Tag Archives: US Oncology

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TGen-TD2-Scottsdale Healthcare study benefits patients

The Side-Out Foundation’s breast cancer pilot study, led by the Translational Genomics Research Institute (TGen), Translational Drug Development (TD2) and Scottsdale Healthcare, has shown that cancer patients do better when their treatment is guided by molecular profiling.

Specifically, 52 percent of patients with advanced breast cancer received clinical benefit – meaning their disease was controlled for a longer time – when their cancer was treated based on addressing the abnormal proteins in their tumor, according to the study conducted at the Virginia G. Piper Cancer Center Clinical Trials, a partnership of Scottsdale Healthcare and TGen.

Each patient’s treatment was “personalized,” meaning that the therapy they received was based on their individual tumor biology.

“This study demonstrates the feasibility of personalized cancer treatment, and shows that this approach merits further investigation in future studies,” said Gayle Jameson, Nurse Practitioner at Scottsdale Healthcare’s Virginia G. Piper Cancer Center Clinical Trials and the study’s Principal Investigator.

“The success of this pilot study will lead to a larger study and hopefully greater clinical benefit for more patients with advanced breast cancer,” said Jameson, who presented the results of the study in June at the 2013 American Society of Clinical Oncology (ASCO) in Chicago.

Due to the overwhelmingly positive results, a new study incorporating additional technology for tumor analysis, Side-Out II, will open at the Virginia G. Piper Cancer Center Clinical Trials in the near future for patients with advanced breast cancer.

“The success of our pilot proof-of-concept study has established a firm launching pad for the upcoming Side-Out II study, which involves a more in-depth investigation of tumor biology with an expanded repertoire of tests to direct personalized treatment,” said Dr. Jasgit Sachdev, M.D., a breast cancer specialist and Associate Professor at the Virginia G. Piper Cancer Center Clinical Trials.

“By showing the significant advantages of molecular profiling, this pilot study has enabled us to move forward with a project that should strengthen the evidence for using this approach in routine clinical care.”

The recent pilot study built on previous studies by Scottsdale Healthcare and TGen that showed the value of guiding treatment based on molecular profiling, in which each patient’s tumor was analyzed for protein abnormalities that may “drive” the cancer’s growth. The results pointed investigators toward specific genetic changes that might be addressed by specific medications.

Beyond molecular profiling, the pilot study also included mapping proteomic pathways within the tumor tissue so each patient could receive a highly targeted regimen designed to impede their cancer growth.

All of the patients in the recent study had advanced breast cancer that had progressed following multiple previous chemotherapy treatments. Of the 25 patients, 13 received clinical benefit as a result of molecular profiling. For all 25 patients, the therapy selected based on their tumor analysis was different than what they would have received in their next planned treatment, if they had not participated in the study.

The Virginia G. Piper Cancer Center at Scottsdale Healthcare was the lead site in the 2-½ year pilot study. In addition, patients in the study were treated at Virginia Cancer Specialists, US Oncology, in Fairfax, Vir.; and at Evergreen Hematology & Oncology in Spokane, Wash.

Translational Drug Development (TD2), a TGen company, managed the pilot clinical trial, and will also oversee the follow-on study, Side-Out II.

“This was an exciting study for TD2,” said Linda Vocila, BSN, RN, Director of Clinical Operations at TD2 and co-author of the study. “It demonstrates that close collaboration between physicians and scientists leads to greater clinical benefit for patients with cancer.”

Two labs analyzed tissue: the Center for Applied Proteomics and Molecular Medicine (CAPMM) at George Mason University in Manassas, Vir.; and Caris Life Sciences in Phoenix.

The Side-Out Foundation of Fairfax, Vir., sponsored the study.

To participate in a clinical trial at the Virginia G. Piper Cancer Center, please contact Patient Care Coordinator Joyce Schaffer at 480-323-1339 or joschaffer@shc.org.

medical.research

TGen-US Oncology data helps triple-negative breast cancer patients

Genomic sequencing has revealed therapeutic drug targets for difficult-to-treat, metastatic triple-negative breast cancer (TNBC), according to an unprecedented study by the Translational Genomic Research Institute (TGen) and US Oncology Research.

The study is published by the journal Molecular Cancer Therapeutics and is currently available online.

By sequencing, or spelling out, the billions of letters contained in the genomes of 14 tumors from ethnically diverse metastatic TNBC patients, TGen and US Oncology Research investigators found recurring significant mutations and other changes in more than a dozen genes. In addition, the investigators identified mutations previously unseen in metastatic TNBC and took the sequencing data into account in selection of therapeutic protocols specific to each patient’s genetic profile.

“This study stands as a one-of-a-kind effort that has already led to potentially beneficial clinical trials, and sets the stage for future investigations,” said Dr. John Carpten, Ph.D., TGen’s Deputy Director of Basic Science and Director of TGen’s Integrated Cancer Genomics Division, and the study’s senior author.

The most frequently mutated gene among the tumors (seven of 14) was the TP53 tumor suppressor, and aberrations were observed in additional tumor suppressor genes including CTNNA1, which was detected in two of six African American patients (who typically have more aggressive and treatment-resistant disease). Alterations were also seen in the ERBB4 gene, known to be involved in mammary-gland maturation during pregnancy and lactation, but not previously linked to metastatic TNBC.

The study included an “outlier analysis,” which assessed expression patterns for each tumor when compared against the other tumors examined in the study. Specific cancer genes overexpressed among tumors in the study’s cohort included: ALK, AR, ARAF, BRAF, FGFR2, GLI1, GLI2, HRAS, HSP90AA1, KRAS, MET, NOTCH2, NOTCH3, and SHH. Significantly underexpressed cancer genes included: BRCA1, BRCA2, CDKN2A, CTNNA1, DKK1, FBXW7, NF1, PTEN, and SFN.

Each tumor was genomically unique, but nine of the 14 contained alterations in one or both of two particular cellular pathways: RAS/RAF/MEK/ERK and PI3K/AKT/MTOR.  Targeted therapeutic intervention aimed at these pathways achieved impressive responses in several cases.

“Importantly, the analysis provided insights into the potential unique therapeutic vulnerabilities of each cancer,” said Dr. Joyce O’Shaughnessy, M.D., the study’s other co-lead author. Dr. O’Shaughnessy is a practicing oncologist with Texas Oncology — an affiliate of The US Oncology Network — and is the Celebrating Women Chair of Breast Cancer Research at Baylor Charles A. Sammons Cancer Center.

Metastatic TNBC is a highly aggressive form of breast cancer that disproportionately affects African-Americans. It is called triple-negative because tumors do not express the estrogen receptor, progesterone receptor or HER-2, the biomarkers successfully targeted in most breast cancers.

Metastatic TNBC also has a poor prognosis once the cancer has spread to other organs, with a median survival rate among metastatic patients of only one year. While TNBC accounts for only about 15 percent of all breast cancers, its more aggressive biology makes it responsible for nearly one in four deaths related to this disease.

“The nature of this disease cries out for innovative research techniques such as whole genome sequencing coupled with new tools for data analysis,” said Dr. David Craig, Ph.D., TGen’s Deputy Director of Bioinformatics, and one of the study’s co-lead authors.

“We are aware that these results are preliminary and based on a small series of patients,” said Carpten. “However, our study will pave the way for new clinical trials and novel hypotheses for future testing in a very difficult to treat cancer.”

Whole-genome sequencing of tumors and normal tissue was performed on Life Technologies Corporation’s Applied Biosystems SOLiD™ 4.0 platform, and results were validated in a CLIA-certified laboratory.

The study, “Genome and transcriptome sequencing in prospective triple negative breast cancer uncovers therapeutic vulnerabilities,” is sponsored by the Translational Genomics Research Institute (TGen) and US Oncology Research with support from Life Technologies Corporation.

Molecular Cancer Therapeutics is one of several peer-reviewed scientific journals published by the 34,000-member American Association for Cancer Research (AACR), the oldest and largest scientific organization in the world focused on every aspect of high-quality, innovative cancer research. The programs and services of the AACR foster the exchange of knowledge and new ideas among scientists dedicated to cancer research, provide training opportunities for the next generation of cancer researchers, and increase public understanding of cancer.