Related Experiment Video
Updated: Mar 13, 2026
Author Spotlight: Integrating High-Resolution Intravital Imaging and MRI to Enhance Stereotactic Body Radiation Therapy Planning
Published on: April 12, 2024
Molecular profiling of advanced solid tumors and patient outcomes with genotype-matched clinical trials: the Princess
Tracy L Stockley1,2,3, Amit M Oza4,5, Hal K Berman1,2
1Laboratory Medicine Program, University Health Network, Toronto, Canada.
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 < 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.
Conclusions:
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.
Trial Registration:
NCT01505400 (date of registration 4 January 2012).
Insights
Molecular profiling of advanced solid tumors identified genomic alterations. Patients treated on genotype-matched clinical trials showed a higher response rate, suggesting improved outcomes with targeted therapies.
Area of Science:
- Oncology
- Genomics
- Clinical Trials
Background:
- The clinical utility of molecular profiling for advanced solid tumors remains unclear.
- This study evaluated genomic alterations, clinical actionability, and trial enrollment in advanced solid tumor patients.
Purpose of the Study:
- To assess the frequency of genomic alterations in advanced solid tumors.
- To determine the clinical actionability of somatic variants.
- To evaluate clinical trial enrollment and outcomes following molecular profiling.
Main Methods:
- Prospective enrollment of advanced solid tumor patients with available tumor tissue.
- DNA analysis using hotspot panels or next-generation sequencing (NGS).
- Classification of variants by actionability and tracking of clinical trial enrollment.
Main Results:
- 1640 patients were tested, revealing genomic alterations.
- 15% of tested patients enrolled in clinical trials, with 5% in genotype-matched trials.
- Higher response rates (19%) were observed in genotype-matched trials compared to unmatched (9%).
Conclusions:
- Few patients were treated on genotype-matched trials, despite potential benefits.
- Genotype-enrichment in early-phase trials correlated with increased objective tumor response rates.
- Molecular profiling may guide treatment decisions and improve outcomes in advanced solid tumors.
More Related Videos
12:09A Novel High-resolution In vivo Imaging Technique to Study the Dynamic Response of Intracranial Structures to Tumor Growth and Therapeutics
Published on: June 16, 2013
09:00Spatial Measurements of Perfusion, Interstitial Fluid Pressure and Liposomes Accumulation in Solid Tumors
Published on: August 18, 2016