Delays in Pediatric Evaluation of New and Relevant Cancer Therapies

The genomic revolution has advanced our understanding of the biology of cancer, highlighting potentially promising approaches to target tumors that blur the conventional lines defined by organ-based, and often age-based, malignancies. For example, effective BRAF V600E targeting with RAF and MEK inhibitors is not limited to melanoma, but rather numerous adult and pediatric cancers driven by this ubiquitous oncogene. [1] Adashek J.J. Menta A.K. Reddy N.K. Desai A.P. Roszik J. Subbiah V. Tissue-Agnostic Activity of BRAF plus MEK Inhibitor in BRAF V600-Mutant Tumors. Mol Cancer Ther. 2022; 21: 871-878 Crossref PubMed Scopus (17) Google Scholar Recent studies involving ultra-selective kinase inhibitors, such as those targeting aberrations in TRK or RET, are leveraging basket trial schemas to explore pan-cancer assessments and secure histology-agnostic, and in some cases age-agnostic Food and Drug Administration (FDA) approvals. [2] Drilon A. Laetsch T.W. Kummar S. DuBois S.G. Lassen U.N. Demetri G.D. et al. Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children. N Engl J Med. 2018; 378: 731-739 Crossref PubMed Scopus (1764) Google Scholar ,[3] Subbiah V. Wolf J. Konda B. Kang H. Spira A. Weiss J. et al. Tumour-agnostic efficacy and safety of selpercatinib in patients with RET fusion-positive solid tumours other than lung or thyroid tumours (LIBRETTO-001): a phase 1/2, open-label, basket trial. Lancet Oncol. 2022; 23: 1261-1273 Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar While we laud efforts to improve our precision with targeting cancer, drug development and early phase clinical trials evaluating novel agents in children remain susceptible to inequity. Timing for First-in-Minor Clinical Trials of New Cancer DrugsThe Journal of PediatricsVol. 263PreviewTo describe the delay for first-in-minor cancer clinical trials and its relationship with the Food and Drug Administration (FDA) approval. Full-Text PDF