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Validation Study for NanoString Prosigna Recurrence Test Published in JCO

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Originally published July 9.

Researchers from Royal Marsden Hospital, NanoString, and elsewhere published data in the Journal of Clinical Oncology from a study in which they showed that the PAM50 risk of recurrence score provides more prognostic information than Genomic Health's Oncotype DX in gauging the risk of recurrence for women with ER-positive, early stage breast cancer.

This is the first published validation study involving NanoString's Prosigna Breast Cancer Prognostic Gene Signature Assay, which uses the PAM50 gene signature.

Researchers led by Mitch Dowsett from Royal Marsden Hospital analyzed samples from more than 1,000 patients previously enrolled in the Arimidex, Tamoxifen, Alone or in Combination, or ATAC, trial. The study authors then compared the recurrence estimates by NanoString's test against the recurrence estimates on the same patients by Oncotype DX and IHC4.

The study revealed that the PAM50 signature was able to classify more patients as being at high risk of recurrence compared to Oncotype DX, and fewer patients as intermediate risk. "Populations of similar size were estimated to be low risk with [Prosigna] or [Oncotype DX], although these were not identical groups of patients," Dowsett and colleagues wrote. "[Prosigna] segregated more patients to higher risk and fewer to intermediate risk than [Oncotype DX]."

According to Dowsett and colleagues, the Prosigna recurrence estimates were likely more accurate than Oncotype DX in placing more patients in the high-risk category since the hazard ratios between the low- and high-risk groups "marginally improved" using PAM50 compared to Oncotype DX. "Thus, the tests would have similar performance for patient decision making," the authors wrote. "Limited data indicated that the high-risk group as identified by [Oncotype DX] gained benefit from chemotherapy, with the intermediate group apparently gaining little."

The data from this published study was first presented at the San Antonio Breast Cancer Symposium in 2011, at which time PGx Reporter covered the study in detail (PGx Reporter 12/14/2011).

PAM50 is an RT-PCR test that measures 50 classifier genes and five control genes and categorizes patients into five intrinsic breast cancer subtypes that confer prognostic information: luminal A, luminal B, HER2-enriched, basal-like, and normal-like. The company runs Prosigna on its nCounter Analysis System and late last year filed a 510(k) application with the US Food and Drug Administration.

Genomic Health's Oncotype DX is a 21-gene RT-PCR assay that has been on the market as a lab-developed test since 2004. The gene-expression test provides a score between one and 100 indicating the recurrence risk – high, intermediate, or low – over 10 years for women with HER2-negative, ER-positive, early-stage breast cancer that hasn't spread to the lymph nodes. The company also markets the test for women with hormone receptor-positive, lymph node-positive breast cancer patients.

Based on the Oncotype DX recurrence score, if patients are deemed to be at low risk, studies have shown that they can forgo chemotherapy and can do well with only hormone therapy. However, it is unclear if those at intermediate risk would benefit from chemotherapy. Several large studies, TAILORx and RxPONDER, are investigating this question.

In the JCO paper researchers also compared PAM50 against IHC4, which is an immunohistochemistry test that derives a recurrence score based on quantifying ER, progesterone receptor, Ki67, and HER2. Dowsett and colleagues reported that IHC4 added as much prognostic information as Prosigna in the overall study population, but PAM50 added "significantly more" information than IHC4 in HER2-negative, node-negative patients.

NanoString will likely use this validation study to bolster its marketing activities for Prosigna. The PAM50 test has CE marking in the EU and NanoString began offering the test in Europe and Israel earlier this year. However, the company is in a quiet period and could not answer questions about its test commercialization plans.

NanoString earlier this year announced its intention to go public. In June, the company priced its initial public offering at $10 per share.

Additionally, according to documents filed with the US Securities and Exchange Commission, the FDA has asked NanoString to submit additional data as part of its 510(k) filing for Prosigna. The company still expects to launch the test in the US in the first quarter of 2014.

NanoString launched the second validation study for the PAM50 test last year. In that retrospective trial, researchers will analyze 1,000 samples from patients enrolled in the Austrian Breast & Colorectal Cancer Study Group 8 trial. Launched in 1996, ABCSG8 compared the efficacy and safety of tamoxifen as a single agent versus tamoxifen followed by anastrozole in post-menopausal, hormone receptor-positive early-stage breast cancer patients (PGx Reporter 5/16/2012).

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