A comparison of safety and efficacy of cytotoxic versus molecularly targeted drugs in pediatric phase I solid tumor oncology trials

Dorris, Kathleen; Liu, Chunyan; Li, Dandan; Hummel, Trent R.; Wang, Xia; Perentesis, John P.; Kim, Miok; Fouladi, Maryam

doi:10.1002/pbc.26258

Cited by 14 publications

(3 citation statements)

References 147 publications

(176 reference statements)

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“…A review of the literature suggests that in addition to its possibilities as a curative agent, targeted therapies can be less toxic than their cytotoxic counterparts. Two recent meta-analyses of phase I pediatric clinical trials showed that dose-limiting toxicity was found to be higher in cytotoxic therapies than in targeted drugs 19,20. Though our study was not designed to compare outcome or survival, we observed the application of targeted therapeutics among 12 patients and followed their outcome along with toxicities, if any.…”

Section: Discussionmentioning

confidence: 99%

“…Two recent meta-analyses of phase I pediatric clinical trials showed that dose-limiting toxicity was found to be higher in cytotoxic therapies than in targeted drugs. 19,20 Though our study was not designed to compare outcome or survival, we observed the application of targeted therapeutics among 12 patients and followed their outcome along with toxicities, if any. We noted that of our 12 patients who received targeted therapy, 2 patients experienced drug-related adverse effects leading to discontinuation of therapy.…”

Section: Discussionmentioning

confidence: 99%

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Lessons Learned: Utilization of a Reference Laboratory for Targeted Sequencing of Pediatric Tumors at a Single Institution

Swilling

Pham

Wang³

et al. 2022

Journal of Pediatric Hematology/Oncology

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Our study aims to report the prevalence of potentially actionable oncogenic variants in a sample of pediatric tumors from a single institution using a reference laboratory for tumor profiling. We investigated genomic alterations and immunotherapy biomarkers such a tumor mutation burden, microsatellite instability, and programmed death-ligand 1. Patients treated in the Cook Children’s Health Care System who had tumor profiling performed by Foundation Medicine between January 1, 2013, and May 1, 2019, were included. Demographic variables, results of tumor profiling, and subsequent use of targeted therapies were captured. Eighty-one patients were in our final data set; patients had diagnoses of central nervous system tumors (n=5), leukemia and lymphoma (n=4), neuroblastoma (n=32), and other solid tumors (n=40). One or more genomic alterations were identified in 68 (84%) of patients, 34 of which had potential targeted therapies available. In all, 44/51 patients tested for tumor mutation burden had low tumor burden, and the rest had intermediate burden. All 41 patients tested for microsatellite instability status were microsatellite stable. Six of 34 patients tested for programmed death-ligand 1 status were positive. Twelve patients received targeted therapy. This study highlights a subset of pediatric tumors harboring targetable genetic alterations and describes the use of a reference laboratory for tumor profiling.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Lessons Learned: Utilization of a Reference Laboratory for Targeted Sequencing of Pediatric Tumors at a Single Institution

Swilling

Pham

Wang³

et al. 2022

Journal of Pediatric Hematology/Oncology

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“…From each study, we extracted data related to: study characteristics (e.g., year of results publication, phase, funding, study status), patient characteristics (e.g., age, number of adverse events (AEs) and response rates of anticancer agents in phase I adults as well as pediatric clinical trials [16][17][18][19][20]; others focused on the risks and benefits of particular drugs [21,22] or interventions in specific cancer types [23,24]. Historically, targeted drugs are considered to have a better toxicity profile than chemotherapy agents [25,26].…”

Section: Data Extractionmentioning

confidence: 99%

Risk and Benefit for Targeted Therapy Agents in Pediatric Phase II Trials in Oncology: A Systematic Review with a Meta-Analysis

et al. 2021

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Background For research with human participants to be ethical, risk must be in a favorable balance with potential benefits. Little is known about the risk/benefit ratio for pediatric cancer phase II trials testing targeted therapies. Objective Our aim was to conduct a systematic review of preliminary efficacy and safety profiles of phase II targeted therapy clinical trials in pediatric oncology. Methods Our protocol was prospectively registered in PROSPERO (CRD42020146491). We searched EMBASE and Pub-Med for phase II pediatric cancer trials testing targeted agents. We included solid and hematological malignancy studies published between 1 January, 2015 and 27 February, 2020. We measured risk using drug-related grade 3 or higher adverse events, and benefit by response rates. When possible, data were meta-analyzed. All statistical tests were two-sided. Results We identified 34 clinical trials (1202 patients) that met our eligibility criteria. The pooled overall response rate was 24.4% (95% confidence interval [CI] 14.5-34.2) and was lower in solid tumors, 6.4% (95% CI 3.2-9.6), compared with hematological malignancies, 55.1% (95% CI 35.9-74.3); p < 0.001. The overall fatal drug-related (grade 5) adverse event rate was 1.6% (95% CI 0.6-2.5), and the average drug-related grade 3/4 adverse event rate per person was 0.66 (95% CI 0.55-0.78). Conclusions We provide an estimate for the risks and benefits of participation in pediatric phase II cancer trials. These data may be used as an empirical basis for informed communication about benefits and burdens in pediatric oncology research.

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A Comparative Study of Longitudinal Toxicities of Cytotoxic Drugs, Molecularly Targeted Agents, Immunomodulatory Drugs, and Cancer Vaccines

Hirakawa

Sudo²,

Yonemori

et al. 2019

Clin Pharma and Therapeutics

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Little is known about the toxicity of various therapeutics for cancer over time because randomized controlled clinical trials that compare several treatments are limited. In this study, we focused on the toxicities most frequently discussed, which are investigations (lab abnormalities), gastrointestinal disorders, skin and subcutaneous tissue disorders, and cardiac disorders, and compared their longitudinal toxicity data among four types of cancer therapeutics. In total, 28,235 patients who were enrolled into 772 early‐phase trials to evaluate the monotherapies of cytotoxic drugs, molecularly targeted agents, immunomodulatory drugs, or cancer vaccines were evaluated. For each toxicity, we compared their grade prevalence, mean grade at each cycle, and time to toxicity occurrence and identified the potential underlying similarities and differences of longitudinal toxicities among the four cancer treatment types. Our results will further help in understanding the profile of cancer therapeutic toxicities and their impact on oncology treatment in practice.

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A comparison of safety and efficacy of cytotoxic versus molecularly targeted drugs in pediatric phase I solid tumor oncology trials

Cited by 14 publications

References 147 publications

Lessons Learned: Utilization of a Reference Laboratory for Targeted Sequencing of Pediatric Tumors at a Single Institution

Lessons Learned: Utilization of a Reference Laboratory for Targeted Sequencing of Pediatric Tumors at a Single Institution

Risk and Benefit for Targeted Therapy Agents in Pediatric Phase II Trials in Oncology: A Systematic Review with a Meta-Analysis

A Comparative Study of Longitudinal Toxicities of Cytotoxic Drugs, Molecularly Targeted Agents, Immunomodulatory Drugs, and Cancer Vaccines

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