Pilot study using molecular profiling of patients' tumors to find potential targets and select treatments for their refractory cancers

Daniel D. Von Hoff, Joseph J. Stephenson, Peter Rosen, David M. Loesch, Mitesh J Borad, Stephen Anthony, Gayle Jameson, Susan Brown, Nina Cantafio, Donald A. Richards, Tom R. Fitch, Ernesto Wasserman, Cristian Fernandez, Sylvan Green, William Sutherland, Michael Bittner, Arlet Alarcon, David Mallery, Robert Penny

Research output: Contribution to journalArticle

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Abstract

Purpose: To compare the progression-free survival (PFS) using a treatment regimen selected by molecular profiling (MP) of a patient's tumor with the PFS for the most recent regimen on which the patient had experienced progression (ie, patient as his own control). Patients and Methods: Patients with refractory metastatic cancer had tissue samples submitted for MP in two formats including formalin-fixed tissue for immunohistochemistry and fluorescent in situ hybridization assays and immediately frozen tissue for oligonucleotide microarray (MA) gene expression assays (all performed in a Clinical Laboratory Improvement Amendments [CLIA] - certified laboratory). The MP approach was deemed of clinical benefit for the individual patient who had a PFS ratio (PFS on MP-selected therapy/PFS on prior therapy) of ≥ 1.3. Results: In 86 patients who had MP attempted, there was a molecular target detected in 84 (98%). Sixty-six of the 84 patients were treated according to MP results. Eighteen (27%) of 66 patients had a PFS ratio of ≥ 1.3 (95% CI, 17% to 38%; one-sided, one-sample P = .007). Therefore, the null hypothesis (that ≤ 15% of this patient population would have a PFS ratio of ≥ 1.3) was rejected. Conclusion: It is possible to identify molecular targets in patients' tumors from nine different centers across the United States. In 27% of patients, the MP approach resulted in a longer PFS on an MP-suggested regimen than on the regimen on which the patient had just experienced progression. Issues to be considered in interpretation of this study include limited prior experience with patients as their own controls as a study end point and overall patient attrition.

Original languageEnglish (US)
Pages (from-to)4877-4883
Number of pages7
JournalJournal of Clinical Oncology
Volume28
Issue number33
DOIs
StatePublished - Nov 20 2010

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Disease-Free Survival
Neoplasms
Therapeutics
Oligonucleotide Array Sequence Analysis
Fluorescence In Situ Hybridization
Formaldehyde
Immunohistochemistry
Gene Expression
Population

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Pilot study using molecular profiling of patients' tumors to find potential targets and select treatments for their refractory cancers. / Von Hoff, Daniel D.; Stephenson, Joseph J.; Rosen, Peter; Loesch, David M.; Borad, Mitesh J; Anthony, Stephen; Jameson, Gayle; Brown, Susan; Cantafio, Nina; Richards, Donald A.; Fitch, Tom R.; Wasserman, Ernesto; Fernandez, Cristian; Green, Sylvan; Sutherland, William; Bittner, Michael; Alarcon, Arlet; Mallery, David; Penny, Robert.

In: Journal of Clinical Oncology, Vol. 28, No. 33, 20.11.2010, p. 4877-4883.

Research output: Contribution to journalArticle

Von Hoff, DD, Stephenson, JJ, Rosen, P, Loesch, DM, Borad, MJ, Anthony, S, Jameson, G, Brown, S, Cantafio, N, Richards, DA, Fitch, TR, Wasserman, E, Fernandez, C, Green, S, Sutherland, W, Bittner, M, Alarcon, A, Mallery, D & Penny, R 2010, 'Pilot study using molecular profiling of patients' tumors to find potential targets and select treatments for their refractory cancers', Journal of Clinical Oncology, vol. 28, no. 33, pp. 4877-4883. https://doi.org/10.1200/JCO.2009.26.5983
Von Hoff, Daniel D. ; Stephenson, Joseph J. ; Rosen, Peter ; Loesch, David M. ; Borad, Mitesh J ; Anthony, Stephen ; Jameson, Gayle ; Brown, Susan ; Cantafio, Nina ; Richards, Donald A. ; Fitch, Tom R. ; Wasserman, Ernesto ; Fernandez, Cristian ; Green, Sylvan ; Sutherland, William ; Bittner, Michael ; Alarcon, Arlet ; Mallery, David ; Penny, Robert. / Pilot study using molecular profiling of patients' tumors to find potential targets and select treatments for their refractory cancers. In: Journal of Clinical Oncology. 2010 ; Vol. 28, No. 33. pp. 4877-4883.
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abstract = "Purpose: To compare the progression-free survival (PFS) using a treatment regimen selected by molecular profiling (MP) of a patient's tumor with the PFS for the most recent regimen on which the patient had experienced progression (ie, patient as his own control). Patients and Methods: Patients with refractory metastatic cancer had tissue samples submitted for MP in two formats including formalin-fixed tissue for immunohistochemistry and fluorescent in situ hybridization assays and immediately frozen tissue for oligonucleotide microarray (MA) gene expression assays (all performed in a Clinical Laboratory Improvement Amendments [CLIA] - certified laboratory). The MP approach was deemed of clinical benefit for the individual patient who had a PFS ratio (PFS on MP-selected therapy/PFS on prior therapy) of ≥ 1.3. Results: In 86 patients who had MP attempted, there was a molecular target detected in 84 (98{\%}). Sixty-six of the 84 patients were treated according to MP results. Eighteen (27{\%}) of 66 patients had a PFS ratio of ≥ 1.3 (95{\%} CI, 17{\%} to 38{\%}; one-sided, one-sample P = .007). Therefore, the null hypothesis (that ≤ 15{\%} of this patient population would have a PFS ratio of ≥ 1.3) was rejected. Conclusion: It is possible to identify molecular targets in patients' tumors from nine different centers across the United States. In 27{\%} of patients, the MP approach resulted in a longer PFS on an MP-suggested regimen than on the regimen on which the patient had just experienced progression. Issues to be considered in interpretation of this study include limited prior experience with patients as their own controls as a study end point and overall patient attrition.",
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T1 - Pilot study using molecular profiling of patients' tumors to find potential targets and select treatments for their refractory cancers

AU - Von Hoff, Daniel D.

AU - Stephenson, Joseph J.

AU - Rosen, Peter

AU - Loesch, David M.

AU - Borad, Mitesh J

AU - Anthony, Stephen

AU - Jameson, Gayle

AU - Brown, Susan

AU - Cantafio, Nina

AU - Richards, Donald A.

AU - Fitch, Tom R.

AU - Wasserman, Ernesto

AU - Fernandez, Cristian

AU - Green, Sylvan

AU - Sutherland, William

AU - Bittner, Michael

AU - Alarcon, Arlet

AU - Mallery, David

AU - Penny, Robert

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N2 - Purpose: To compare the progression-free survival (PFS) using a treatment regimen selected by molecular profiling (MP) of a patient's tumor with the PFS for the most recent regimen on which the patient had experienced progression (ie, patient as his own control). Patients and Methods: Patients with refractory metastatic cancer had tissue samples submitted for MP in two formats including formalin-fixed tissue for immunohistochemistry and fluorescent in situ hybridization assays and immediately frozen tissue for oligonucleotide microarray (MA) gene expression assays (all performed in a Clinical Laboratory Improvement Amendments [CLIA] - certified laboratory). The MP approach was deemed of clinical benefit for the individual patient who had a PFS ratio (PFS on MP-selected therapy/PFS on prior therapy) of ≥ 1.3. Results: In 86 patients who had MP attempted, there was a molecular target detected in 84 (98%). Sixty-six of the 84 patients were treated according to MP results. Eighteen (27%) of 66 patients had a PFS ratio of ≥ 1.3 (95% CI, 17% to 38%; one-sided, one-sample P = .007). Therefore, the null hypothesis (that ≤ 15% of this patient population would have a PFS ratio of ≥ 1.3) was rejected. Conclusion: It is possible to identify molecular targets in patients' tumors from nine different centers across the United States. In 27% of patients, the MP approach resulted in a longer PFS on an MP-suggested regimen than on the regimen on which the patient had just experienced progression. Issues to be considered in interpretation of this study include limited prior experience with patients as their own controls as a study end point and overall patient attrition.

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