Precision Medicine in the Treatment of Melanoma

Aderhold, Kimberly; Wilson, Melissa A.; Berger, Adam C.; Levi, Shoshana T.; Bennett, Joseph

doi:10.1016/j.soc.2019.08.001

Cited by 6 publications

(4 citation statements)

References 49 publications

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“…While PIK3CA alterations occur in 36% or more of breast cancer patients [ 38 ] there are other relevant biomarkers to consider in these patients, including ERBB2 , BRCA1 , BRCA2 , NTRK , and MSI (or mismatch repair deficiency) [ 13 ]. Furthermore, targetable alterations ae increasingly being identified across numerous other solid tumor types, including non-small cell lung cancer [ 39 ], prostate cancer [ 40 ], colorectal and other gastrointestinal malignancies [ 41 ], ovarian cancer [ 42 ], melanoma [ 43 ], and others. The studies herein describe the ability to interrogate and identify alterations in these relevant genes in a single assay, providing pertinent genomic information from a single, minimally invasive molecular test.…”

Section: Discussionmentioning

confidence: 99%

Clinical and analytical validation of FoundationOne Liquid CDx, a novel 324-Gene cfDNA-based comprehensive genomic profiling assay for cancers of solid tumor origin

Woodhouse¹,

Hughes³

et al. 2020

PLoS ONE

275

221

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As availability of precision therapies expands, a well-validated circulating cell-free DNA (cfDNA)-based comprehensive genomic profiling assay has the potential to provide considerable value as a complement to tissue-based testing to ensure potentially life-extending therapies are administered to patients most likely to benefit. Additional data supporting the clinical validity of cfDNA-based testing is necessary to inform optimal use of these assays in the clinic. The FoundationOne ® Liquid CDx assay is a pan-cancer cfDNA-based comprehensive genomic profiling assay that was recently approved by FDA. Validation studies included >7,500 tests and >30,000 unique variants across >300 genes and >30 cancer types. Clinical validity results across multiple tumor types are presented. Additionally, results demonstrated a 95% limit of detection of 0.40% variant allele fraction for select substitutions and insertions/deletions, 0.37% variant allele fraction for select rearrangements, 21.7% tumor fraction for copy number amplifications, and 30.4% TF for copy number losses. The limit of detection for microsatellite instability and blood tumor mutational burden were also determined. The false positive variant rate was 0.013% (approximately 1 in 8,000). Reproducibility of variant calling was 99.59%. In comparison with an orthogonal method, an overall positive percent agreement of 96.3% and negative percent agreement of >99.9% was observed. These study results demonstrate that FoundationOne Liquid CDx accurately and reproducibly detects the major types of genomic alterations in addition to complex biomarkers such as microsatellite instability, blood tumor mutational burden, and tumor fraction. Critically, clinical validity data is presented across multiple cancer types.

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Section: Discussionmentioning

confidence: 99%

Clinical and analytical validation of FoundationOne Liquid CDx, a novel 324-Gene cfDNA-based comprehensive genomic profiling assay for cancers of solid tumor origin

Woodhouse¹,

Hughes³

et al. 2020

PLoS ONE

275

221

View full text Add to dashboard Cite

show abstract

“…M olecular characterization of tumors and the patient genome, referred to as precision oncology, has revolutionized the treatment and management of many cancers. [1][2][3] Gynecologic oncology is undergoing one such paradigm shift. The advent of poly-ADP ribose polymerase inhibitors changed the management of primary and recurrent ovarian cancer.…”

mentioning

confidence: 99%

Enrollment of Individuals From Racial and Ethnic Minority Groups in Gynecologic Cancer Precision Oncology Trials

Mattei

Robb

Banning

et al. 2022

Obstetrics &Amp; Gynecology

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To characterize whether enrollment patterns in precision oncology clinical trials for gynecologic cancers reflect the racial and ethnic diversity of patients with gynecologic cancers in the United States. METHODS:ClinicalTrials.gov was queried to perform this cross-sectional review. We included precision oncology trials-defined as trials using molecular profiling of a tumor or the patient genome to identify targetable alterations to guide treatment-of ovarian, uterine, cervical, and vulvar cancers in the United States. National Cancer Institute Surveillance, Epidemiology, and End Results and United States Census Bureau data were used to estimate cancer burden and the expected number of trial participants by race and ethnicity for each gynecologic cancer. The ratio of actual-to-expected participants was calculated. A ratio greater than 1 signified overenrollment. A random effects meta-analysis was performed to assess the relative weights of individual trials. RESULTS:We identified 493 trials, 61 of which met inclusion criteria. There were 2,573 patients enrolled in ovarian cancer trials, 1,197 in uterine cancer trials and 162 in cervical cancer trials. Non-Hispanic White women were overrepresented overall (enrollment ratio 1.26, 95% CI 1.20-1.32) and across all cancer types on subgroup analysis. Asian women, non-Hispanic Black women, and Hispanic women were underrepresented overall (enrollment ratios 0.63, 95% CI 0.41-0.86; 0.51, 95% CI 0.36-0.66 and 0.30, 95% CI 0.23-0.36, respectively). In subgroup analyses, Asian women and non-Hispanic Black women were underrepresented in ovarian and uterine cancer trials and Hispanic women were underrepresented across all cancer types. CONCLUSION: Non-Hispanic Black women, Asian women, and Hispanic women with gynecologic cancers are underrepresented in precision oncology trials. Few U.S.-based precision oncology trials exist for uterine and cervical cancers, which have a high burden of morbidity and mortality among racial and ethnic minority groups. Failure to equitably enroll patients who belong to racial and ethnic minority groups may perpetuate existing disparities in gynecologic cancer outcomes.

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“…26 While the advent of immunotherapies targeting the programmed death-1 (PD-1) and programmed death-1 ligand (PDL-1) has revolutionized the treatment of advanced and metastatic melanoma, unfortunately these agents are largely contraindicated in organ transplant recipients due to the risk of inciting graft rejection. 27 However, there are multiple case reports describing the successful use of immune checkpoint inhibitors for advanced and metastatic melanoma in organ transplant recipients in which patients demonstrated clinical response to therapy and the graft function was preserved including reports of ipilimumab monotherapy and ipilimumab followed by nivolumab in renal transplant recipients 28,29 as well as reports of ipilimumab and pembrolizumab monotherapy in liver transplant recipients. 30,31 Merkel's Cell Carcinoma and Kaposi's Sarcoma Solid-organ transplant recipients have also been shown to be at increased risk of developing both Merkel's cell carcinoma (MCC) and Kaposi's sarcoma (KS), both of which have an underlying viral pattern of carcinogenesis.…”

Section: Melanomamentioning

confidence: 99%

Skin Cancers and Lung Transplant

Wilken

Carucci

Stevenson

2021

Semin Respir Crit Care Med

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It is well known that solid-organ transplant recipients (SOTRs) have a 65- to 100-fold increase in the risk of developing skin cancer, namely, nonmelanoma skin cancers (NMSCs) such as cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC). In addition, these patients are also at increased risk for development of melanoma as well as other less common cutaneous malignancies (Merkel's cell carcinoma, Kaposi's sarcoma). SOTRs with NMSC (namely cSCC) are also at significantly increased risk of poor clinical outcomes including local recurrence, nodal and distant metastasis, and disease-specific death relative to patients who are not immunosuppressed. Increased surveillance and monitoring in patients at risk of aggressive disease and poor outcomes who are on immunosuppression is essential in patients with lung transplants given the high degree of immunosuppression. Increased awareness of risks, treatments, and management allows for improved outcomes in these patients. This article will provide an overview of the risk factors for the development of cutaneous malignancies in organ transplant recipients as well as a detailed discussion of various immunosuppressant and prophylactic medications used in this patient population that contribute to the risk of developing cutaneous malignancies, with an emphasis on NMSC (cSCC and BCC) in lung transplant recipients. Finally, this article includes a discussion on the clinical and dermatologic management of this high-risk immunosuppressed population including a review of topical and systemic agents for field therapy of actinic damage and chemoprevention of keratinocyte carcinomas. In addition, indications for additional treatment and preventive measures such as adjuvant radiation treatment after surgical management of cutaneous malignancies and potential modification of immunosuppressive medication regimens are discussed.

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Precision Medicine in the Treatment of Melanoma

Cited by 6 publications

References 49 publications

Clinical and analytical validation of FoundationOne Liquid CDx, a novel 324-Gene cfDNA-based comprehensive genomic profiling assay for cancers of solid tumor origin

Clinical and analytical validation of FoundationOne Liquid CDx, a novel 324-Gene cfDNA-based comprehensive genomic profiling assay for cancers of solid tumor origin

Enrollment of Individuals From Racial and Ethnic Minority Groups in Gynecologic Cancer Precision Oncology Trials

Skin Cancers and Lung Transplant

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