = 0.005) times increased likelihood of achieving REM/LDA at the 12-month visit compared to patients not following the T2T strategy (C4). Conclusions In daily clinical practice, the application of the T2T strategy is underused. Switching TT after not reaching REM/LDA within the first 6 months leads to a higher probability of achieving REM/LDA in RA patients at the 12-month visit.

scholarly journals Real-world Outcomes of First-line Anti-PD-1 Therapy for Advanced Melanoma: A Nationwide Population-based Study

2020 ◽  
Vol 43 (8) ◽  
pp. 256-264
Author(s):  
Michiel C.T. van Zeijl ◽  
John B.A.G. Haanen ◽  
Michel W.J.M. Wouters ◽  
Liesbeth C. de Wreede ◽  
Anouk Jochems ◽  
...  
Keyword(s):  
Real World ◽  
Population Based ◽  
Advanced Melanoma ◽  
First Line ◽  
Population Based Study

scholarly journals A systematic review and network meta-analysis of immunotherapy and targeted therapy for advanced melanoma

2017 ◽  
Vol 6 (6) ◽  
pp. 1143-1153 ◽  
Author(s):  
Joao Paulo da Silveira Nogueira Lima ◽  
Mina Georgieva ◽  
Benjamin Haaland ◽  
Gilberto de Lima Lopes
Keyword(s):  
Systematic Review ◽  
Targeted Therapy ◽  
Meta Analysis ◽  
Advanced Melanoma
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