4.7 Article

Case series of outcomes in advanced cancer patients with single pathway alterations receiving N-of-One therapies

Journal

NPJ PRECISION ONCOLOGY
Volume 6, Issue 1, Pages -

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41698-022-00259-7

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Funding

  1. Joan and Irwin Jacobs Fund
  2. National Cancer Institute [P30 CA023100]
  3. NIH [K08CA168999, R21CA192072]
  4. Pedal the Cause
  5. David Foundation
  6. Kristen Ann Carr Fund

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This study evaluated the impact of N-of-One therapeutic strategies on the outcome of patients with only one genomic alteration or alterations in one oncogenic pathway. The results showed that a subset of cancer patients may benefit from customized therapeutic matching.
Though advanced cancers generally display complex molecular portfolios, there is a subset of patients whose malignancies possess only one genomic alteration or alterations in one oncogenic pathway. We assess how N-of-One therapeutic strategies impact outcomes in these patients. From 12/2012 to 9/2018, 429 therapy-evaluable patients with diverse treatment-refractory cancers were presented at Molecular Tumor Boards at Moores Cancer Center at UC San Diego. The clinical benefit rate, defined by RECIST1.1, was assessed for patients with solid tumors who underwent next-generation sequencing (NGS) profiling revealing one genomic or pathway alteration, subsequently managed with N-of-One therapies. Nine of 429 patients (2.1%) met evaluation criteria. Using matched therapy indicated by NGS, the clinical benefit rate (stable disease 6 months/partial/complete response) was 66.7%. Median progression-free survival was 11.3 months (95% CI: 3.4-not evaluable). Thus, a small subset of diverse cancers has single pathway alterations on NGS testing. These patients may benefit from customized therapeutic matching.

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