In a plenary talk about cancer genomics at this week's 100th annual meeting of the American Association for Cancer Research (AACR; Philadelphia) in Denver, Eric Lander, founding director of Broad Institute, said he hopes to see complete cancer genome analyses become a routine part of research within five years and a standard of care for patients within 10 years.
Lander specified that his goal was a "hope" rather than a prediction – which some might consider too lofty. But a sampling of data from the AACR conference reveals plenty of progress down the personalized medicine path.
One presentation that garnered attention was that of Translational Genomics Research Institute (Phoenix) scientist Daniel Von Hoff, who used molecular profiling to drive treatment decisions for 66 relapsed and refractory cancer patients, resulting in improved progression-free survival for 18 patients.
Von Hoff collected tumor samples from patients with various kinds of metastatic disease who had failed an average of about four prior therapies, although some patients had failed as many as 13 treatments. The samples were analyzed using Target Now, an oncology testing service marketed by Caris Diagnostics (Irving, Texas). Through DNA microarray and immunohistochemical analyses, the service was able to identify biomarkers in all patients pointing to the potential utility of various approved drugs.
Of the 66 patients treated according to the biomarker analysis, 18 patients (27%) had a clinically significant improvement in progression free survival. Additionally 47 patients (71%) experienced tumor shrinkage, and six patients (9%) experienced dramatic tumor shrinkage.
Other presentations at the conference focused on new ways to identify cancer biomarkers and diagnose cancer.
Life Technologies Corp. subsidiary Applied Biosystems (Carlsbad, California) touted its SOLiD System as a tool for identifying methylation patterns across the genome, which may serve as new cancer biomarkers.
Meanwhile researchers from the University of Southern California and the California Institute of Technology presented data on a new membrane microfilter device to capture and characterize circulating tumor cells in blood samples. The device, which separates tumor cells from normal blood cells based on size, captured tumor cells from blood in 92.9% of patients samples, while the current gold standard CellSearch from Johnson & Johnson (New Brunswick, New Jersey) caught the cancer in 45.6% of the samples.
The researchers said the microfilter device is about three to five years from clinical use.
Also working on blood tests to detect cancer is Celera (Alameda, California), which presented data on biomarker panels for the detection of lung, prostate and colon cancer.
Celera said its colon cancer test distinguished proximal and distal lesions with 90% sensitivity and 93% specificity, outperforming the standard fecal occult blood test. In lung cancer, the company's test showed 94% sensitivity and 93% specificity and distinguished malignant cases from benign lung disease.
For now, most cancer biomarkers are used primarily to monitor disease progression and treatment rather than for diagnosis.
Genentech's (South San Francisco, California) Herceptin (trastuzumab) for breast cancer and Novartis AG's Gleevec (imatinib) for chronic myeloid leukemia and gastrointestinal stromal tumors are prescribed according to the results of biomarker-based companion diagnostic tests. Additionally, DxS Ltd. (Manchester, UK) is seeking FDA approval of a companion diagnostic to detect KRAS mutation status in colorectal patients considering Amgen's (Thousand Oaks, California) Vectibix (panitumumab).
Last fall, biomarker data offered new hope for AstraZeneca's (London) EGFR-inhibitor Iressa (gefitinib), which received accelerated approval for lung cancer only to be yanked off the market when it failed to show survival benefit in a confirmatory trial.
A Phase III study of the drug in an enriched population of 1,217 Asian patients expected to be responsive to EGFR inhibitors demonstrated that Iressa monotherapy significantly improved progression-free survival (PFS) compared to chemotherapy in front-line NSCLC patients with EGFR-activating mutations. In patients without the EGFR mutation, the chemotherapy group had significantly better PFS.
So while Iressa couldn't beat placebo in past studies, in the right patients, it beat standard-of-care chemotherapy.
At the AACR conference, several companies presented data from evaluations of drugs in subsets of patients stratified by biomarker analyses.
Ariad Pharmaceuticals (Cambridge, Massachusetts) and partner Merck & Co. (Whitehose Station, New Jersey) presented pre-clinical data showing that their mTOR inhibitor, deforolimus, had anti-tumor activity in models of non-small cell lung cancer with a KRAS mutation. An estimated 20% of NSCLC patients have KRAS mutations, which cause their tumors to be less responsive to EGFR inhibitors like Tarceva (erlotinib, from Genentech and OSI Pharmaceuticals).
Ariad said deforolimus showed better tumor inhibition than Tarceva in 84% of KRAS mutant cell lines tested and inhibited the growth of Tarceva-resistant, KRAS-mutant tumors in multiple mouse models.
Synta Pharmaceuticals (Lexington, Massachusetts) also is focusing on Tarceva-resistant lung cancer. The company said its heat shock protein 90 (Hsp90) inhibitor STA-9090 displayed activity against cell lines expressing seventeen different EGFR mutations associated with NSCLC, including ten mutations that conferred resistance to Tarceva. The molecule also showed activity in cancers resistant to Gleevec (imatinib, from Novartis), Sutent (sunitinib, from Pfizer) and 17-AAG.