Foundation Medicine, Inc. and collaborators from the University of Texas MD Anderson Cancer Center and Sarah Cannon Research Institute at HealthOne have announced compelling new data demonstrating that matching patients to targeted therapies based on the unique molecular profile of the patient's advanced cancer leads to improved outcomes across a variety of key measures, including overall survival.
These findings were presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting in a poster titled, "Prospective study comparing outcomes in patients with advanced malignancies on molecular alteration-matched versus non-matched therapy" (abstract # 11019), by Jennifer J. Wheler, M.D., Associate Professor, Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center. In the study, 95% of patients had one or more clinically relevant genomic alterations, demonstrating the potential clinical utility of integrating FoundationOne® comprehensive genomic profiling into clinical practice, and supporting the investigation of this approach in earlier stage disease.
"This study represents one of the first completed prospective trials testing the concept of comprehensive genomic profiling, an important clinical application of next generation sequencing, to match patients to targeted therapies," said Dr. Wheler.
"Despite the fact that these patients had advanced, refractory cancer and were heavily pretreated, the matching of therapy to genomic alterations using this hybrid capture-based NGS approach was independently associated with improvement in all outcome variables," said Razelle Kurzrock, M.D., Chief, Division of Hematology and Oncology, University of California San Diego (UCSD) School of Medicine. "This study establishes that NGS has clinical utility in patients with refractory cancer, and that NGS merits exploration earlier in the disease course." Tumor samples from patients with clinically relevant molecular alterations as identified by FoundationOne were preferentially treated on pathway-matched therapies. A direct match was defined when the drug targeted an alteration or its immediate downstream effector; an indirect match when the drug targeted a protein with more than one effector removed from the alteration. Based on matching and the number of alterations in patients' tumors, an exploratory scoring system was evaluated.
Molecular profiling was performed for 339 patients and, of those, 95% of patients had one or more clinically relevant genomic alterations. Of these patients, 110 patients were treated with a pathway-matched therapy, while 65 patients were treated with a non-matched therapy. Of the patients receiving matched therapy and based on the scoring system, median overall survival of 10.8 months was achieved versus 7.5 months for those patients treated with non-matched therapy. These data provide evidence of the clinical utility of using comprehensive genomic profiling to guide therapeutic choices.
"Mortality rates for patients with advanced, metastatic cancer have until recently gone relatively unchanged over the last three decades, driven largely by a lack of new, FDA-approved therapies for this patient group," said Vincent Miller, M.D., Chief Medical Officer of Foundation Medicine. "The generally low response rate and short progression-free survival common in advanced cancer is indicative of the need for better identification of molecular characteristics associated with potential treatment response and better targeting of treatment in order to achieve higher response rates with less toxicity and adverse side effects. These data validate the positive clinical outcomes resulting from comprehensive genomic profiling and further support the need for reimbursement, enabling patient access to this critical component in modern cancer care."