Clinical benefit of a precision medicine based approach for guiding treatment of refractory cancers

Milan Radovich, Patrick J. Kiel, Stacy M. Nance, Erin E. Niland, Megan E. Parsley, Meagan E. Ferguson, Guanglong Jiang, Natraj R. Ammakkanavar, Lawrence Einhorn, Liang Cheng, Mehdi Nassiri, Darrell Davidson, Daniel A. Rushing, Patrick Loehrer, Roberto Pili, Nasser Hanna, J. Thomas Callaghan, Todd Skaar, Paul Helft, Safi ShahdaBert H. O'Neil, Bryan Schneider

Research output: Contribution to journalArticle

29 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)56491-56500
Number of pages10
JournalOncotarget
Volume7
Issue number35
DOIs
StatePublished - 2016

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Precision Medicine
Disease-Free Survival
Neoplasms
Therapeutics
Standard of Care
Genomics
Fluorescence In Situ Hybridization
Immunohistochemistry
RNA

Keywords

  • Genomics
  • Next-generation sequencing
  • Personalized medicine
  • Precision medicine

ASJC Scopus subject areas

  • Oncology

Cite this

Clinical benefit of a precision medicine based approach for guiding treatment of refractory cancers. / Radovich, Milan; Kiel, Patrick J.; Nance, Stacy M.; Niland, Erin E.; Parsley, Megan E.; Ferguson, Meagan E.; Jiang, Guanglong; Ammakkanavar, Natraj R.; Einhorn, Lawrence; Cheng, Liang; Nassiri, Mehdi; Davidson, Darrell; Rushing, Daniel A.; Loehrer, Patrick; Pili, Roberto; Hanna, Nasser; Thomas Callaghan, J.; Skaar, Todd; Helft, Paul; Shahda, Safi; O'Neil, Bert H.; Schneider, Bryan.

In: Oncotarget, Vol. 7, No. 35, 2016, p. 56491-56500.

Research output: Contribution to journalArticle

Radovich, M, Kiel, PJ, Nance, SM, Niland, EE, Parsley, ME, Ferguson, ME, Jiang, G, Ammakkanavar, NR, Einhorn, L, Cheng, L, Nassiri, M, Davidson, D, Rushing, DA, Loehrer, P, Pili, R, Hanna, N, Thomas Callaghan, J, Skaar, T, Helft, P, Shahda, S, O'Neil, BH & Schneider, B 2016, 'Clinical benefit of a precision medicine based approach for guiding treatment of refractory cancers', Oncotarget, vol. 7, no. 35, pp. 56491-56500. https://doi.org/10.18632/oncotarget.10606
Radovich, Milan ; Kiel, Patrick J. ; Nance, Stacy M. ; Niland, Erin E. ; Parsley, Megan E. ; Ferguson, Meagan E. ; Jiang, Guanglong ; Ammakkanavar, Natraj R. ; Einhorn, Lawrence ; Cheng, Liang ; Nassiri, Mehdi ; Davidson, Darrell ; Rushing, Daniel A. ; Loehrer, Patrick ; Pili, Roberto ; Hanna, Nasser ; Thomas Callaghan, J. ; Skaar, Todd ; Helft, Paul ; Shahda, Safi ; O'Neil, Bert H. ; Schneider, Bryan. / Clinical benefit of a precision medicine based approach for guiding treatment of refractory cancers. In: Oncotarget. 2016 ; Vol. 7, No. 35. pp. 56491-56500.
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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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AU - Radovich, Milan

AU - Kiel, Patrick J.

AU - Nance, Stacy M.

AU - Niland, Erin E.

AU - Parsley, Megan E.

AU - Ferguson, Meagan E.

AU - Jiang, Guanglong

AU - Ammakkanavar, Natraj R.

AU - Einhorn, Lawrence

AU - Cheng, Liang

AU - Nassiri, Mehdi

AU - Davidson, Darrell

AU - Rushing, Daniel A.

AU - Loehrer, Patrick

AU - Pili, Roberto

AU - Hanna, Nasser

AU - Thomas Callaghan, J.

AU - Skaar, Todd

AU - Helft, Paul

AU - Shahda, Safi

AU - O'Neil, Bert H.

AU - Schneider, Bryan

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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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KW - Personalized medicine

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