4.4 Article

Initiative for Molecular Profiling and Advanced Cancer Therapy (IMPACT): An MD Anderson Precision Medicine Study

Journal

JCO PRECISION ONCOLOGY
Volume 1, Issue -, Pages -

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1200/PO.17.00002

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Funding

  1. Alberto Barretto donor fund
  2. Jamie Hope donor fund
  3. Institute for Personalized Cancer Therapy
  4. National Institutes of Health/National Cancer Institute [P30 CA016672]
  5. NATIONAL CANCER INSTITUTE [P30CA016672] Funding Source: NIH RePORTER

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Purpose Genomic profiling is increasingly used in the management of cancer. We have previously reported preliminary results of our precision medicine program. Here, we present response and survival outcomes for 637 additional patients who were referred for phase I trials and were treated with matched targeted therapy (MTT) when available. Patients and Methods Patients with advanced cancer who underwent tumor genomic analyses were treated with MTT when available. Results Overall, 1,179 (82.1%) of 1,436 patients had one or more alterations (median age, 59.7 years; men, 41.2%); 637 had one or more actionable aberrations and were treated with MTT (n=390) or non-MTT(n=247). Patients who were treated with MTT hadhigher rates of complete and partial response (11% v5%; P=.0099), longer failure-free survival (FFS; 3.4 v 2.9 months; P=.0015), and longer overall survival (OS; 8.4 v 7.3 months; P=.041) than did unmatched patients. Two-month landmark analyses showed that, for MTT patients, FFS for responders versus nonresponders was 7.6 versus 4.3 months (P<.001) and OS was 23.4 versus 8.5 months (P<.001), whereas for non MTT patients (responders v nonresponders), FFS was 6.6 versus 4.1 months (P=.001) and OS was 15.2 versus 7.5 months (P=.43). Patients with phosphatidylinositol 3-kinase (PI3K) andmitogen-activated protein kinase pathway alterations matched to PI3K/Akt/mammalian target of rapamycin axis inhibitors alone demonstrated outcomes comparable to unmatched patients. Conclusion Our results support the use of genomic matching. Subset analyses indicate that matching patients who harbor a PI3K and mitogen-activated protein kinase pathway alteration to only a PI3K pathway inhibitor does not improve outcome. We have initiated IMPACT2, a randomized trial to compare treatment with and without genomic selection. (C) 2017 by American Society of Clinical Oncology

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