The impact of patient characteristics and disease-specific factors on first-line treatment decisions for BRAF-mutated melanoma: results from a European expert panel study

Ascierto, Paolo A.; Bastholt, Lars; Ferrucci, Pier Francesco; Hansson, Johan; Rodas, Iván Márquez; Payne, Miranda; Robert, Caroline; Thomas, Luc; Utikal, Jochen; Wolter, Pascal; Kudlac, Amber; Tuson, Harriet; McKendrick, Jan

doi:10.1097/cmr.0000000000000455

Cited by 13 publications

(10 citation statements)

References 7 publications

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“…A number of mechanisms have been proposed for cross‐resistance to ICB post‐TT 43 . Clinicians often have to balance the propensity for a rapid but brief metabolic shutdown with TT 44,45 compared to a slower acting but potentially more durable benefit with ICB when selecting therapy for melanoma. It is important to note that there is currently a lack of randomised data comparing the sequencing of ICB vs TT approaches 46 …”

Section: Effect On Clinical Practicementioning

confidence: 99%

Immune checkpoint blockade in solid organ tumours: Choice, dose and predictors of response

Navani

Graves

Westhuizen

2020

Brit J Clinical Pharma

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Immune checkpoint blockade has transformed outcomes across solid organ tumours. Monoclonal antibodies targeting the negative inhibitory cytotoxic T lymphocyte‐associated protein 4 and programmed‐death 1/programmed death‐ligand 1 axis can lead to deep and durable responses across several tumour streams in the advanced setting. This immunotherapy approach is increasingly used earlier in the treatment paradigm. A rapidly evolving regulatory, reimbursement and drug development landscape has accompanied this novel class of immunotherapy. Unfortunately, only a small proportion of patients respond meaningfully to these agents. Here we review how the underlying tumoural genomic, histological and immunological characteristics interact within various patient phenotypes, leading to variations in response to checkpoint blockade. Concurrently, we outline the clinical trial and real‐world evidence that allows for appropriate selection of agent, dose and schedule in solid organ malignancies. An exploration of current trends in basic and translational research in immune checkpoint blockade accompanies a commentary on future clinical directions for checkpoint blockade in oncology.

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Section: Effect On Clinical Practicementioning

confidence: 99%

Immune checkpoint blockade in solid organ tumours: Choice, dose and predictors of response

Navani

Graves

Westhuizen

2020

Brit J Clinical Pharma

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“…In parallel, immunotherapies (inhibitors of CTLA4, PD1 and PDL1) have shown very interesting results, since some treated patients have not presented any relapse to date 7 . Unfortunately, no test can identify potentially responders and these therapies are not free of toxicity 8 . Finally, association between targeted therapies and immunotherapies confers a longer progression-free survival and duration of response, but led to a higher rate of serious toxicity 9 .…”

Section: Introductionmentioning

confidence: 99%

Imidazopyridine-fused [1,3]diazepinones: modulations of positions 2 to 4 and their impacts on the anti-melanoma activity

Baccon-Sollier

Malki

Maye

et al. 2020

Journal of Enzyme Inhibition and Medicinal Chemistry

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A series of 19 novel pyrido-imidazodiazepinones, with modulations of positions 2, 3 and 4 of the diazepine ring were synthesised and screened for their in vitro cytotoxic activities against two melanoma cell lines (A375 and MDA-MB-435) and for their potential toxicity against NIH-3T3 non-cancerous cells. Selected compounds were also evaluated on the NCI-60 cell line panel. The SAR study revealed that the molecular volume and the cLogP of compounds modified at position 2 were significantly correlated with the activity of these compounds on melanoma cell lines. Moreover, introduction of a heterocyclic group at position 2 or an azido-alkyl chain at position 4 led to compounds displaying a significantly different activity profile on the NCI-60 cell line panel, compared to phenyl-substituted compounds at position 2 of the diazepinone. This study provides us crucial information for the development of new derivatives active against melanoma.

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“…1,[5][6][7] The high number of approved drugs for the treatment of melanoma in the past decade has brought increased complexity to the clinical decisionmaking process, yet limited information is available regarding physician preferences on how to treat the disease. 8 Our aim in this publication is to report the results of a proprietary survey of physicians that treat advanced/ metastatic melanoma patients in the USA and WE, conducted in 2019, to better understand their current treatment practices in light of the changing market landscape.…”

Section: Introductionmentioning

confidence: 99%

“… 1 , 5 - 7 The high number of approved drugs for the treatment of melanoma in the past decade has brought increased complexity to the clinical decision-making process, yet limited information is available regarding physician preferences on how to treat the disease. 8 …”

Section: Introductionmentioning

confidence: 99%

<p>Treatment of Advanced/Metastatic Melanoma in the United States and Western Europe: Results of the CancerMPact Survey</p>

Hawthorne

Zhao

Hanson

et al. 2020

CMAR

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Context: Melanoma treatment has substantially changed over the last several years, yet little information regarding physician's preferences around treatment exists. Objective: Our aim is to describe the results of the CancerMPact (CMP) survey performed in 2019 about the treatment of advanced/metastatic melanoma. Methods: CMP is a data source from Kantar, Health Division, containing data on cancer epidemiology and treatment. Once a year, Kantar performs a series of surveys with specialists in the field of interest in the United States of America (USA), Western Europe (WE), Japan, and China. The results of the survey reported in this work comprise the answers from 94 USA and 99 WE physicians about the treatment of melanoma. Results: In the first-line for the BRAF wild-type population, immuno-oncology (IO) drugs including nivolumab, ipilimumab or pembrolizumab (alone or in combination) were used in 80.1% of the cases in the USA and 70.6% in WE. Conventional chemotherapy or cytokinebased treatments were used in 16.4% of the USA patients and 28.2% in WE. In the secondline in the USA, 45.8% of BRAF wild-type patients received IO drugs, while 45.0% of patients received conventional chemotherapy or cytokine-based treatments. The majority of patients with BRAF mutant advanced/metastatic melanoma were treated in the first-line with BRAF-targeted therapy (61.3% USA, 71.9% WE), and few patients received conventional chemotherapy or cytokine-based treatments (11.9% USA, 12.4% WE); the most commonly used BRAF-targeted therapy was the combination of dabrafenib plus trametinib. In the second-line, BRAF mutant patients received IO drugs (45.1% USA, 53.7% WE), targeted therapy (37.6% USA, 32% WE) or conventional chemotherapy/cytokine-based treatments (14.4% USA, 11.7% WE). Conclusion: The use of IO or targeted therapy for patients with advanced/metastatic melanoma is the preferred treatment strategy by physicians in the USA and WE based on BRAF mutation status. Many patients still receive conventional chemotherapies or cytokines with unsubstantial benefit, especially in recurrent patients of BRAF wild type.

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The impact of patient characteristics and disease-specific factors on first-line treatment decisions for BRAF-mutated melanoma: results from a European expert panel study

Abstract: Supplemental Digital Content is available in the text.

Cited by 13 publications

References 7 publications

Immune checkpoint blockade in solid organ tumours: Choice, dose and predictors of response

Immune checkpoint blockade in solid organ tumours: Choice, dose and predictors of response

Imidazopyridine-fused [1,3]diazepinones: modulations of positions 2 to 4 and their impacts on the anti-melanoma activity

<p>Treatment of Advanced/Metastatic Melanoma in the United States and Western Europe: Results of the CancerMPact Survey</p>

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