Molecular profiling of advanced solid tumors and patient outcomes with genotype-matched clinical trials: the Princess Margaret IMPACT/COMPACT trial

Autor: Nadia Califaretti, Lillian L. Siu, Neesha C. Dhani, Mateya Trinkaus, Trevor J. Pugh, Carl Virtanen, Tong Zhang, Theodorus van der Kwast, Blaise A. Clarke, Eric X. Chen, Albiruni Ryan Abdul Razak, Natasha B. Leighl, Mahadeo A. Sukhai, Hal K. Berman, Michael H.A. Roehrl, Anthony M. Joshua, Patricia Shaw, Amit M. Oza, Ming-Sound Tsao, Monika K. Krzyzanowska, Suzanne Kamel-Reid, Aaron R. Hansen, Frances A. Shepherd, Lisa Wang, Raymond H. Kim, Jennifer J. Knox, Stefano Serra, Tracy Stockley, Philippe L. Bedard, Celeste Yu
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Oncology
Male
lcsh:Medicine
Bioinformatics
Molecular profiling
0302 clinical medicine
Clinical trials
Gene Frequency
Neoplasms
Genotype
Solid tumors
Genetics(clinical)
DNA sequencing
Molecular Targeted Therapy
Young adult
Genetics (clinical)
Aged
80 and over
Precision medicine
High-Throughput Nucleotide Sequencing
DNA
Neoplasm
Middle Aged
Immunohistochemistry
Response Evaluation Criteria in Solid Tumors
030220 oncology & carcinogenesis
Molecular Medicine
Female
Early phase
Adult
medicine.medical_specialty
Canada
lcsh:QH426-470
Adolescent
03 medical and health sciences
Young Adult
Internal medicine
medicine
Genetics
Biomarkers
Tumor
Humans
Genetic Predisposition to Disease
Allele frequency
Molecular Biology
Aged
Performance status
business.industry
Research
lcsh:R
Clinical trial
lcsh:Genetics
030104 developmental biology
Mutation
business
Zdroj: Genome Medicine
Genome Medicine, Vol 8, Iss 1, Pp 1-12 (2016)
ISSN: 1756-994X
Popis: Background 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). Methods 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. Results 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
Databáze: OpenAIRE
Externí odkaz: