A new study shows that lapatinib, a drug used for the treatment of metastatic HER2-positive cancer, is associated with improved overall survival in patients with initially HER2-negative metastatic breast cancer and HER2-positive circulating tumor cells (CTCs). This groundbreaking finding was published today in a special issue of the Association for Diagnostics & Laboratory Medicine’s (formerly AACC’s) Clinical Chemistry journal titled “Cancer: Biology & Diagnostics.”
About 10%-20% of all breast cancer tumors express elevated levels of a protein called HER2, which causes cells to divide uncontrollably. These HER2-positive tumors respond well to HER2-targeted therapy. However, the invasive tissue biopsies needed to measure HER2 expression levels in metastatic lesions — which can differ from levels in primary tumors — are not always feasible due to the location of the metastatic site, making it difficult to comprehensively determine HER2 status. Testing the HER2 status of CTCs, which only requires a blood sample, is a promising alternative to invasive biopsy for identifying patients with metastatic cancer who might benefit from HER2-targeted therapy.
In order to assess the feasibility of this approach, the DETECT III trial sought to evaluate the efficacy of HER2-targeted lapatinib therapy for metastatic breast cancer based on a diagnosis of HER2-positive CTCs at the time of metastatic relapse. It is the largest randomized trial to ever address this question. Patients eligible for the trial had metastatic breast cancer not treatable by surgery or radiotherapy alone, as well as HER2-negative tumors and/or lesions and HER2-positive CTCs. Patients received either standard therapy (chemotherapy or endocrine therapy) or standard therapy with lapatinib, and rates of CTC clearance were assessed at various intervals during the trial.
No significant differences were found in CTC clearance rates between the standard and lapatinib arms, regardless of CTCs’ positivity levels and when clearance rates were measured. Patients in the lapatinib arm also showed a modest yet insignificant improvement in progression free survival rates compared to those in the standard arm. Yet remarkably, patients receiving lapatinib had a median survival time of 20.5 months, more than twice as long as patients who underwent standard therapy. The lapatinib-induced boost in overall survivability was observed throughout the length of DETECT III, which spanned over five years.
“DETECT III is the first clinical study indicating that phenotyping of CTCs might have clinical utility for stratification of [metastatic breast] cancer patients to HER2-targeting therapies,” the authors wrote. “CTC-guided therapy may be useful to optimize treatment strategies and should be further investigated in randomized clinical trials.”
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Clinical Chemistry (clinchem.org) is the leading international journal of laboratory medicine, featuring nearly 400 peer-reviewed studies every year that help patients get accurate diagnoses and essential care. This vital research is advancing areas of healthcare ranging from genetic testing and drug monitoring to pediatrics and appropriate test utilization. (VP/Newswise)