title: Molecular profiling of advanced solid tumors and patient outcomes with genotype-matched clinical trials: the Princess Margaret IMPACT/COMPACT trial.
abstract: The clinical utility of molecular profiling of tumor tissue to guide treatment of patients with advanced solid tumors is unknown. Our objectives were to evaluate the frequency of genomic alterations, clinical "actionability" of somatic variants, enrollment in mutation-targeted or other clinical trials, and outcome of molecular profiling for advanced solid tumor patients at the Princess Margaret Cancer Centre (PM).
  
  
  
  Patients with advanced solid tumors aged ≥18 years, good performance status, and archival tumor tissue available were prospectively consented. DNA from archival formalin-fixed paraffin-embedded tumor tissue was tested using a MALDI-TOF MS hotspot panel or a targeted next generation sequencing (NGS) panel. Somatic variants were classified according to clinical actionability and an annotated report included in the electronic medical record. Oncologists were provided with summary tables of their patients' molecular profiling results and available mutation-specific clinical trials. Enrolment in genotype-matched versus genotype-unmatched clinical trials following release of profiling results and response by RECIST v1.1 criteria were evaluated.
  
  
  
  From March 2012 to July 2014, 1893 patients were enrolled and 1640 tested. After a median follow-up of 18 months, 245 patients (15 %) who were tested were subsequently treated on 277 therapeutic clinical trials, including 84 patients (5 %) on 89 genotype-matched trials. The overall response rate was higher in patients treated on genotype-matched trials (19 %) compared with genotype-unmatched trials (9 %; p < 0.026). In a multi-variable model, trial matching by genotype (p = 0.021) and female gender (p = 0.034) were the only factors associated with increased likelihood of treatment response.
  
  
  
  Few advanced solid tumor patients enrolled in a prospective institutional molecular profiling trial were treated subsequently on genotype-matched therapeutic trials. In this non-randomized comparison, genotype-enrichment of early phase clinical trials was associated with an increased objective tumor response rate.
  
  
  
  NCT01505400 (date of registration 4 January 2012).
authors: Laboratory Medicine Program, University Health Network, Toronto, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.|Cancer Genomics Program, Princess Margaret Cancer Centre, Toronto, Canada.
authors: Tracy L
authors: TL
authors: Stockley
authors: Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, M5G 2M9, Canada.|Department of Medicine, University of Toronto, Toronto, Canada.
authors: Amit M
authors: AM
authors: Oza
authors: Laboratory Medicine Program, University Health Network, Toronto, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
authors: Hal K
authors: HK
authors: Berman
authors: Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, M5G 2M9, Canada.|Department of Medicine, University of Toronto, Toronto, Canada.
authors: Natasha B
authors: NB
authors: Leighl
authors: Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, M5G 2M9, Canada.|Department of Medicine, University of Toronto, Toronto, Canada.
authors: Jennifer J
authors: JJ
authors: Knox
authors: Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, M5G 2M9, Canada.|Department of Medicine, University of Toronto, Toronto, Canada.
authors: Frances A
authors: FA
authors: Shepherd
authors: Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, M5G 2M9, Canada.|Department of Medicine, University of Toronto, Toronto, Canada.
authors: Eric X
authors: EX
authors: Chen
authors: Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, M5G 2M9, Canada.|Department of Medicine, University of Toronto, Toronto, Canada.
authors: Monika K
authors: MK
authors: Krzyzanowska
authors: Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, M5G 2M9, Canada.|Department of Medicine, University of Toronto, Toronto, Canada.
authors: Neesha
authors: N
authors: Dhani
authors: Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, M5G 2M9, Canada.|Department of Medicine, University of Toronto, Toronto, Canada.
authors: Anthony M
authors: AM
authors: Joshua
authors: Laboratory Medicine Program, University Health Network, Toronto, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, Canada.
authors: Ming-Sound
authors: MS
authors: Tsao
authors: Laboratory Medicine Program, University Health Network, Toronto, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
authors: Stefano
authors: S
authors: Serra
authors: Laboratory Medicine Program, University Health Network, Toronto, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
authors: Blaise
authors: B
authors: Clarke
authors: Laboratory Medicine Program, University Health Network, Toronto, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, Canada.
authors: Michael H
authors: MH
authors: Roehrl
authors: Laboratory Medicine Program, University Health Network, Toronto, Canada.
authors: Tong
authors: T
authors: Zhang
authors: Laboratory Medicine Program, University Health Network, Toronto, Canada.
authors: Mahadeo A
authors: MA
authors: Sukhai
authors: Department of Oncology, Grand River Regional Cancer Centre, Kitchener-Waterloo, Canada.|Department of Oncology, McMaster University, Faculty of Health Sciences, Hamilton, Canada.
authors: Nadia
authors: N
authors: Califaretti
authors: Department of Medicine, Markham Stouffville Hospital, Markham, Canada.
authors: Mateya
authors: M
authors: Trinkaus
authors: Laboratory Medicine Program, University Health Network, Toronto, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
authors: Patricia
authors: P
authors: Shaw
authors: Laboratory Medicine Program, University Health Network, Toronto, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
authors: Theodorus
authors: T
authors: van der Kwast
authors: Department of Biostatistics, Princess Margaret Cancer Centre, Toronto, Canada.
authors: Lisa
authors: L
authors: Wang
authors: Cancer Genomics Program, Princess Margaret Cancer Centre, Toronto, Canada.|Princess Margaret Research Institute, Princess Margaret Cancer Centre, Toronto, Canada.
authors: Carl
authors: C
authors: Virtanen
authors: Cancer Genomics Program, Princess Margaret Cancer Centre, Toronto, Canada.|Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, M5G 2M9, Canada.|Department of Medicine, University of Toronto, Toronto, Canada.
authors: Raymond H
authors: RH
authors: Kim
authors: Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, M5G 2M9, Canada.|Department of Medicine, University of Toronto, Toronto, Canada.
authors: Albiruni R A
authors: AR
authors: Razak
authors: Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, M5G 2M9, Canada.|Department of Medicine, University of Toronto, Toronto, Canada.
authors: Aaron R
authors: AR
authors: Hansen
authors: Cancer Genomics Program, Princess Margaret Cancer Centre, Toronto, Canada.
authors: Celeste
authors: C
authors: Yu
authors: Cancer Genomics Program, Princess Margaret Cancer Centre, Toronto, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, Canada.|Princess Margaret Research Institute, Princess Margaret Cancer Centre, Toronto, Canada.
authors: Trevor J
authors: TJ
authors: Pugh
authors: Laboratory Medicine Program, University Health Network, Toronto, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.|Cancer Genomics Program, Princess Margaret Cancer Centre, Toronto, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, Canada.
authors: Suzanne
authors: S
authors: Kamel-Reid
authors: Cancer Genomics Program, Princess Margaret Cancer Centre, Toronto, Canada.|Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, M5G 2M9, Canada.|Department of Medicine, University of Toronto, Toronto, Canada.
authors: Lillian L
authors: LL
authors: Siu
authors: Cancer Genomics Program, Princess Margaret Cancer Centre, Toronto, Canada. philippe.bedard@uhn.ca.|Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, M5G 2M9, Canada. philippe.bedard@uhn.ca.|Department of Medicine, University of Toronto, Toronto, Canada. philippe.bedard@uhn.ca.
authors: Philippe L
authors: PL
authors: Bedard
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002170:Canada; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods*; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D066066:Response Evaluation Criteria in Solid Tumors; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm
keywords: Clinical trials; DNA sequencing; Molecular profiling; Precision medicine; Solid tumors