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

Mapping Intimacies ◽

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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Advanced melanoma, a pharmacological evaluation

European Journal of Public Health ◽

10.1093/eurpub/ckab120.091 ◽

2021 ◽

Vol 31 (Supplement_2) ◽

Author(s):

Anabela Andrade ◽

Jorge Balteiro

Keyword(s):

Overall Survival ◽

Targeted Therapy ◽

Braf Inhibitor ◽

Progression Free Survival ◽

Mek Inhibitor ◽

Advanced Melanoma ◽

New Drugs ◽

High Rate ◽

Free Survival ◽

Dismal Prognosis

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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Progression and hyperprogression after anti-PD1 therapy for unresectable stage III or IV melanoma patients.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e21021 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e21021-e21021

Author(s):

Elise Colle ◽

Stéphane Dalle ◽

Laurent Mortier ◽

Bernard Guillot ◽

Caroline Dutriaux ◽

...

Keyword(s):

Survival Rates ◽

Real Life ◽

Advanced Melanoma ◽

First Line ◽

Best Response ◽

Unresectable Stage ◽

Group A ◽

Similar Survival ◽

Group B ◽

Response Group

e21021 Background: Primary progression (PP) and secondary progression (SP) to anti-PD1 therapy (APD) are poorly described in advanced melanoma in real life practice. Hyperprogression with a deleterious effect is reported in many cancers but is poorly assessed in advanced melanoma. Methods: Characteristics of 793 patients treated by APD (nivolumab or pembrolizumab) between July 2014 and May 2018 were collected from MelBase, a prospective French biobank (NCT02828202).We considered: group A (progressive disease as best response), group AHP (hyperprogression) within group A patients (progression/death within 3 months with normal initial LDH and ECOG at baseline, and either ECOG increased from 0 to 3-4, either LDH increased from normal to elevated or both), group B SP (response or stable disease then progression). Characteristics for all and survival for patients alive at progression (AAP) were also described. Results: Median follow-up was 11.3 months (Q1-Q3 4.8–23.6). Characteristics at baseline are in the table. In group A, 14% patients died at progression; within 262 patients AAP, 17% continue APD (the same or switch), 15.1% (CI95 11.1-20.6) were alive 1-year after progression (1YAP); 20.5% for patients in first line and 11.5% for pretreated. In group AHP, 41% patients died at progression; within 48 patients AAP, 12% continue APD, 11.1% (CI95 7.8-13.6) were alive 1YAP. In group B, 11% patients died at progression; within 88 patients AAP, 36% continue APD, 10.3% (CI95 5.2-20.1) were alive 1YAP, 15.9% for patients in first line and 7.0% for pre-treated. Conclusions: Our study shows that PP and SP to APD differ at baseline, but have similar survival rates at progression, while mechanisms involved might be different, providing important landmarks to build second line trials. This study thus highlights the existence of hyperprogressors among which 41% patients died within 3 months, as well as describes their associated characteristics. [Table: see text]

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Role of Dermatologists in Advanced Cutaneous Melanoma Treatment: A Call for Action (Preprint)

10.2196/preprints.29915 ◽

2021 ◽

Author(s):

Louay Samir Abdulkarim

Keyword(s):

Adverse Events ◽

Health Care Professionals ◽

Cutaneous Melanoma ◽

Detrimental Effect ◽

Survival Rates ◽

Melanoma Treatment ◽

Melanoma Patients ◽

The Impact ◽

Fragmentation Of Care

UNSTRUCTURED Advanced cutaneous melanoma has always been a dreaded diagnosis, but with the introduction of a number of practice-changing agents, namely targeted therapy and immunotherapy, considerable strides have been achieved in terms of survival rates. However, the introduction of these agents was associated with a variety of dermatological adverse event, some of which have shown a detrimental effect on the continuity of treatment. This holds especially true in the light of the current fragmentation of care provided by the managing health care professionals. This article sheds light on the impact of the scarcity of dermatology specialist input in the management of dermatological adverse events associated with advanced melanoma treatment. Furthermore, it looks into the potential avenues where dermatological input can bridge the gap in the care provided by oncologists, hence standardising the care provided to melanoma patients with dermatological adverse events.

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Changeable Conditional Survival Rates and Associated Prognosticators in Patients with Metastatic Renal Cell Carcinoma Receiving First Line Targeted Therapy

The Journal of Urology ◽

10.1016/j.juro.2018.06.030 ◽

2018 ◽

Vol 200 (5) ◽

pp. 989-995 ◽

Cited By ~ 4

Author(s):

Minyong Kang ◽

Jae Young Park ◽

Chang Wook Jeong ◽

Eu Chang Hwang ◽

Cheryn Song ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Targeted Therapy ◽

Cell Carcinoma ◽

Metastatic Renal Cell Carcinoma ◽

Renal Cell ◽

Survival Rates ◽

Conditional Survival ◽

First Line

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Outcomes of patients with sarcomatoid renal cell carcinoma: The Mayo Clinic experience.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.6_suppl.359 ◽

2013 ◽

Vol 31 (6_suppl) ◽

pp. 359-359 ◽

Cited By ~ 2

Author(s):

Brian Addis Costello ◽

Ben Zhang ◽

Christine M. Lohse ◽

Stephen A. Boorjian ◽

John Cheville ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Targeted Therapy ◽

Survival Rate ◽

Survival Rates ◽

Distant Metastases ◽

First Line ◽

Cancer Specific Survival ◽

Time Of Surgery ◽

Sarcomatoid Renal Cell Carcinoma ◽

One Year

359 Background: Sarcomatoid renal cell carcinoma (RCC) is an aggressive form of RCC and is associated with a poor prognosis. Standard therapies tend to be less effective in this subset of patients. Methods: Using the Mayo Clinic Nephrectomy Registry, 206 patients with sarcomatoid RCC treated with partial or radical nephrectomy were identified. These patients were characterized based on extent of disease, treatment response and survival. Results: Of these 206, there was no evidence of distant metastases in 110 patients at the time of surgery and the estimated distant metastases-free survival at one year was 44%. The estimated cancer-specific survival rate at one and five years was 56% and 20%, respectively. Compared to patients with grade 4 RCC without sarcomatoid features, those with sarcomatoid RCC were more likely to develop distant metastases following surgery (hazard ratio 1.49). Considering those with metastatic sarcomatoid RCC, 96 patients had metastases at the time of surgery and 77 with no metastases at the time of surgery subsequently developed distant metastases (n=173). Of these, 156 died at a mean of 1.0 years from time of first evidence of distant metastases with a median cancer-specific survival of 0.6 years. Estimated cancer-specific survival rates from time of first metastases at one year and five years were 34% and 4%, respectively. The most common metastatic sites: lung (46%), bone (15%), liver (13%), non-regional lymph nodes (9%), and brain (5%). Patients who received targeted systemic therapy (10%) with either sunitinib (n=14), sorafenib (2) or pazopanib (1) for their first occurrence of distant metastases had an estimated cancer-specific survival rate at one year of 69%, compared to 30% for patients who did not. Median cancer-specific survival for those receiving targeted therapy as first-line was 2.2 years compared to 0.6 years for those patients who did not. Conclusions: Sarcomatoid RCC is an aggressive subtype of kidney cancer as evidenced by poor survival rates. The patients in this registry with metastatic sarcomatoid RCC who received targeted therapy as first-line treatment had improved cancer-specific survival rates.

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

Current Oncology ◽

10.3390/curroncol28050338 ◽

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.

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