On June 4, 2016 Foundation Medicine, Inc. (NASDAQ:FMI) reported new critical genomics data at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2016 demonstrating the clinical significance of comprehensive genomic profiling (CGP) with FoundationOne in identifying patients with advanced lung cancer most likely to respond to RET inhibitor targeted therapies and also to predict those patients likely to develop resistance to targeted therapy (Press release, Foundation Medicine, JUN 4, 2016, View Source [SID:1234513018]).

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Key Data Highlights:

The poster titled, "MDM2 amplification (Amp) to mediate cabozantinib resistance in patients (Pts) with advanced RET-rearranged lung cancers," presented by Romel Somwar, Ph.D., senior research scientist, pathology, Memorial Sloan Kettering Cancer Center, analyzes the genomic profiles of patients treated with the RET inhibitor, cabozantinib, to better understand the molecular mechanisms that underlie intrinsic and secondary resistance. Key study findings include:

Comprehensive genomic profiles were performed on 3,842 lung cancer patients, detecting concurrent MDM2 amplification in 20 percent of tumors with RET fusions
In RET-rearranged cell lines and xenografts treated with cabozantinib and the MDM2 inhibitors, AMG232 and RG7388, a combination of cabozantinib and AMG232 proved more effective at suppressing tumor growth than either agent alone
The study shows that MDM2 amplification is a potential mechanism of primary or acquired resistance to cabozantinib, and therefore MDM2 inhibitors might be studied clinically to prevent the development of acquired resistance and enable longer, more durable responses to treatment
The second poster presentation titled, "Significant systemic and CNS activity of RET inhibitor vandetanib combined with mTOR inhibitor everolimus in patients with advanced NSCLC with RET fusion," by Tina Cascone, M.D., Ph.D. and Vivek Subbiah, M.D., from The University of Texas MD Anderson Cancer Center, demonstrates that targeted combination therapy of vandetanib with the mTOR inhibitor, everolimus, was tolerable and demonstrated significant activity in RET rearranged NSCLC. Key study findings include:

Vandetanib and everolimus were administered to 13 stage IV NSCLC patients, including six patients with tumors harboring RET fusions
All six patients with RET fusions experienced a response, including five partial responses and one patient with stable disease
The six patients with RET fusions were identified using CGP with FoundationOne. Notably, two additional patients tested positive for RET fusions using FISH and did not respond to treatment.
The study suggests that combination therapy was superior to monotherapy with RET inhibitors, warranting further studies of this combination. The study further highlights the superior accuracy of CGP for calling fusions over traditional single gene tests, like FISH.
"By helping us better understand the likelihood of response and resistance to certain therapies, CGP is providing information that can help improve physician treatment decisions and ultimately, we believe, lead to better patient outcomes," said Vincent Miller, M.D., chief medical officer, Foundation Medicine. "Additionally, the sensitivity and accuracy of FoundationOne to reliably detect all classes of clinically relevant alterations in non-small cell lung cancer allow us to circumvent the false positives that often arise with single gene and standard hotspot testing. As this study shows, inaccuracies in genomic testing can lead to unnecessary and often unsuccessful treatments, as well as inefficient and costly care delivery."

Genomic alterations in the RET gene are found in several different types of cancer. RET gene fusions occur in 1 percent of non-small cell lung cancers (NSCLC) and are well-established oncogenic drivers. The RET inhibitor agents, vandetanib and cabozantinib, have demonstrated antitumor activity in NSCLC patients harboring RET fusions, although data suggest that objective responses are observed in only a minority of patients, and progression-free survival (PFS) is shorter than with other oncogene targeted therapies in this disease. A portion of tumors may harbor intrinsic resistance to RET inhibitors, while some respond but eventually progress, yielding to the development of secondary resistance. However, molecular mechanisms that underlie resistance to cabozantinib are poorly understood. Taken together, these studies reinforce the critical importance of FoundationOne in identifying patients likely to respond to targeted therapies and to predict those patients likely to develop resistance.

Lung cancer is by far the leading cause of death among both men and women; about 1 out of 4 cancer deaths are from lung cancer1. There are two major types of lung cancer: NSCLC and small cell lung cancer (SCLC). NSCLC is the most common and accounts for approximately 85 percent of all lung cancer cases2. The American Cancer Society estimates there will be about 224,390 new cases of lung cancer in the United States for 2016 and about 158,080 deaths1.