Von Hoff DD, Stephenson JJ Jr, Rosen P, et al. Pilot study using molecular profiling of patients’ tumors to find potential targets and select treatments for their refractory cancers. J Clin Oncol. 2010; 28(33):4877-83.

Pilot study shows applicability of Caris Molecular Intelligence to improve patient outcomes in clinical practice.

A highly regarded pilot study from 20101 was the first to show the applicability of multiplatform molecular tumour profiling in clinical practice, enrolling patients from nine centres across the United States. The study aimed to investigate whether the current technologies used in molecular profiling were able to identify treatments that were better than a clinician’s planned treatment regime.

There were 106 patients enrolled in the study and they all had advanced solid tumours that were refractory to at least two lines of standard therapy. Of these 106 participants, 86 underwent tumour multiplatform molecular profiling. Known as Target Now, the molecular profiling included immunohistochemistry (IHC) testing, fluorescent in situ hybridisation (FISH) testing and DNA microarray testing. It is important to note that this study predated the use of next generation sequencing (NGS), which is included in Target Now’s successor, Caris Molecular Intelligence molecular profiling.

The remaining 20 patients did not undergo molecular profiling for various reasons, the most common being that their condition worsened. The same reasons meant that 18 patients were not treated after molecular profiling. In total, 68 patients were treated after molecular profiling, of whom 66 were treated in line with the results of profiling and two were not. Of note, 27% of the patients had breast cancer, 17% had colorectal cancer, 8% had ovarian cancer, and 48% were in the miscellaneous category with many rare types of cancer.

Eighteen patients out of the 66 who were treated according to their profiling results (27%) experienced a progression free survival (PFS) ratio ≥ 1.3. This ratio was determined by comparing the PFS using the treatment recommended by molecular profiling with the PFS for the most recent line of therapy for which the patient had progressed. In addition, 21% of patients saw no progression after 4 months of follow up. Promisingly, some shrinkage of tumours were seen in more than 47% of the patients.

The researchers also found that there was no relationship between the therapy that the physician would have chosen to treat the patient had molecular profiling not been performed, and what was recommended by profiling. Importantly there were no matches at all for any of the patients who experienced a PFS ratio ≥ 1.3. This finding outlines the difficulty in choosing therapies for patients with refractory disease.

An important consideration is that this study was performed in 2010. Since then, Caris Molecular Intelligence profiling has grown to include 592 biomarkers through NGS, as well as more extensive IHC panels and RNA testing. This pilot study showed that it was possible to perform molecular profiling on a patient’s tumour sample and recommend treatments from this profile. It showed that these treatments could be implemented in various clinical settings to benefit patients. Since this pilot study, this finding is something that has been echoed in the literature.

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Summary

  • Dr Dan von Hoff was the first to develop multiplatform molecular profiling and create a workflow in the laboratory that was able to support patients from different locations in the US. He started a ground breaking clinical study of the benefits from molecular profiling in 2003.
  • This pilot study published in 2010 was the first to show the clinical utility of multiplatform molecular profiling in clinical practice across multiple centres in the United States.
  • 27% of patients treated in line with the results of molecular profiling experienced a PFS ratio ≥ 1.3.
  • 21% of patients also saw no progression after 4 months and 47% of patients saw some shrinkage in the size of their tumours.

Reference

  1. Von Hoff DD, Stephenson JJ Jr, Rosen P, et al. Pilot study using molecular profiling of patients’ tumors to find potential targets and select treatments for their refractory cancers. J Clin Oncol. 2010; 28(33):4877-83. [PDF]
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