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ASCO and the CAP Release Updated Guideline on HER2 Testing in Breast Cancer

The American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) recently issued a joint, updated guideline aimed at improving the accuracy and reporting of human epidermal growth factor receptor 2 (HER2) testing in patients with invasive breast cancer. The guideline update is based on a systematic review of medical research literature, providing oncologists and pathologists with detailed recommendations for how to test for HER2 overexpression, interpret the results, and recommend HER2-targeted therapies. The guideline, originally issued in 2007, is being published in ASCO’s Journal of Clinical Oncology (JCO) and the CAP’s Archives of Pathology & Laboratory Medicine. The joint guideline was prepared by an ASCO/CAP Update Committee consisting of experts in breast cancer and cancer biomarkers.

Cancer Biomarker Study Data Presented at the 2013 AACR Meeting

As we’ve done in previous years here at Biomarker Commons (AACR 2011 and AACR 2012), here’s a roundup of eight research studies on cancer biomarkers that were presented last month at the American Association for Cancer Research (AACR) Annual Meeting in Washington, DC. The theme of this year’s meeting was “Personalizing Cancer Care Through Discovery Science.”

  • Biomarker Analysis Identified Women Most Likely to Benefit From T-DM1

    According to data from a subanalysis of a phase III clinical trial that led the U.S. Food and Drug Administration to approve trastuzumab emtansine (T-DM1) in February, the amount of HER2 in tumors of women with metastatic, HER2-positive breast cancer might determine how much they benefit from the drug. The findings were presented by José Baselga, M.D., Ph.D., physician-in-chief at Memorial Sloan-Kettering Cancer Center in New York.

    Source: AACR

  • Novel Serum Biomarker Bilirubin Predicted Lung Cancer Risk in Smokers

    Researchers from MD Anderson Cancer Center in Houston, Texas, used a unique multiphase study design for the metabolomics profiling of serum samples from non-small lung cancer patients, and showed that bilirubin is a potential biomarker for lung cancer risk prediction. Men who were smokers and had low bilirubin levels had increased risk for cancer incidence and mortality.

    Source: AACR

  • Biomarkers Discovered That May Help Predict Response to Drugs Targeting KRAS-mutated NSCLC

    Massachusetts General Hospital scientists have identified biomarkers that may help predict whether patients with KRAS-mutated non-small cell lung cancer (NSCLC) will respond to concurrent treatment with an MEK inhibitor and a PI3 kinase inhibitor, a drug combination currently being investigated in ongoing clinical trials.

    Source: AACR

  • Screening Blood Samples for Cancer-driving Mutations More Comprehensive Than Analyzing Traditional Tumor Biopsy

    Using a tool called BEAMing technology, which can detect cancer-driving gene mutations in patients’ blood samples, researchers from Dana-Farber Cancer Institute and Harvard Medical School showed that were able to identify oncogenic mutations associated with distinct responses to therapies used to treat patients with gastrointestinal stromal tumors (GIST).

    Source: AACR

  • More Accurate Markers Identified for Detecting Response to Epigenetic Drugs for Myelodysplastic Syndromes

    Researchers from the University of Southern California, Los Angeles, have identified and validated two DNA methylation markers that could help physicians better determine a patient’s response to DNA methyltransferase inhibitors (DNMTi) for the treatment of myelodysplastic syndromes (MDS).

    Source: AACR

  • Cohort Study Indicates That Selenium May Be Protective Against Advanced Prostate Cancer

    According to a data presented by researchers from Maastricht University in the Netherlands, a greater level of toenail selenium is associated with a significant decrease in the risk for advanced prostate cancer.

    Source: AACR

  • Comprehensive Genomic Analysis Identified Alterations in Head and Neck Cancer That Could Lead to Targeted Therapy

    A National Institutes of Health project to catalog the genetic alterations responsible for several types of cancer, in particular those with a poor prognosis, finds that head and neck squamous cell carcinomas are genomically heterogeneous. However, those cancer with certain distinctive patterns could be amenable to specific targeted therapies.

    Source: AACR

  • Novel Drug Combination Showed Antitumor Activity in Patients With Incurable BRCA-deficient Cancers

    Researchers from Dana-Farber Cancer Institute and Harvard Medical School have identified two orally available experimental drugs — sapacitabine and seliciclib — from phase I trial data that, when given sequentially, work together to elicit antitumor effects in patients with incurable BRCA-deficient cancers.

    Source: AACR

Biomarker Analysis Identified Women Most Likely to Benefit From T-DM1

For women with metastatic, HER2-positive breast cancer, the amount of HER2 on their tumor might determine how much they benefit from a drug called trastuzumab emtansine (T-DM1), according to data from a subanalysis of the phase III clinical trial that led the U.S. Food and Drug Administration to approve the drug on Feb. 22, 2013. These findings were presented by José Baselga, M.D., Ph.D., physician-in-chief at Memorial Sloan-Kettering Cancer Center in New York, N.Y., at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10.

“EMILIA was a landmark phase III clinical trial,” said Baselga. “It showed that T-DM1 prolonged progression-free and overall survival for patients with HER2-positive metastatic breast cancer that had been previously treated with trastuzumab and a taxane chemotherapy compared with lapatinib plus capecitabine. Also, it provided proof-of-concept that a new class of drugs called antibody-drug conjugates can benefit patients.”

Antibody-drug conjugates consist of an antibody attached to a toxic chemotherapy, according to Baselga. In the case of T-DM1, the antibody is trastuzumab and the toxic chemotherapy is emtansine. Trastuzumab recognizes the protein HER2, which is found at high levels in HER2-positive breast cancers, and targets the emtansine to the HER2-positive cancer cells, which are killed by the toxic chemotherapy.

In this subanalysis, Baselga and colleagues analyzed tissue samples from patients enrolled in EMILIA to examine whether tumor levels of HER2, as assessed by the amount of HER2 messenger ribonucleic acid (mRNA), affected treatment response. Patients with tumor samples expressing greater than the median amount of tumor HER2 mRNA were considered to have high levels of HER2. Those with tumor samples expressing the median amount of tumor HER2 mRNA or less were considered to have low levels of HER2.

“Even though everyone enrolled in the clinical trial had breast cancer expressing elevated levels of HER2, we know that each person’s tumor has different molecular features,” said Baselga. “Even the degree to which HER2 expression is elevated differs from patient to patient.”

Consistent with the prior analysis, he and his colleagues found that all patients treated with T-DM1 had significantly longer progression-free and overall survival compared with those treated with lapatinib and capecitabine (9.6 months progression-free survival versus 6.4 months; and 30.9 months for overall survival versus 25.1 months).

Patients with tumors expressing higher levels of HER2 derived greater benefit from treatment with T-DM1 compared with patients with tumors expressing lower levels of HER2: Overall survival was 34.1 months for those with high levels of HER2 versus 26.5 months. For patients with tumors expressing higher levels of HER2, those receiving T-DM1 had a 47 percent decreased risk for death compared with those receiving lapatinib and capecitabine.

The researchers also investigated whether tumor mutations in the PIK3CA gene affected treatment response. According to Baselga, patients with PIK3CA-mutated, HER2-positive breast cancer normally do not respond as well to treatment with conventional HER2-targeted therapies such as trastuzumab compared with patients without PIK3CA mutations in their tumors.

However, for patients treated with T-DM1, PIK3CA mutation status did not significantly decrease progression-free survival.

“Our findings are an important step toward identifying the best therapy for individual patients with HER2-positive breast cancer,” said Baselga. “HER2-positive breast cancer is not a uniform disease; each patient is different. These data help us as we look to identify a panel of molecular features that we can use to make informed treatment decisions.”

Kadcyla (ado-trastuzumab emtansine or T-DM1) is a trademark of Genentech, a member of the Roche Group.

Source: American Association for Cancer Research