Summary

An overview of how FoundationOne can assist clinicians in choosing suitable therapies or clinical trials for their patients, potentially improving clinical outcomes.
Treatment Options

FoundationOne can help to guide clinicians in determining the most effective therapy for their patients

FoundationOne has been used to profile over 150,000 patients,1 with many patients being shown to have had at least 1 clinically relevant alteration (~90% of patients).2–4 Numerous studies have shown that the use of biomarker-directed therapies, following the identification of such alterations, is associated with significantly improved clinical outcomes in patients compared with a non-targeted approach.5–7

There is increasing recognition that broader profiling is an effective strategy to help to identify both common and rare mutations in a patient’s cancer, so that targeted, biomarker-directed therapy options may be identified.8–10 Broad molecular profiling, such as with FoundationOne, can identify alterations in all driver genes listed, and recommended for testing, by the National Comprehensive Cancer Network (NCCN).8 For example, 71% of genomic alterations identified in non-small cell lung cancer (NSCLC) samples profiled using FoundationOne were found to have an alteration in at least 1 of these drivers.11

These alterations may otherwise go undetected and, as a result, broad molecular profiling is now strongly recommended by NCCN guidelines in the diagnosis and treatment of NSCLC.8

“The NCCN Panel strongly advises broader molecular profiling (also known as precision medicine) to identify rare driver mutations to ensure patients receive the most appropriate treatment”

NCCN Guidelines for NSCLC Version 9, 2017
Improved outcomes

Biomarker-directed treatment strategies have been associated with improved clinical outcomes

Across multiple meta-analyses, biomarker-directed therapies have demonstrated significantly improved response rates (RR), progression-free survival (PFS) and overall survival (OS) when compared to a non-biomarker-directed approach.5–7 Use of a personalised, biomarker-directed anticancer treatment strategy has also been identified as an independent predictor of improved outcomes and fewer toxic deaths compared with a routine, non-personalised approach.5
Relevant alterations

FoundationOne can detect clinically relevant alterations in the majority of patients, in a broad range of cancers

Genomic profiling with FoundationOne can open up treatment possibilities for patients through the identification of clinically relevant alterations within their tumour. Utilising hybrid capture-based next-generation (NGS) technology, FoundationOne profiling analyses entire exomes (the coding regions of the DNA) of 315 cancer-related genes, meaning that even rare alterations may be identified.9,12

FoundationOne genomic profiling was proven to facilitate a more comprehensive and efficient strategy in a study of 31 lung adenocarcinoma patients, when compared to non-NGS testing methods. The study found that actionable genomic alterations could be detected in 65% of patients who were previously deemed to be without targetable genomic alterations by earlier non-NGS testing.10

This improved detection was also confirmed in a study of 5,605 advanced and metastatic breast cancers that were analysed using FoundationOne to assess the frequency of alterations in the breast cancer-related gene ERBB2. It was found that 12.5% of patients (698/5,605) featured ERBB2 alterations, with 1.8% of patients harbouring a type of alteration that would be undetectable by standard of care methods.13

The majority of identified alterations with FoundationOne could be targeted with either approved or investigational therapies
In a retrospective analysis of 439 patients who underwent FoundationOne tumour profiling, at least 1 potentially actionable alteration was identified per patient (90%; 393/439). Of all patients profiled, an average of 3 alterations (range, 0–16) were identified in each patient, with an average of 2 (range, 0–8) of these alterations potentially able to be targeted by either an approved or investigational therapy. Of these patients, 59% (257/439) had metastatic disease and in 70% (307/439) of cases, the alteration could be targeted with an approved therapy indicated for that tumour type (20%; 89/439) and/or for another tumour type (67%; 296/439). For all patients with ≥1 alteration, there was an investigational therapy in clinical trials available (90%; 393/439).4
FoundationOne can identify potentially clinically relevant genomic alterations to address the limited options available for patients with cancers of unknown primary origin

Currently, there are very limited therapeutic options specifically approved for the treatment of what are known as cancers of unknown primary origin (CUP) and, in general, patients presenting for chemotherapy as treatment for CUP respond poorly. In order to identify potential clinically relevant alterations, 200 patients with CUP were profiled using FoundationOne. 85% of patients (169/200) had at least 1 clinically relevant alteration that could facilitate therapeutic decisions. Additionally, this study identified 26 genomic alterations associated with targeted therapies approved for use in patients with a known primary tumour type.14 
Support decision-making

Profiling with FoundationOne can impact clinical decision making

Genomic profiling with FoundationOne has been shown by several studies to facilitate clinical decisions and specific patient disease management.15–17

BREAST CANCER
A prospective trial in advanced breast cancer demonstrated that 41% of patients (34/83) were recommended a change in therapy based on their genomic profiling results.15
LUNG CANCER
A retrospective study of 101 patients with advanced lung carcinoma demonstrated that over 44% (34/77) of patients profiled using FoundationOne received a change in therapy following genomic profiling.16
RARE CANCER

In a prospective clinical study of 100 patients with diverse, rare or poor prognosis, 92 underwent genomic profiling using FoundationOne.

95% of these patients (87/92) were recommended a clinical action or investigational trial.17

Clinical evidence

Clinical trial evidence supporting genomic profiling using FoundationOne

Work is ongoing to clinically evaluate the impact that genomic profiling techniques can have on patients’ lives. Genomic profiling, such as that offered by FoundationOne, has been proven to improve outcomes through the actioning of identified clinically relevant alterations compared with non-personalised approaches and non-targeted therapies.5,15–17

FoundationOne’s personalised approach offers patients more treatment options, potentially improving clinical outcomes vs. a non-personalised approach
A study using FoundationOne profiling in 339 patients across a variety of cancers found that 93.5% had at least 1 potentially actionable alteration (317/339). Through the calculation of matching scores based on the number of drug matches and genomic alterations per patient, it was determined a higher matching score was associated with a greater frequency of stable disease (22% vs. 9%; p=0.024), a longer time to treatment failure (HR=0.52; p=0.0003) and survival (HR=0.65, p=0.05), compared to a lower matching score. Further study of the clinical implications of these data is needed.18
Targeted therapies identified with FoundationOne can result in improved progression-free survival vs. non-targeted therapies

In a retrospective study of 347 patients presenting with advanced solid tumours for whom tumour profiling had been performed using FoundationOne, patients who subsequently received targeted therapy had significantly higher RR and PFS compared with those not receiving targeted therapy.19

These findings are corroborated by other studies that have compared the impact of targeted therapies identified with FoundationOne, across a broad range of cancer types:
Advanced lung carcinoma
A study in advanced lung carcinoma found that, among the 44.2% (34/77) of patients who had a change in treatment strategy based on FoundationOne profiling results, the overall RR to their new therapeutics was over 51.5% (1 patient was excluded from overall RR calculation).16
Metastatic breast cancer
FoundationOne profiling of 44 metastatic breast cancer patients revealed that 23 patients had a clinically relevant alteration and, subsequently, 35% of these patients derived a clinical benefit from initiated targeted therapy.20
Advanced gastrointestinal cancer
Targeted therapy was used in 13.7% (13/95) of advanced gastrointestinal cancer patients profiled using FoundationOne, resulting in over 50% (7/13) of these patients deriving a clinical benefit.21
Gynaecological cancers
FoundationOne profiling results of 64 patients presenting with rare or refractory gynaecological cancers showed that, of these patients, 25 went on to receive a targeted therapy based on their FoundationOne results. 64% (16/25) of these patients demonstrated a response, stable disease or other clinical benefit.3

These studies show the potential of broad genomic profiling across solid cancer types, but much work is still ongoing to further validate these data. New studies and further examination of existing data will allow us to continually build upon the clinical benefits of selecting therapies based on genomic profiling results.
References
  1. Genomeweb. Foundation Medicine Q3 revenues up 45 percent. Available at: https://www.genomeweb.com/molecular-diagnostics/foundation-medicine-q3-revenues-45-percent [accessed November 2017].
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  3. Rodriguez-Rodriguez L et al. Gynecol Oncol 2016; 141:2–9.
  4. Schwaederle M et al. Mol Cancer Ther 2015; 14:1488–1494.
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  6. Schwaederle M et al. JAMA Oncol 2016; 2:1452–1459.
  7. Jardim DL et al. J Natl Cancer Inst 2015; 107:e253.
  8. National Comprehensive Cancer Network (NCCN) NSCLC guidelines, Version 9, 2017.
  9. Frampton, GM et al. Nat Biotechnol 2013; 31:1023–1031
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  11. Suh JH et al. Oncologist 2016; 21:684–691.
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  14. Ross JS et al. JAMA Oncol 2015; 1:40–49.
  15. Reinbolt RE et al. J Clin Oncol 2016; 34 (and supplementary material).
  16. Rozenblum AB et al. J Thorac Oncol 2017; 2:258–268 (and supplementary material).
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  18. Wheler JJ et al. Cancer Res 2016; 76:3690–3701.
  19. Schwaederle M et al. Mol Cancer Ther 2016; 15:743–752.
  20. Yuan Y et al. Oncotarget 2017; 8:26414–26423.
  21. Dhir M et al. Cancer Med 2017; 1:195–206.