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Cancer therapy directed by comprehensive genomic profiling: a single center study

Published on Jul 1, 2016in Cancer Research8.38
· DOI :10.1158/0008-5472.CAN-15-3043
Jennifer J. Wheler32
Estimated H-index: 32
(University of Texas MD Anderson Cancer Center),
Filip Janku41
Estimated H-index: 41
+ 16 AuthorsRazelle Kurzrock99
Estimated H-index: 99
(UCSD: University of California, San Diego)
Abstract
Innovative molecular diagnostics deployed in the clinic enable new ways to stratify patients into appropriate treatment regimens. These approaches may resolve a major challenge for early-phase clinical trials, which is to recruit patients who, while having failed previous treatments, may nevertheless respond to molecularly-targeted drugs. We report the findings of a prospective, single-center study conducted in patients with diverse refractory cancers who underwent comprehensive genomic profiling (CGP; next-generation sequencing, 236 genes). Of the 500 patients enrolled, 188 (37.6%) received either matched (N=122/188, 65%) or unmatched therapy (N=66/188, 35%). The most common reasons that patients were not evaluable for treatment included insufficient tissue, death, or hospice transfer. The median number of molecular alterations per patient was five (range, 1-14); median number of prior therapies, four. The most common diagnoses were ovarian cancer (18%), breast cancer (16%), sarcoma (13%), and renal cancer (7%). Of the 339 successfully-profiled patients, 317 (93.5%) had at least one potentially actionable alteration. By calculating matching scores, based on the number of drug matches and genomic aberrations per patient, we found that high scores were independently associated with a greater frequency of stable disease {greater than or equal to}6 months/partial/complete remission (22% (high scores) vs. 9% (low scores), p=0.024), longer time-to-treatment failure (hazard ratio [HR]=0.52, 95% confidence interval [CI]=0.36-0.74, p=0.0003), and survival (HR=0.65, CI=0.43-1.0, p=0.05). Collectively, this study offers a clinical proof of concept for the utility of CGP in assigning therapy to patients with refractory malignancies, especially in those patients with multiple genomic aberrations for whom combination therapies could be implemented.
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  • References (54)
  • Citations (71)
References54
Newest
#1Vladimir Lazar (University of Paris-Sud)H-Index: 46
#2Eitan Rubin (BGU: Ben-Gurion University of the Negev)H-Index: 16
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#1Maria Schwaederle (UCSD: University of California, San Diego)H-Index: 18
#2Gregory A. Daniels (UCSD: University of California, San Diego)H-Index: 24
Last.Razelle Kurzrock (UCSD: University of California, San Diego)H-Index: 99
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#1Maria Schwaederle (UCSD: University of California, San Diego)H-Index: 18
#2Vladimir LazarH-Index: 46
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#1Gerald S. FalchookH-Index: 131
#2Michael Millward (UWA: University of Western Australia)H-Index: 45
Last.Razelle Kurzrock (UCSD: University of California, San Diego)H-Index: 99
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#1Jennifer J. Wheler (University of Texas MD Anderson Cancer Center)H-Index: 32
#2Jiun-Kae Jack Lee (University of Texas MD Anderson Cancer Center)H-Index: 88
Last.Razelle Kurzrock (UCSD: University of California, San Diego)H-Index: 99
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#1Miriam Martini (UNITO: University of Turin)H-Index: 16
#2Maria Chiara De Santis (UNITO: University of Turin)H-Index: 7
Last.Emilio Hirsch (UNITO: University of Turin)H-Index: 67
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#1In Sil Choi (UCSD: University of California, San Diego)H-Index: 1
#2Shumei Kato (UCSD: University of California, San Diego)H-Index: 12
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#1Alex M. Li (UCSD: University of California, San Diego)
#2Amélie Boichard (UCSD: University of California, San Diego)H-Index: 4
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#1Yifeng He (UPenn: University of Pennsylvania)H-Index: 2
#2Zhuowei Gu (SJTU: Shanghai Jiao Tong University)H-Index: 2
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#2Daphne W. Bell (NIH: National Institutes of Health)H-Index: 37
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