On March 24, 2016 Foundation Medicine, Inc. (NASDAQ:FMI) reported the publication of two manuscripts that underscore the importance of integrating comprehensive genomic profiling with FoundationOne into the management of patients with advanced lung cancer (Press release, Foundation Medicine, MAR 24, 2016, View Source [SID:1234509914]). Data from these studies demonstrate that comprehensive genomic profiling enabled identification of cancer-driving alterations that were or would have been missed by narrow, more limited hotspot testing. In both studies, researchers concluded that the discordant findings of the testing approaches underscore the fact that comprehensive genomic profiling consistently provides non-small cell lung cancer patients with more accurate and a broader range of treatment options, including clinical trials, versus narrow hotspot tests.

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Findings from the two studies were published in Oncotarget and Clinical Cancer Research.

"Targeted therapies have revolutionized the treatment of lung cancer; however, for such therapies to be optimally matched to the right patients, there is an inherent mandate for comprehensive, highly accurate and sensitive clinical testing that can detect all actionable genomic alterations," said Mohamed Mohamed, M.D., Ph.D., co-director of the Thoracic Oncology Program, Cone Health Cancer Center in Greensboro, NC and co-author of the study published in Clinical Cancer Research. "Taken together, these studies reveal the inherent limitations of single-gene or hotspot testing, which fail to characterize the entire coding regions of cancer genes and detect all four classes of genomic alterations, thereby missing targeted therapy options that are often clinically relevant for treatment of advanced cancer."

Lung cancer is the leading cancer killer in both men and women in the United States1. An estimated 159,260 Americans died from lung cancer in 2014, accounting for approximately 27 percent of all cancer deaths2. There are two major types of lung cancer: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC is the most common and accounts for approximately 85 percent of all lung cancer cases3. Adenocarcinoma is the most common subtype of NSCLC.

"These studies demonstrate the clinical utility and the opportunity for improved clinical outcomes achieved by integrating comprehensive genomic profiling into clinical care for advanced non-small cell lung cancer," stated Byoung Chul Cho, M.D., Ph.D., associate professor, division of medical oncology, Yonsei Cancer Center and Department of Internal Medicine, Yonsei University College of Medicine in Korea and senior author of the study published in Oncotarget.

Key Findings Published in Oncotarget

The article, entitled "Genomic Profiling of Lung Adenocarcinoma Patients Reveals Therapeutic Targets and Confers Clinical Benefit When Standard Molecular Testing is Negative," was published online in the journal Oncotarget and demonstrates that maximally identifying actionable genomic alterations in advanced lung cancer patients is an important factor in improving clinical outcomes. Comprehensive genomic profiling using FoundationOne was performed on tumor specimens from 51 patients with advanced lung adenocarcinomas, which previously tested negative for the known driver oncogenes EGFR, KRAS and ALK. Key study findings include:

31 percent of patients harbored clinically relevant genomic alterations that were not previously discovered by the prior clinical testing.

A genomic alteration with a corresponding targeted therapeutic based on the National Comprehensive Cancer Network (NCCN) guidelines was identified in 39 percent of patients. This data supports a previous finding by Drilon et al4 showing 26 percent of previously negative NSCLC patients harbored a genomic alteration with a corresponding targeted therapy in NCCN guidelines.

Genomic alterations for which clinical trials of targeted therapies could be considered were discovered in an additional 27 percent of patients. Similarly, in the study referenced above, Drilon et al demonstrated that 39 percent of NSCLC patients enrolled in that study harbored genomic alterations that could be linked to a clinical trial at the principal investigator’s cancer center.

Seven patients with ROS1 rearrangements were enrolled in an ongoing trial assessing ceritinib, an inhibitor of activated ROS1. All but one of the patients who received ceritinib experienced objective responses.
Key Findings Published in Clinical Cancer Research

The article, entitled "Comprehensive Genomic Profiling Identifies Frequent Drug Sensitive EGFR Exon 19 Deletions in NSCLC Not Identified by Prior Molecular Testing," was published online in Clinical Cancer Research and highlights the importance of using comprehensive genomic profiling in advanced NSCLC to allow for sensitive detection of clinically relevant mutations. From a larger series of NSCLC cases assayed with FoundationOne in the course of clinical care, 400 consecutive cases harboring EGFR ∆ex19 deletions were reviewed. Key study findings include:

Pathology reports for 250 NSCLC cases harboring classic EGFR ∆ex19 deletions identified by comprehensive genomic profiling were systematically reviewed. Of these, previous EGFR test results were available for 71 cases, and 17 percent had previously tested negative for EGFR mutation.

In a subset of these patients with available clinical outcome information, treatment benefit with EGFR inhibitors was observed with EGFR TKI therapy.

Of 14 NSCLC cases with an EGFR ∆ex19 C-helical deletion, previous non-hybrid capture based EGFR sequencing results were available for six cases, and of these cases, five (83 percent) had negative prior testing.

"These studies show the discordant results between narrow sequencing and comprehensive genomic profiling with FoundationOne, implying that potentially clinically actionable targets may only be reliably detected when comprehensive genomic profiling is incorporated into clinical care," said Vincent Miller, M.D., chief medical officer, Foundation Medicine and co-author of the study. "As a result, advanced stage lung cancer patients are losing precious time with multiple rounds of hot spot and limited sequencing tests and ultimately, potentially missing critical opportunities to benefit from approved targeted therapies and clinical studies. We continue to provide evidence validating care efficiencies and clinical value that can be realized through use of our comprehensive genomic profiling approach at initial diagnosis of advanced lung cancer."