New evidence of important role of next-generation sequencing in cancer treatment

Foundation Medicine, Inc., a molecular information company that brings comprehensive cancer genomic analysis to routine clinical care, today announced results from two studies using next-generation sequencing (NGS) to provide actionable information about genomic tumor alterations in individual patients' cancers across all solid tumor types. The studies, being presented this week in an oral and poster session at the 2012 Annual Meeting of the American Society of Clinical Oncology (ASCO), provide new evidence of the important role and clinical impact of NGS in cancer treatment.

“One test, using a very small amount of tissue, can enable physicians to tailor treatment to a patient's molecular subtype. With our pan-cancer genomic profile now commercially available, physicians will have a critical decision-making tool to assist them in making the most appropriate therapeutic choices for their patients with cancer.”

These data follow Foundation Medicine's recent launch of FoundationOne™, the first pan-cancer, fully informative genomic profile for all solid tumors.

"These studies, along with other results previously presented and published, provide unequivocal evidence of the significant clinical value of NGS-based comprehensive genomic analysis," said Michael J. Pellini, president and chief executive officer, Foundation Medicine. "One test, using a very small amount of tissue, can enable physicians to tailor treatment to a patient's molecular subtype. With our pan-cancer genomic profile now commercially available, physicians will have a critical decision-making tool to assist them in making the most appropriate therapeutic choices for their patients with cancer."

The first study, "Discovery of Recurrent KIF5B-RET Fusions and Other Targetable Alterations from Clinical NSCLC Specimens" (Abstract # 7510), was completed in collaboration with researchers at Dana-Farber Cancer Institute and assayed cancer-relevant genes in 24 cases of non-small cell lung cancer (NSCLC). Highlights of the analysis include:

• 50 genomic alterations in 21 genes were identified using NGS, with at least one relevant alteration occurring in 83 percent of tumors.
• In 72 percent of the samples, at least one genomic alteration was associated with an available treatment or clinical trial of a targeted therapy.
• Researchers discovered a novel, recurrent KIF5B-RET gene fusion, which occurred in tumors lacking all other known oncogenic driver alterations. KIF5B-RET, when introduced into Ba/F3 cells, showed IL-3 independent growth consistent with oncogenic transformation.
• Preliminary sensitivity findings suggest that clinical trials are warranted to investigate the effect of multi-kinase inhibitors that inhibit RET (sunitinib, sorafenib and vandetinib) on tumors harboring the KIF5B-RET fusion.

"Many non-small cell lung cancers have oncogenic alterations that may be sensitive to a targeted therapeutic approach, which can lead to better outcomes for individual patients," said Marzia Capelletti, Ph.D., Research Fellow in Medicine, Dana-Farber Cancer Institute. "The challenge for physicians is to comprehensively understand the patient's cancer by characterizing the genomic profile and develop a rational treatment strategy. The results of this study clearly demonstrate that there is a need to have a reliable tool to identify the particular molecular drivers of a tumor to help select appropriate therapies for individual patients."

An additional study, "Next-Generation Sequencing Reliably Identifies Actionable Genomic Changes in Common and Rare Solid Tumors: The FMI Experience with the Initial 50 Consecutive Patients" (Abstract #10590), utilized NGS to identify actionable genomic alterations across a variety of solid tumors in the first 304 clinical specimens (poster updated with clinical experience through May 1, 2012) analyzed by Foundation Medicine's CLIA-approved laboratory. Alterations were defined as actionable if linked to an approved therapy in the tumor under study or another solid tumor; a known or suspected contraindication to a given therapy; or a clinical trial linked to the alteration. Lung, breast, colorectal, ovarian and pancreatic cancers were the most common solid tumors identified among 16 primary tumor types. In the analysis:

• Investigators reported that of 304 samples analyzed, 292 were successfully reported, for a failure rate of only 4%.
• Of the reported samples, 77% (224/292) had at least one actionable alteration.
• Additionally, 59% (172/292) had at least one actionable alteration that would not have been detected by commonly available molecular assays.
• Among the reported samples in the three most common tumor types, 52/61 lung samples (85%), 43/50 breast samples (86%), and 28/31 colon samples (90%) had at least one actionable alteration.
• There were a total of 193 unique actionable alterations found in this data set.

"The complex nature of cancer and the transformation of cancer care, prompted by advanced understanding of genomic subtypes and emergence of targeted therapies, make the detection of alterations to guide therapeutic decision-making more critical than ever," said Gary Palmer, M.D., J.D., M.P.H., senior vice president of medical affairs and commercial development, Foundation Medicine, and lead author of the study. "This NGS assay makes it possible for clinicians to make the best possible therapeutic choices, minimize the use of ineffective therapies and enhance enrollment in clinical trials appropriate for the individual patient."

Foundation Medicine's first commercial offering, FoundationOne, is a fully informative genomic profile that allows any oncologist to use the same technology that informed the studies presented here as a clinical decision making tool in their own practice. FoundationOne uses routine, formalin-fixed, paraffin-embedded tumor samples. Test results are provided in a straightforward report that matches detected patient's genomic alterations with potential treatment options and clinical trials.