Multicenter analysis of genomically targeted single patient use requests for pediatric neoplasms Journal Article

   


Authors: Sabnis, H. S.; Shulman, D. S.; Mizukawa, B.; Bouvier, N.; Zehir, A.; Fangusaro, J.; Fabrizio, V. A.; Whitlow, C.; Winchester, M.; Agresta, L.; Turpin, B.; Wechsler, D. S.; DuBois, S. G.; Glade-Bender, J.; Castellino, S. M.; Shukla, N.
Article Title: Multicenter analysis of genomically targeted single patient use requests for pediatric neoplasms
Abstract: PURPOSE: The US Food and Drug Administration-expanded access program (EAP) uses a single patient use (SPU) mechanism to provide patient access to investigational agents in situations where no satisfactory or comparable therapy is available. Genomic profiling of de novo and relapsed or refractory childhood cancer has led to increased identification of new drug targets in the last decade. The aim of this study is to examine the SPU experience for genomically targeted therapies in patients with pediatric cancer. PATIENTS AND METHODS: All genomically targeted therapeutic SPUs obtained over a 5-year period were evaluated at four large pediatric cancer programs. Data were collected on the type of neoplasm, agents requested, corresponding molecularly informed targets, and clinical outcomes. RESULTS: A total of 45 SPUs in 44 patients were identified. Requests were predominantly made for CNS and solid tumors (84.4%) compared with hematologic malignancies (15.6%). Lack of an available clinical trial was the main reason for SPU initiation (64.4%). The median time from US Food and Drug Administration submission to approval was 3 days (range, 0-12 days) and from Institutional Review Board submission to approval was 5 days (range, 0-50 days). Objective tumor response was seen in 39.5% (15 of 38) of all evaluable SPUs. Disease progression was the primary reason for discontinuation of drug (66.7%) followed by toxicity (13.3%). CONCLUSION: SPU requests remain an important mechanism for pediatric access to genomically targeted agents given the limited availability of targeted clinical trials for children with high-risk neoplasms. Furthermore, this subset of SPUs resulted in a substantial number of objective tumor responses. The development of a multi-institutional data registry of SPUs may enable systematic review of toxicity and clinical outcomes and provide evidence-based access to new drugs in rare pediatric cancers.
Keywords: adolescent; adult; child; preschool child; child, preschool; young adult; genetics; clinical trial; neoplasm; neoplasms; infant; infant, newborn; multicenter study; newborn; genomics; procedures; humans; human; male; female
Journal Title: Journal of Clinical Oncology
Volume: 39
Issue: 34
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2021-12-01
Start Page: 3822
End Page: 3828
Language: English
DOI: 10.1200/jco.21.01213
PUBMED: 34591650
PROVIDER: scopus
PMCID: PMC9851705
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85122166516&doi=10.1200%2fJCO.21.01213&partnerID=40&md5=7cb63efc7405feb9c243e76d9b8388c1
Notes: Article -- Export Date: 1 February 2022 -- Source: Scopus
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MSK Authors
  1. Ahmet Zehir
    343 Zehir
  2. Nancy Bouvier
    70 Bouvier
  3. Neerav Shukla
    159 Shukla
  4. Marilyn Winchester
    3 Winchester
  5. Julia L Glade Bender
    85 Glade Bender
  6. Vanessa A Fabrizio
    16 Fabrizio
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