By Turna Ray
MOUNTAIN VIEW, Calif. – Following the soft launch of its next-generation sequencing based cancer diagnostic late last year, Foundation Medicine has analyzed 36 samples from patients with solid tumors and found that its test can provide information that doctors can use to make healthcare decisions.
Foundation Medicine has developed an NGS-based cancer diagnostic that analyzes formalin-fixed, paraffin-embedded tissue for variations in more than 200 cancer-related genes. The company is using the test in research efforts with several large pharmaceutical companies and is planning to launch the diagnostic as a lab-developed test later this year.
"We utilize an end-to-end next-gen approach to work with pharmaceutical companies today. We are deeply embedded in many clinical trials as they look for ways to differentiate and stratify patients within [clinical] trials, as they think about products that fail unexpectedly in Phase III trials, and they want to go back and assess that information," Foundation Medicine CEO Michael Pellini said during a talk at the Personalized Medicine World Conference held here this week. "But this information coming out of our work with pharma is also driving our work in our cancer diagnostics business that we kicked off in earnest in the fourth quarter last year."
Foundation Medicine isn't yet marketing its test but began accepting patient samples at the end of 2011. Currently, the test gauges solid tumor samples, but by the end of the year, it will be able to analyze samples from hematological malignancies.
According to Pellini, in analyzing the first 36 patients with solid tumors, the NGS test detected an average of 3.1 alterations per sample. The test failed to analyze two samples, which he said is much better than the failure rate of other diagnostic technologies commonly used at clinical labs today. "The average failure rate in a lab in the US that runs PCR or fluorescent in situ hybridization is 20 percent to 25 percent," Pellini noted.
Pellini highlighted as a positive the fact that the test gauged around three actionable alterations per case. "We're not talking about 10 alterations. We're talking about a very manageable number of clinically relevant alterations," he reflected.
As reported by PGx Reporter sister publication Clinical Sequencing News, the company places "clinically actionable mutations" into three categories. First, an alteration is considered actionable if it can be matched to a specific drug that is on the market, even if it isn't indicated for that particular cancer. Second, mutations tied to therapeutics that are in clinical trials can also provide patients some avenue for acting on the information gleaned from Foundation Medicine's test. A third way that mutations identified by the test can be actionable is if those alterations shed light on active cancer-driving pathways that might help the oncologist treat the patient (CSN 6/8/2011).
In the first 36 patients analyzed by Foundation Medicine's test, it was able to identify three times the number of genomic alterations than the "most broadly available test out on the market," Pellini said, noting that approximately 25 samples had at least one actionable alteration that wouldn't have been found by hot-spot screening.
Around 30 percent of the alterations uniquely identified by the NGS platform were copy number variations, 13 percent were insertions or deletions, 3 percent were gene rearrangements, and nearly 30 percent were substitutions. Pellini couldn't provide more detailed data from this analysis since the company hasn't yet published its findings.
In his presentation, Pellini highlighted one sample from a patient who had a salivary gland tumor. The genomic profile of this type of malignancy is not well studied and the disease has no approved treatments. Patients are usually treated with a broad-spectrum chemotherapeutic.
Testing with the NGS platform, Foundation Medicine researchers identified five actionable alterations that may be responsive to several investigational drugs. While these treatments aren't indicated for this type of tumor, Pellini said he knows that the company running these trials will enroll such patients.
"If you're a patient … and you know you've failed a couple lines of therapy or that there is no good treatment for your disease … do you want to know [these alterations]?" Pellini posited at the meeting. "I think the vast majority, if not all of you in here, would absolutely want to know if it was you, a family member, or one of your patients."
Last year, Foundation Medicine demonstrated the performance of its test by analyzing 75 cancer tissue samples from non-small cell lung cancer, melanoma, and colon cancer. The study, presented during the American Society of Clinical Oncology's annual meeting, showed that the NGS test was in 100 percent concordance with capillary electrophoresis sequencing and mass spectrometry-based tests.
In this analysis, researchers found 214 mutations, including 134 base substitutions, 44 insertions and deletions, 34 copy number alterations, and two structural rearrangements. They concluded that nearly 80 percent of the mutations detected by the NGS test would not have been found using the conventional CE and mass spectrometry-based methods, and over half of the alterations were "clinically actionable."
At PMWC this week, Pellini added to this earlier analysis by reporting more data on NSCLC samples, breast cancer samples, and colorectal cancer samples analyzed by the NGS test. In 95 patients with NSCLC, Foundation Medicine's test found 31 altered genes, 18 of which were clinically actionable. In approximately 30 breast cancer patients, the test similarly identified 11 out of 20 actionable gene alterations, while 19 out of 40 genes found in colorectal cancer patients were deemed actionable.
Pellini said these findings necessitate that healthcare providers and researchers "migrate away from single assays and think about specific alterations that are ultimately the drivers of the pathway of the disease." He noted that there are only a handful of single-mutation tests that oncologists routinely perform on their cancer patients, such as HER2 testing in breast cancer; KRAS testing in colorectal cancer; and EGFR, KRAS, and, more rarely, ALK testing in NSCLC.
Foundation Medicine is also establishing registries and working with oncologists to ensure that the patients tested on the NGS cancer platform are followed over the long term. "We believe that this information will have tremendous value for the payors, for the regulators, for oncologists, pharmaceutical companies, and patients," Pellini said.
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