FoundationOne® Identifies Patients with Advanced Lung Cancer Likely to Respond or Develop Resistance to Certain RET Inhibitor Therapies
Data Underscore the Value of Molecular Information to Enable Informed Therapeutic Choices, Improved Outcomes and Efficient Clinical Care
Key Data Highlights:
The poster titled, "MDM2 amplification (Amp) to mediate cabozantinib resistance in patients (Pts) with advanced RET-rearranged lung cancers," presented by
- 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
- 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
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
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Cautionary Note Regarding Forward-Looking Statements for
This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding the ability of comprehensive genomic profiling, including FoundationOne, to identify genomic alterations; the ability of certain genomic alterations to predict whether a patient will respond to targeted therapies or develop resistance to targeted therapies and the longevity of response; the accuracy of comprehensive genomic profiling compared to other tests; the ability of FoundationOne to inform therapeutic choices and improve patient outcomes; and the relevance of comprehensive genomic profiling in oncology clinical care, including the ability to increase efficiencies in clinical care. All such forward-looking statements are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include the risk that the results presented are found to lack scientific, medical or clinical utility or that subsequent research renders the results presented less useful or not useful in clinical practice; Foundation Medicine's services and molecular information platform will not be able to identify genomic alterations in the same manner as prior clinical data; and the risks described under the caption "Risk Factors" in
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2 U.S. National Institutes of Health. National Cancer Institute: SEER Cancer Statistics Review, 1973-2006.
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