Clinical benefit of a precision medicine based approach for guiding treatment of refractory cancers
Open accessAbstract
// Milan Radovich 1,2,* , Patrick J. Kiel 1,2,* , Stacy M. Nance 1 , Erin E. Niland 1 , Megan E. Parsley 1 , Meagan E. Ferguson 1 , Guanglong Jiang 2 , Natraj R. Ammakkanavar 2 , Lawrence H. Einhorn 2 , Liang Cheng 2 , Mehdi Nassiri 2 , Darrell D. Davidson 2 , Daniel A. Rushing 2 , Patrick J. Loehrer 2 , Roberto Pili 2 , Nasser Hanna 2 , J. Thomas Callaghan 2 , Todd C. Skaar 2 , Paul R. Helft 2 , Safi Shahda 2 , Bert H. O’Neil 2 and Bryan P. Schneider 1,2 1 Indiana University Health Precision Genomics Program, Indianapolis, IN, USA 2 Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA * These authors have contributed equally to this work Correspondence to: Bryan P. Schneider, email: // Keywords : precision medicine, personalized medicine, genomics, next-generation sequencing Received : June 07, 2016 Accepted : June 09, 2016 Published : July 15, 2016 Abstract Patients and Methods: Patients with metastatic solid tumors who had progressed on at least one line of standard of care therapy were referred to the Indiana University Health Precision Genomics Program. Tumor samples were submitted for DNA & RNA next-generation sequencing, fluorescence in situ hybridization, and immunohistochemistry for actionable targets. A multi-disciplinary tumor board reviewed all results. For each patient, the ratio of progression-free survival (PFS) of the genomically guided line of therapy divided by the PFS of their prior line was calculated. Patients whose PFS ratio was ≥ 1.3 were deemed to have a meaningful improvement in PFS. Results: From April 2014–October 2015, 168 patients were evaluated and 101 patients achieved adequate clinical follow-up for analysis. 19 of 44 (43.2%) patients treated with genomically guided therapy attained a PFS ratio ≥ 1.3 vs . 3 of 57 (5.3%) treated with non-genomically guided therapy ( p < 0.0001). Similarly, overall PFS ratios (irrespective of cutoff) were higher for patients with genomically guided therapy vs non-genomically guided therapy ( p = 0.05). Further, patients treated with genomically guided therapy had a superior median PFS compared to those treated with non-genomically guided therapy (86 days vs . 49 days, p = 0.005, H.R. = 0.55, 95% C.I.:0.37-0.84). Conclusion: Patients with refractory metastatic cancer who receive genomically guided therapy have improved PFS ratios and longer median PFS compared to patients who do not receive genomically guided therapy.
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- Authors
- Radovich, M., Kiel, P. J., Nance, S. M., Niland, E. E., Parsley, M. E., Ferguson, M. E., Jiang, G., Ammakkanavar, N. R., Einhorn, L. H., Cheng, L., Nassiri, M., Davidson, D. D., Rushing, D. A., Loehrer, P. J., Pili, R., Hanna, N., Callaghan, J. T., Skaar, T. C., Helft, P. R., Shahda, S., O’Neil, B. H., & Schneider, B. P.
- Affiliations
- Indiana University Health (US)
- Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA
- Corresponding author
- Radovich, Milan
- Kiel, Patrick J.
- ORCID
- Venue
- Oncotarget
- Publisher
- Impact Journals, LLC
- Published
- 2016-07-15
- Volume
- 7
- Issue
- 35
- Pages
- 56491-56500
- ISSN
- 1949-2553 (ISSN-L)
- PMC
- PMC5302930
- OpenAlex
- W2464234320
- Cited by
- 111
- References
- 28
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 11 · 2023: 9 · 2022: 11 · 2021: 11 · 2020: 15 · 2019: 11 · 2018: 11 · 2017: 13 · 2016: 2
- FWCI
- 5.14
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by
- Locations
- Oncotarget (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- IUScholarWorks (Indiana University) (submittedVersion, cc-by)
- Funders
- Walther Cancer Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Keywords
- precision medicine, refractory cancer, metastatic solid tumors, progression-free survival, actionable targets, next-generation sequencing, clinical benefit, targeted therapy, multidisciplinary cancer care, treatment selection decision-making, cost-effectiveness, quality of life, patient-reported outcomes, overall survival
- MeSH terms
- Aged, Antineoplastic Combined Chemotherapy Protocols, Breast Neoplasms, Female, Humans, Immunohistochemistry, Indiana, Male, Medical Oncology, Middle Aged, Neoplasm Metastasis, Neoplasms, Pancreatic Neoplasms, Research Design, Sarcoma, Soft Tissue Neoplasms, Universities, Colorectal Neoplasms, Treatment Outcome, In Situ Hybridization, Fluorescence, Disease-Free Survival, Genomics, Precision Medicine, High-Throughput Nucleotide Sequencing
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