By Turna Ray

Fresh on the heels of launching Oncotype DX for colorectal cancer recurrence in stage II patients last week, Genomic Health is already working on expanding the indication of the test into later stages of the disease as well as into renal cancer, ductal carcinoma in situ, and prostate cancer.

Oncotype DX for colorectal cancer analyzes the expression of 12 genes to yield a recurrence score that indicates the likelihood of stage II disease recurrence following surgery. Genomic Health developed the test with collaborators at the National Surgical Adjuvant Breast and Bowel Project, the Cleveland Clinic, and the QUASAR study group.

In order to develop the RT-PCR based test, researchers looked at more than 700 genes in more than 1,800 colon cancer patients. The final set of 12 genes used to yield the recurrence score for the test was independently validated in 1,436 stage II colon cancer patients in the QUASAR trial.

In the trial, the test met its primary endpoint in determining the likelihood of post-operative disease recurrence in patients with stage II colon cancer, but the study did not meet its secondary endpoint when using the test to predict which patients are likely to benefit with post-operative 5-fluorouracil/leucovorin treatment [see PGx Reporter 04-15-2009].

Despite not being able to offer a separate treatment score for predicting chemotherapy benefit with the initial launch of the test, Genomic Health is not giving up on the predictive indication. Depending on the results of additional studies, the company hopes to be able to offer a separate predictive treatment score for Oncotype DX colorectal cancer by 2013.

"Just as we did with Oncotype DX breast cancer — we started out and reported recurrence risk alone and then did additional tests over time that enhanced the value of the test — we're doing the exact same thing in colon cancer and doing additional studies to look at chemotherapy benefit … particularly with oxaliplatin," Steven Shak, Genomic Health's chief medical officer, told Pharmacogenomics Reporter this week.

In addition to the predictive claim, the company presented data at a major oncology conference last week that suggests the test might be clinically useful in detecting recurrence in stage III colorectal cancer patients.

Separately, the company is also planning to report results from a collaborative study with Pfizer focusing on identifying prognostic markers for renal cancer sometime this year, Shak said.

CRC Test Launch and Adoption

Following the release of data from the QUASAR trial last year, analysis by Thomas Weisel Partners showed that investors were disappointed that Genomic Health's colorectal cancer test was not predictive for chemotherapy benefit. However, a survey of oncologists and pathologists, also conducted around the same time by Thomas Wiesel, suggested healthcare providers were interested in using the test in their practices without the predictive claim [see PGx Reporter 07-15-2009].

Shak doesn't believe that not having the predictive claim for the colon cancer test will negatively affect adoption. In fact, he suggested that even without a separate treatment score to predict response to chemotherapy, doctors can use the prognostic recurrence score alongside standard clinical measures to discern which patients should receive chemotherapy.

"When you actually look at the recurrence risk, it's actually the recurrence risk that doctors use to provide an estimate of the magnitude of the benefit of chemotherapy," Shak said. "When we did the QUASAR study, we looked at the relative risk reduction as a function of the recurrence score. As the recurrence score increases, we estimate that the actual magnitude of the chemotherapy benefit is going to be greater in those patients.