Publications by authors named "Schilsky R"
Optimizing public private partnerships to support clinical cancer research.
J Natl Cancer Inst
December 2024
Public-private partnerships (PPPs) in cancer research have emerged as a pivotal model in the development of strategies to rapidly advance therapeutic innovations. The collaboration between public entities, such as government agencies and research institutions, and private entities, including pharmaceutical and biotechnology companies, as well as nonprofit organizations, brings together diverse expertise, resources, and perspectives to address the challenges of efficient drug development and equitable care delivery. This synergy has the potential to accelerate the translation of basic research findings into tangible clinical applications.
View Article and Find Full Text PDFBackground: Dysregulated pathways in cancer may be hub addicted. Identifying these dysregulated networks for targeting might lead to novel therapeutic options.
Objective: Considering the hypothesis that central hubs are associated with increased lethality, identifying key hub targets within central networks could lead to the development of novel drugs with improved efficacy in advanced metastatic solid tumors.
Article Synopsis
- The study evaluated the effectiveness of palbociclib, a targeted cancer therapy, in patients with advanced cancer exhibiting specific genomic alterations, focusing on two patient groups: those with head and neck cancer (HNC) and those with a mix of histologies (HP).
- Results showed that 40% of the HNC patients achieved disease control, which was statistically significant, while only 13% of the HP cohort did, failing to meet the criteria for significance.
- The treatment had notable side effects, with over 40% of patients experiencing serious adverse events, primarily blood-related issues like neutropenia and thrombocytopenia.
Purpose: Targeted Agent and Profiling Utilization Registry (TAPUR) is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations known to be drug targets. Results of a cohort of patients with soft tissue sarcoma with cyclin-dependent kinase 4 () amplification treated with palbociclib are reported.
Methods: Eligible patients had measurable disease, Eastern Cooperative Oncology Group performance status 0 to 2, adequate organ function, and no standard treatment options.
Article Synopsis
- A study conducted at Dana-Farber/Boston Children's Cancer and Blood Disorders Center focused on classifying pediatric solid tumor diagnoses and analyzing genomic mutations to improve clinical trial design and treatment options.
- Over 6.5 years, the research included 888 pediatric cancer patients, revealing that 33% had genomic variants that aligned with precision oncology trials, while 14% received targeted therapies.
- The findings stress the significance of using genomic data for enhancing treatment strategies and the necessity for data sharing, particularly for addressing rare pediatric cancers in clinical settings.
Purpose: The Targeted Agent and Profiling Utilization Registry Study is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations known to be drug targets. Results of a cohort of patients with various solid tumors with germline or somatic mutations treated with talazoparib are reported.
Methods: Eligible patients had advanced solid tumors, measurable disease (RECIST), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options.
Background: POLE and POLD1 proofreading deficiency (POLE/D1pd) define a rare subtype of ultramutated metastatic colorectal cancer (mCRC; over 100 mut/Mb). Disease-specific data about the activity and efficacy of immune checkpoint inhibitors (ICIs) in POLE/D1pd mCRC are lacking and it is unknown whether outcomes may be different from mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) mCRCs treated with ICIs.
Patients And Methods: In this global study, we collected 27 patients with mCRC harboring POLE/D1 mutations leading to proofreading deficiency and treated with anti-programmed cell death-ligand 1 alone +/- anti-cytotoxic T-lymphocyte antigen-4 agents.
Article Synopsis
- The study evaluates the effectiveness of targeted agents, specifically pertuzumab plus trastuzumab, in patients with advanced biliary tract cancer (BTC) who have specific genomic alterations.
- Out of 29 enrolled patients, the treatment showed a 40% disease control rate, with some experiencing significant responses, indicating potential benefits of this combination therapy.
- Although the treatment was generally well-received, a few patients reported notable adverse events, highlighting the importance of monitoring safety alongside treatment efficacy.
Purpose: Targeted Agent and Profiling Utilization Registry is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer with genomic alterations known to be drug targets. Results of a cohort of patients with solid tumors with alterations treated with regorafenib are reported.
Methods: Eligible patients had measurable disease (RECIST v.
Purpose: With the advent of precision medicine, molecular tumor boards (MTBs) were established to interpret genomic results and guide decision making for targeted therapy in oncology patients. There are currently no universal guidelines for how MTBs should operate and thus variance can be seen depending on which MTB is reviewing the case. This study assesses the concordance of MTB recommendations when a participant case is reviewed by two different MTBs, establishes potential reasons for discordance, and advocates for the establishment of standard MTB operating guidelines.
View Article and Find Full Text PDFPurpose: The Targeted Agent and Profiling Utilization Registry Study is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations known to be drug targets. Results from cohorts of patients with metastatic breast cancer (BC) with and alterations treated with sunitinib are reported.
Methods: Eligible patients had measurable disease, Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options.
The global pharmaceutical industry portfolio is skewed towards cancer and rare diseases due to more predictable development pathways and financial incentives. In contrast, drug development for major chronic health conditions that are responsible for a large part of mortality and disability worldwide is stalled. To examine the processes of novel drug development for common chronic health conditions, a multistakeholder Think Tank meeting, including thought leaders from academia, clinical practice, non-profit healthcare organizations, the pharmaceutical industry, the Food and Drug Administration (FDA), payors as well as investors, was convened in July 2022.
View Article and Find Full Text PDFPurpose: The Targeted Agent and Profiling Utilization Registry Study is a phase II basket study evaluating antitumor activity of commercially available targeted agents in patients with advanced cancers with genomic alterations known to be drug targets. The results in a cohort of patients with solid tumors with mutations treated with cobimetinib plus vemurafenib are reported.
Methods: Eligible patients had measurable disease (RECIST v.
Purpose: The Targeted Agent and Profiling Utilization Registry Study is a phase II basket study evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancers with genomic alterations known to be drug targets. Results of a cohort of patients with solid tumors with mutations treated with nivolumab plus ipilimumab are reported.
Methods: Eligible patients had measurable disease (RECIST v.
Article Synopsis
- The TAPUR Study evaluates the effectiveness of approved targeted agents, specifically pembrolizumab, in treating patients with advanced cancers that have specific genomic alterations, focusing on those with high tumor mutational burden (HTMB).
- The study included 77 patients with advanced colorectal cancer (CRC) and other cancers, assessing outcomes like disease control and overall response rates; results showed a disease control rate of 31% for CRC and 45% for the pooled cohort.
- It concluded that pembrolizumab is effective in demonstrating antitumor activity in patients who have already undergone treatment for advanced cancers with HTMB, although some patients experienced serious adverse effects.
The conceptual framework of pragmatism in clinical trials is explored using the American Society of Clinical Oncology's pragmatic, non-randomized, phase II, multi-center basket clinical trial, the Targeted Agent and Profiling Utilization Registry Study (NCT02693535) as a model. The Targeted Agent and Profiling Utilization Registry Study aims to identify signals of drug activity when Food and Drug Administration approved drugs are matched to pre-specified genomic targets in patients with advanced cancer outside of their approved indication(s). The objectives of the study are to generate evidence of potential signals of activity in targeted therapies prescribed in an off-label setting as well as to expose and educate community cancer centers to genomic testing and precision medicine through the study protocol.
View Article and Find Full Text PDFArticle Synopsis
- The Targeted Agent and Profiling Utilization Registry Study is testing the effectiveness of targeted treatments for advanced lung cancer patients with specific genomic alterations.
- The study involved 28 patients, primarily with non-small-cell lung cancer, who received a combination therapy of pertuzumab and trastuzumab, aiming for disease control and measuring various outcomes, including overall survival.
- Results indicated a 37% disease control rate, with some patients showing a partial response, though there were also notable serious side effects from the treatment.
Purpose: CancerLinQ seeks to use data sharing technology to improve quality of care, improve health outcomes, and advance evidence-based research. Understanding the experiences and concerns of patients is vital to ensure its trustworthiness and success.
Methods: In a survey of 1,200 patients receiving care in four CancerLinQ-participating practices, we evaluated awareness and attitudes regarding participation in data sharing.
Purpose: The TAPUR Study is a pragmatic basket trial evaluating antitumor activity of commercially available targeted agents in patients with advanced cancers harboring potentially actionable genomic alterations. Data from a cohort of patients with endometrial cancer (EC) with or amplification, overexpression, or mutation treated with pertuzumab plus trastuzumab (P + T) are reported.
Methods: Eligible patients had advanced EC, no standard treatment options, measurable disease (RECIST v1.
Background: The current model of clinical drug development in oncology displays major limitations due to a high attrition rate in patient enrollment in early phase trials and a high failure rate of drugs in phase III studies.
Objective: Integrating transcriptomics for selection of patients has the potential to achieve enhanced speed and efficacy of precision oncology trials for any targeted therapies or immunotherapies.
Methods: Relative gene expression level in the metastasis and normal organ-matched tissues from the WINTHER database was used to estimate the potential clinical benefit of specific treatments in a variety of metastatic solid tumors.
Article Synopsis
- The TAPUR Study is a phase II trial that tests the effectiveness of targeted therapies, specifically olaparib, in patients with advanced prostate cancer and specific genomic mutations.
- 30 patients with metastatic castrate-resistant prostate cancer were treated with olaparib, resulting in a 69% disease control rate and a 58% objective response rate, alongside median radiographic progression-free survival of 38.4 weeks and overall survival of 76.4 weeks.
- The study suggests that olaparib shows promising antitumor activity for patients with these mutations, indicating a need for further research to incorporate it into standard treatments.
Purpose: TAPUR is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations known to be drug targets. The results of a cohort of patients with colorectal cancer (CRC) with mutations treated with cobimetinib (C) plus vemurafenib (V) are reported.
Methods: Eligible patients had advanced CRC, no standard treatment options, measurable disease (RECIST), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, tumors with V600E/D/K/R mutations, and no , , or mutations.
Background: SARS-CoV-2 (COVID-19) elicits a T-cell antigen-mediated immune response of variable efficacy. To understand this variability, we explored transcriptomic expression of angiotensin-converting enzyme 2 (, the SARS-CoV-2 receptor) and of immunoregulatory genes in normal lung tissues from patients with non-small cell lung cancer (NSCLC).
Methods: This study used the transcriptomic and the clinical data for NSCLC patients generated during the CHEMORES study [ = 123 primary resected (early-stage) NSCLC] and the WINTHER clinical trial ( = 32 metastatic NSCLC).