RARITAN, NJ – August 6, 2013 - Janssen Diagnostics, LLC announced today that results from the study leading to the approval of CELLSEARCH® in China by that country’s State Food & Drug Administration (SFDA) as an in vitro diagnostic for women with metastatic breast cancer have been published in Annals of Oncology. The study, conducted in China, evaluated the utility of circulating tumor cell (CTC) measurements in predicting responses to anti-cancer therapies and assessed patients across various disease subtypes, including those whose tumors expressed human epidermal growth factor receptor-2 (HER-2). Results demonstrated that enumeration of CTCs utilizing Janssen Diagnostics' CELLSEARCH® system in Chinese women with metastatic breast cancer (MBC) before and after the initiation of standard anti-cancer therapies is a useful predictor of progression-free survival (PFS) and overall survival (OS).
The CELLSEARCH® system is the only CTC test that has obtained U.S. Food and Drug Administration (FDA) 510(k) clearance for aiding in the monitoring of patients with metastatic breast, colorectal or prostate cancer. In addition to its clearance in the United States and approval in China, CELLSEARCH® fulfills the requirements for CE marking in the European Union (EU). CE marking indicates compliance with EU legislation of a product, wherever in the world manufactured, and enables its free movement within the European market.
"This study has shown for the first time the prognostic utility of circulating tumor cells, as detected by CELLSEARCH®, in Chinese women with metastatic breast cancer," said Massimo Cristofanilli, M.D., director of the Jefferson Breast Care Center and one of the study investigators. "The utilization of circulating tumor cells to predict progression-free survival and overall survival will be beneficial to this patient population."
“In China, the incidence of breast cancer has increased rapidly in recent years, in part due to changes in reproductive patterns, obesity, physical inactivity and local breast cancer screening efforts,” said lead study author Zefei Jiang, M.D., Department of Breast Cancer, Affiliated Hospital of Academy of Military Medical Sciences. “These results in HER-2 positive patients are very important since the anti-HER-2 diagnostics and treatment situation in China is different from many parts of the world due to economic constraints and available technology.”
The study, Circulating tumor cells predict progression-free and overall survival in Chinese patients with metastatic breast cancer, HER2-positive or triple-negative (CBCSG004): a multicenter, double-blind, prospective trial, was conducted in 300 measurable MBC Chinese patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 starting a new line of systemic therapy, including any form of endocrine manipulation, cytotoxic chemotherapy or immunotherapy, alone or in combination. The primary objective was to evaluate whether a five CTC cut point (cutoff) is predictive of PFS and OS in this patient population. Approximately 10 mL of blood from each patient was drawn into a 10 mL CellSave Preservative Tube per standard specifications, and CELLSEARCH® was used to detect the number of CTCs in 7.5 mL of whole peripheral blood.
A total of 294 of the 300 patients enrolled between March 2010 and January 2011 from six leading Chinese cancer centers were evaluable. In multivariate Cox regression analyses, the baseline CTC number remained an independent prognostic factor for PFS and OS. Similar results were observed for CTC counts at the first follow-up visit for both PFS and OS.
“This study reinforces data generated from our US clinical trials,” remarked Robert McCormack, Ph.D., head of Technology Innovation at Janssen Diagnostics, LLC. “This agreement in study results obtained more than nine years and almost 7,000 miles apart demonstrates the consistency of CELLSEARCH® performance.”
At baseline, 115 (39.1%) patients had a CTC count of ≥5. These patients had a significantly shorter median PFS (6.7 months; 95% CI = 4.7 to 7.9) and OS (13.2 months; 95% CI = 10.6 to 15.9) compared with patients who had <5 CTC (median PFS = 9.0 months, 95% CI = 7.3 to 11.3, p<0.001; median OS >24.6 months, p<0.001). CTC levels correlated to the sites of metastatic disease, hormone receptor status and human epidermal growth factor receptor 2 (HER-2) status and ECOG performance status.
At first follow-up, patients with a CTC count of <5 (n=178) exhibited a significantly longer median PFS (8.2 vs. 5.9 months; p=0.012) and OS (20.1 vs. 12.4 months; p<0.001) compared to the 49 patients with ≥5 CTC. At the second CTC follow-up, the 39 (16.7%) patients with ≥5 CTC had a significantly shorter median PFS (2.0 months) and OS (9.5 months) than did the 194 patients with a CTC count of <5 (median PFS = 7.6 months, p<0.001; median OS >23.2 months, p<0.001). There were no differences in PFS between those HER-2 positive patients whether or not they received anti-HER-2 treatment at the first follow-up (p=0.622), as well as the second follow-up (p=0.479).
In the subset of triple negative breast cancer (TNBC patients), at both the first and second CTC follow-up visits, those with a CTC count of <5 had significantly longer median PFS (p<0.001 and 0.002) and OS (p=0.003 and <0.001) times compared to those with ≥5 CTC. For all 294 patients, the median PFS and OS were 7.9 months (95% CI = 6.8 to 8.9 months) and 20.9 months (95% CI = 17.3 to >24.8 months), respectively.
About Circulating Tumor Cells
Circulating tumor cells are cancer cells that have detached from the tumor and are found at extremely low levels in the bloodstream. The value of capturing and counting CTCs is evolving as more research data is gathered about the utility of these markers in monitoring disease progression and potentially guiding personalized cancer therapy.
About Janssen Diagnostics
Janssen Diagnostics is the center of excellence in specialized diagnostics development, an important role within the global Janssen pharmaceutical companies. In 1953, founder Dr. Paul Janssen championed an unwavering focus on pharmacological and medical research with a singular objective to improve quality of life by developing medicines that addressed unmet medical needs.
The Janssen Diagnostics team shares that same vision and is dedicated to improving patients' lives, one by one, by making truly personalized care the cornerstone of our healthcare system. Our goal is to influence current thinking beyond drug treatment and develop as a solutions provider. The Janssen legacy of excellence will continue to inspire innovation utilizing real-world data and enable us to reach our goal in developing care solutions that cater to the needs of each individual patient.