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St. Gallen's Recommendations May Impact Adoption of Leading Breast Cancer Genetic Tests

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By Turna Ray

Updated recommendations by the St. Gallen's International Expert Consensus panel on the primary treatment of early breast cancer advise the use of multi-gene assays to determine which patients should receive adjuvant chemotherapy.

The recommendations by the expert group, which met in Switzerland in March and involves healthcare leaders from around the world, including the US, could impact the adoption of and reimbursement for breast cancer genetic tests, such as Agendia's MammaPrint and Genomic Health's Oncotype DX.

The 11th St. Gallen meeting "maintained an emphasis on targeting adjuvant systemic therapies according to subgroups defined by predictive markers," members of the consensus group wrote in a paper published June 17 in the Annals of Oncology. "Proliferation markers, including those identified in multi-gene array analyses, were recognized as important" in recognizing the role of risk factors.

This is the first time St. Gallen's experts have recommended the use of predictive multi-gene tests in the treatment of early breast cancer. Although the meeting took place in Europe, the recommendations could have an international impact since the St. Gallen expert panel comprises opinion leaders from across Europe (53 percent), the United States (33 percent), and other countries (14 percent).

"St. Gallen's guideline inclusion is a key step in further establishing MammaPrint as a standard of care," Bernhard Sixt, Agendia's CEO, said in a statement.

Separately, the investment group Thomas Weisel Partners issued a note that "these new guidelines highlight the continued clinical acceptance of Oncotype [DX] in the breast cancer setting, fortify its competitive position, and could help create a larger push for uptake in Europe."

According to Thomas Weisel's analysis, since the St. Gallen's meeting was "more European-focused," the guidelines could bolster Oncotype DX sales in international markets, which Genomic Health has said it is focused on growing. Currently, international revenue makes up less than 10 percent of Genomic Health's revenues for Oncotype DX.

While the St. Gallen's group "agreed that validated multi-gene tests, if readily available, could assist in deciding whether to add chemotherapy in cases where its use was uncertain," experts found that intermediate scores from such multi-gene tests provide "little guidance in reaching a decision to use chemotherapy."

This is perhaps a finer point that could work in favor of Agendia as it tries to bolster the adoption and coverage of MammaPrint, a test that is in competition with Genomic Health's Oncotype DX.

MammaPrint provides a binary result, placing patients either in the "high risk" category who should receive hormone therapy and chemotherapy, or in the "low risk" category who should receive just hormone therapy.

Oncotype DX's Recurrence Score places patients in three categories, high, intermediate, and low risk. Patients with an intermediate risk, receiving scores of 11 to 25, have a breast cancer recurrence rate of between 7 percent and 16 percent. The effects of adjuvant chemotherapy plus hormonal therapy in this group of women, representing approximately 44 percent of node-negative, hormone-positive breast cancer patients, are unknown.

"Patients with an intermediate score don't end up with data that allows the medical oncologist to make any more informed decision than they had before doing the test," Richard Bender, Agendia's chief medical officer, told Pharmacogenomics Reporter this week. "The St. Gallen's group is really standing behind tests that have a binary result, tests that don't provide an intermediate score."

Genomic Health did not respond to questions about the St. Gallen's guidelines prior to deadline. In a statement, however, the company touted the recommendations as an endorsement of the role multi-gene assays play in guiding breast cancer treatment.

The guidelines "represent a significant advancement for the role of validated molecular diagnostics in breast cancer treatment planning and selection in Europe," Genomic Health said in a statement. "Clinical research in the United States and other countries shows that information obtained from multigene assays, including Oncotype DX, leads to a change in treatment decisions in approximately 30 percent of cases."

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To determine whether patients with an intermediate risk score will benefit by adding adjuvant chemotherapy to adjuvant hormonal therapy, Oncotype DX is being used in the Trial Assigning IndividuaLized Options for Treatment (Rx), also known as TAILORx.

The trial, sponsored by the National Cancer Institute, will enroll more than 10,000 women who have been diagnosed with estrogen-receptor-positive and/or progesterone-receptor-positive, Her2/neu-negative breast cancer that has not yet spread to the lymph nodes. The clinical trial, taking place at 900 sites in the US and elsewhere, is one of the largest randomized trials being performed in women with localized breast cancer.

Meanwhile, at the American Society of Clinical Oncology's annual meeting last month, Agendia also presented several studies on the clinical validity, clinical utility, and cost-effectiveness of MammaPrint, which was the first IVDMIA to garner clearance from the FDA in 2007 [see PGx Reporter 06-03-2009].

Even though MammaPrint has FDA clearance, when compared to the market success of Genomic Health's Oncotype DX test, Agendia's test has not been as widely adopted by oncologists in the US and many insurers have yet to reimburse for the test.

According to Genomic Health, physicians have used Oncotype DX for breast cancer treatment planning in more than 100,000 patients in over 40 countries worldwide. The company has secured coverage for breast cancer patients with lymph node micro-metastases for more than 100 million US insured lives, which comprises 40 percent of the patient population.

According to Bender, since the St. Gallen's group issued its recommendations, Agendia has seen an uptick in the number of payors in the US covering the test. Agendia is speaking to several major payors currently and expects to have more than 100 million lives covered for MammaPrint in the US within the next six to 12 months.

"Payors were looking for this kind of endorsement from a major sanctioning body [that includes] key US opinion leaders. Payors were looking for an indication that MammaPrint is both prognostic and predictive," Bender said. "Payors are now much keener to engage us, including CMS."

Given the presentation of predictive data on MammaPrint at ASCO's annual meeting, Agendia is also hoping to be included in updated guidelines from the National Comprehensive Cancer Network. "They are reviewing our data, and we're hoping to hear from them in the coming weeks," Bender said.

Oncotype DX is currently the only multi-gene expression assay recommended in both the ASCO and the NCCN guidelines.

Although recommendations from ASCO and NCCN are most commonly used by oncologists in the US, studies have shown that treatment guidelines from the St. Gallen's group have had a major impact on clinical practice. A study published in the Annals of Oncology in 2007 by Italian researchers found that based on St. Gallen recommendations, in breast cancer patients the use of aromatase inhibitors doubled, administration of anthracycline-based chemotherapy increased, and the use of taxanes in combination with hormones dropped.

Agendia had previously said it intended to seek an updated label from the FDA for MammaPrint to include the predictive claims for the assay. This would put MammaPrint more directly in competition with OncotypeDx as both a predictive and prognostic multi-gene breast cancer assay. Submission plans for this labeling update are now on hold as the company focuses on growing its presence in the US.

"We haven't made a decision as a company as to whether we will pursue the predictive claim" for MammaPrint with the FDA, Bender said. "Right now, it's just exigencies. We're in the process of expanding the company and resources are necessary for that. This is a function of manpower and time."

Agendia, which is headquartered in Amsterdam, opened on June 15 a new CLIA-certified laboratory in Huntington Beach, Calif., where it will process all samples from US physicians. A US-based lab will likely help Agendia compete with Genomic Health in terms of providing faster turnaround of test results.

For now, the company plans to update only the age designation for MammaPrint in labeling, changing the indication from up to 61 years of age to up to and including 83 years, Bender said. Agendia expects to hear a favorable decision from the FDA on July 20 in this regard.

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