A Blood-Based Test for EGFR Mutations in NSCLC Is Being Developed

“Clovis Oncology is evaluating a blood-based assay to detect EGFR mutations in circulating tumor DNA in non-small cell lung cancer patients as a way to better identify candidates for treatment with rociletinib (CO-1686), its investigational EGFR inhibitor, a Clovis scientist said this week.

“During a talk at the Cambridge Healthtech Institute Molecular Medicine Tri-Conference held here, Chris Karlovich, principal scientist for molecular diagnostics at Clovis, said that his company is comparing the performance of Sysmex Inostics’ BEAMing assay service to that of Qiagen’s TheraScreen EGFR PCR test in a subset of patients from the company’s “third-generation inhibitor of mutant EGFR lung cancer” (TIGER) clinical trial for rociletinib.

“The goal, Karlovich said, is to overcome some of the limitations of tissue-based PCR testing in identifying EGFR mutations, particularly the T790M resistance mutation, which can be used to identify patients who have become resistant to EGFR-directed therapy and thus are candidates for second- or later-line treatment with rociletinib. In addition, Karlovich said, blood-based assays like BEAMing could potentially be used to more easily monitor response to the drug.

“Rociletinib was designed to selectively target initial activating EGFR mutations and the T790M resistance mutation, while sparing wild-type EGFR at anticipated therapeutic doses, with an improved toxicity profile, according to Clovis’ website.”


70-Gene Signature Not Cost-Effective in Breast Cancer

The gist: Doctors sometimes use molecular tests to help make treatment decisions. These tests give information about the genetics of a patient’s tumor. Different companies make different kinds of molecular tests for patients with node-negative breast cancer (NNBC). These tests help with decision-making for adjuvant chemotherapy—chemotherapy after tumor-removal surgery to keep the cancer from returning. Recently, scientists found that one of these tests was not cost-effective when compared to other options.

“For patients with node-negative breast cancer (NNBC), the 70-gene signature is unlikely to be cost-effective for guiding adjuvant chemotherapy decision making, according to a study published online Oct. 6 in the Journal of Clinical Oncology.

“Julia Bonastre, Ph.D., from Gustave Roussy in Villejuif, France, and colleagues conducted an economic analysis of the 70-gene signature used to guide adjuvant chemotherapy decision making in patients with NNBC. The 70-gene signature was compared with Adjuvant! Online and chemotherapy in all patients as a basis for the decision to administer adjuvant chemotherapy. Costs, life-years (LYs), and quality-adjusted life-years (QALYs) were compared over a 10-year period.

“The researchers observed similar mean differences in LYs and QALYs for the three strategies. Higher cost was seen in association with the 70-gene strategy, with a mean difference of €2,037 and €657 compared with Adjuvant! Online and systematic chemotherapy, respectively. The probability of being the most cost-effective strategy was 92 percent for Adjuvant! Online, 6 percent for systematic chemotherapy, and 2 percent for the 70-gene signature, for a €50,000 per QALY willingness-to-pay threshold.

” ‘Optimizing adjuvant chemotherapy decision making based on the 70-gene signature is unlikely to be cost-effective in patients with NNBC,’ the authors write.


Drug Shows Promise for Subset of Stage III Colon Cancer Patients

This article describes the results of a clinical trial—a research study with volunteer patients. The trial tested adding a third drug to a standard two-drug chemotherapy treatment for colorectal cancer. The standard treatment consists of the drugs fluorouracil and leucovorin. It is given to patients after tumor-removal surgery to keep the cancer from coming back (recurrence). In the trial, a third drug called irinotecan was added. The researchers found that stage III patients whose tumors tested positive for a genetic change called CIMP benefitted from the irinotecan addition. Stage III CIMP-negative patients did not.

“When added to the standard chemotherapy treatment — fluorouracil and leucovorin — adjuvant irinotecan therapy improved overall survival rates for patients with the CpG island methylator phenotype (CIMP). CIMP is seen in about 10 to 20 percent of colorectal cancers. Patients with CIMP-negative tumors, however, exhibited significant harm from the addition of irinotecan — overall survival was 68 percent compared with 78 percent for those receiving the standard treatment alone.

“Our results serve as an example that the molecular characterization of individual tumors may help to determine the most appropriate treatment for patients with colon cancer,” said lead study author Stacey Shiovitz, MD, from the department of medicine, University of Washington, Seattle, WA, and the clinical research division of Fred Hutchinson Cancer Research Center, also in Seattle. “Based on our findings, identification of a tumor’s CIMP status should play a greater role in the clinical setting.”