Treatment landscape of triple-negative breast cancer — expanded options, evolving needs

Nature Reviews Clinical Oncology, Journal Year: 2021, Volume and Issue: 19(2), P. 91 - 113

Published: Nov. 9, 2021

Language: Английский

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Evolving therapeutic landscape of advanced hepatocellular carcinoma

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2022, Volume and Issue: 20(4), P. 203 - 222

Published: Nov. 11, 2022

Language: Английский

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Neuroendocrine and Adrenal Tumors, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology

Journal of the National Comprehensive Cancer Network, Journal Year: 2021, Volume and Issue: 19(7), P. 839 - 868

Published: July 1, 2021

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Neuroendocrine and Adrenal Gland Tumors focus on the diagnosis, treatment, management of patients with neuroendocrine tumors (NETs), adrenal tumors, pheochromocytomas, paragangliomas, multiple endocrine neoplasia. NETs are generally subclassified by site origin, stage, histologic characteristics. Appropriate diagnosis treatment often involves collaboration between specialists disciplines, using specific biochemical, radiologic, surgical methods. Specialists include pathologists, endocrinologists, radiologists (including nuclear medicine specialists), medical, radiation, oncologists. These guidelines discuss both sporadic hereditary intended to assist clinical decision-making. This article is focused 2021 principles genetic risk assessment counseling recommendations well-differentiated grade 3 NETs, poorly differentiated carcinomas, paragangliomas.

Language: Английский

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FDA Approval Summary: Pembrolizumab for the Treatment of Tumor Mutational Burden–High Solid Tumors

Clinical Cancer Research, Journal Year: 2021, Volume and Issue: 27(17), P. 4685 - 4689

Published: June 3, 2021

Abstract The FDA approved pembrolizumab on June 16, 2020, for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden–high [TMB-H; ≥10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior who no satisfactory alternative options. granted approval based a clinically important overall response rate (29%; 95% confidence interval, 21–39) duration (57% responses lasting ≥ 12 months) in subset TMB-H tumors (n = 102) spanning nine different types enrolled multicenter single-arm trial (KEYNOTE-158). efficacy was supported results whole-exome sequencing (WES) analyses TMB additional across multiple clinical trials, scientific understanding effects PD-1 inhibition. Overall, adverse event profile similar to observed trials other indications. This is first time has cancer indication TMB, fourth presence biomarker rather than primary site origin.

Language: Английский

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Turning cold tumors hot: from molecular mechanisms to clinical applications

Trends in Immunology, Journal Year: 2022, Volume and Issue: 43(7), P. 523 - 545

Published: May 25, 2022

Language: Английский

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Association of High Tumor Mutation Burden in Non–Small Cell Lung Cancers With Increased Immune Infiltration and Improved Clinical Outcomes of PD-L1 Blockade Across PD-L1 Expression Levels

JAMA Oncology, Journal Year: 2022, Volume and Issue: 8(8), P. 1160 - 1160

Published: June 16, 2022

Importance Although tumor mutation burden (TMB) has been explored as a potential biomarker of immunotherapy efficacy in solid tumors, there still is lack consensus about the optimal TMB threshold that best discriminates improved outcomes immune checkpoint inhibitor therapy among patients with non–small cell lung cancer (NSCLC). Objectives To determine association between increasing levels and across clinically relevant programmed death ligand–1 (PD-L1) NSCLC. Design, Setting, Participants This multicenter cohort study included advanced NSCLC treated who received death–1 (PD-1) or PD-L1 inhibition Dana-Farber Cancer Institute (DFCI), Memorial Sloan Kettering Center (MSKCC), Stand Up (SU2C)/Mark Foundation data sets. Clinicopathological genomic were collected from September 2013 2020. Data analysis was performed November 2021 to February 2022. Exposures Treatment PD-1/PD-L1 without chemotherapy. Main Outcomes Measures Association objective response rate (ORR), progression-free survival (PFS), overall (OS). Results In entire 1552 blockade, median (range) age 66 (22-92) years, 830 (53.5%) women, 1347 (86.8%) had nonsquamous histologic profile. A regression tree modeling ORR function identified 2 groupings discovery defined low (≤19.0 mutations per megabase) high (>19.0 megabase), which associated improvements ORR, PFS, OS independent cohorts (DFCI SU2C/Mark Foundation). These also significant each proportion score subgroup less than 1%, 1% 49%, 50% higher. The 57% expression higher 8.7% 1%. Multiplexed immunofluorescence transcriptomic profiling revealed increased CD8-positive, PD-L1–positive T-cell infiltration, on cells, upregulation innate adaptive signatures. Conclusions Relevance findings suggest are infiltration an inflammatory T-cell–mediated response, resulting sensitivity blockade subgroups.

Language: Английский

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Real-world application of tumor mutational burden-high (TMB-high) and microsatellite instability (MSI) confirms their utility as immunotherapy biomarkers

ESMO Open, Journal Year: 2021, Volume and Issue: 7(1), P. 100336 - 100336

Published: Dec. 23, 2021

Microsatellite instability (MSI) testing and tumor mutational burden (TMB) are genomic biomarkers used to identify patients who likely benefit from immune checkpoint inhibitors. Pembrolizumab was recently approved by the Food Drug Administration for use in TMB-high (TMB-H) tumors, regardless of histology, based on KEYNOTE-158. The primary objective this retrospective study real-world applicability immunotherapy TMB/MSI-high lend credence refine biomarker.Charts with advanced solid tumors had MSI/TMB status determined next generation sequencing (NGS) (FoundationOne CDx) were reviewed. Demographics, diagnosis, treatment history, overall response rate (ORR) abstracted. Progression-free survival (PFS) Kaplan-Meier curves. PFS1 (chemotherapy PFS) PFS2 (immunotherapy received after progressing chemotherapy. median PFS2/PFS1 ratio recorded.MSI-high or TMB-H [≥20 mutations per megabase (mut/MB)] detected 157 adults a total 27 distinct histologies. Median turnaround time NGS 73 days. ORR most recent chemotherapy 34.4%. 55.9%. PFS versus 6.75 months (95% confidence interval, 3.9-10.9 months) 24.2 9.6 not reached), respectively (P = 0.042). 4.7 favor immunotherapy.This reinforces TMB as predictive biomarker. Barriers exist timely implementation NGS-based more data needed raise awareness about clinical utility TMB. Clinicians should consider treating their histology.

Language: Английский

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Targeting the DNA damage response in immuno-oncology: developments and opportunities

Nature reviews. Cancer, Journal Year: 2021, Volume and Issue: 21(11), P. 701 - 717

Published: Aug. 10, 2021

Language: Английский

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Clinical and analytical validation of FoundationOne®CDx, a comprehensive genomic profiling assay for solid tumors

PLoS ONE, Journal Year: 2022, Volume and Issue: 17(3), P. e0264138 - e0264138

Published: March 16, 2022

FoundationOne®CDx (F1CDx) is a United States (US) Food and Drug Administration (FDA)-approved companion diagnostic test to identify patients who may benefit from treatment in accordance with the approved therapeutic product labeling for 28 drug therapies. F1CDx utilizes next-generation sequencing (NGS)-based comprehensive genomic profiling (CGP) technology examine 324 cancer genes solid tumors. reports known likely pathogenic short variants (SVs), copy number alterations (CNAs), select rearrangements, as well complex biomarkers including tumor mutational burden (TMB) microsatellite instability (MSI), addition loss of heterozygosity (gLOH) ovarian cancer. CGP services can reduce complexity biomarker testing, enabling precision medicine improve decision-making outcomes patients, but only if results are reliable, accurate, validated clinically analytically highest standard available. The analyses presented herein demonstrate extensive analytical clinical validation supporting initial subsequent FDA approvals ensure high sensitivity, specificity, reliability data reported. included several in-depth evaluations assay performance limit detection (LoD), blank (LoB), precision, orthogonal concordance SVs (including base substitutions [SUBs] insertions/deletions [INDELs]), CNAs amplifications homozygous deletions), biomarkers. >30,000 comprises considerable increasing body evidence that supports utility match tumors targeted therapies or immunotherapies based on their tumor's meets needs providers receive guideline-based helping them keep pace rapidly evolving field medicine.

Language: Английский

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Macrophages at the interface of the co-evolving cancer ecosystem

Cell, Journal Year: 2023, Volume and Issue: 186(8), P. 1627 - 1651

Published: March 15, 2023

Language: Английский

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