Importance of Genomic Profiling in Lung Cancer

From the late 1990’s to present, the number of known, targetable genomic drivers of NSCLC has rapidly increased. It is now widely accepted that cancer is a disease of the genome, and that genomically driven targeted treatment is often more effective and less toxic than traditional chemotherapy.

Comprehensive genomic profiling is essential in choosing targeted therapies based on the patient’s unique tumor profile.

Modified and updated from Pao and Hutchinson, Nature Medicine. 2012; 18:349-351.

About FoundationOne®

FoundationOne is a comprehensive and fully informative genomic profile that identifies all clinically relevant genomic alterations that are driving the growth of a patient’s cancer. It helps physicians to precisely identify targeted treatment options that may not have been otherwise considered.

FoundationOne interrogates the entire coding sequence of 315 cancer-related genes plus select introns from 28 genes often rearranged or altered in solid tumor cancers.

Why FoundationOne?

FoundationOne is a comprehensive genomic profiling assay that can identify 3X more targeted therapy options for your patients compared to hotspot panel tests. The rigorous analytic validation of the assay has been published in the prestigious journal, Nature Biotechnology. FoundationOne is also the chosen clinical assay for groundbreaking collaborative initiatives such as the LungMAP trial and The Genomics of Young Lung Study.

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Comprehensive genomic profiling is changing the way that cancer is being treated and is designed to help you ensure that all available treatment options are considered for your patients.

To fully realize the potential of genomic testing, particularly in lung cancer, comprehensive genomic profiling should be incorporated into patient management. We need to look beyond the hotspot approach that focuses only on detecting high frequency genomic alterations or individual gene test approaches which consumes precious tissue without providing a comprehensive picture.

Watch this video to learn about the fundamental difference between FoundationOne’s approach and hotspot NGS panels to understand how a truly comprehensive approach can benefit your patients.

FoundationOne matches all clinically relevant alterations identified to targeted therapies and clinical trials based on current scientific evidence and published clinical data.

This information is presented in the form of an easy-to-read and fully informative report to physicians. Clear, potentially actionable results are presented on the front page of the report enabling oncologists to make better informed treatment decisions. Detailed information regarding supporting evidence and clinical data is also provided for reference. Here is a preview of the first page of a sample report.

All of your patient reports are available online with links to current research and clinical trials. Watch this video to learn more about Interactive Cancer Explorer™, our online portal to access patient reports.

According to a recent study presented at ASCO 2014, FoundationOne identified clinically relevant genomic alterations in 65% of NSCLC patients who tested negative after extensive standard panel testing

  • 26% (n=8/31) of patients had genomic alterations for which there was a targeted therapy in NCCN guidelines
  • 39% (n=12/31) of patients had genomic alterations for which there was a targeted therapy available on or off of a clinical trial
  • 29% (n=9/31) of patients had a genomic alteration for which there was no targeted therapy currently available
  • Of all patients in this study, only 6% (n=2/31) had no genomic alterations identified

There are four different classes of cancer-causing, clinically relevant genomic alterations including

  • base pair substitutions
  • insertions/deletions
  • copy number alterations
  • rearrangements

Standard single-marker tests such as FISH and IHC, and hotspot panels are typically able to identify just one or two classes of clinically relevant alterations.

FoundationOne has been demonstrated to identify all of these classes of clinically relevant alterations with higher accuracy than traditional, standard of care testing. FoundationOne can identify up to 3X more targeted therapy options for your patients compared to hot spot panels.

Click on the arrow to review our clinical utility data

*In a recent study, FoundationOne identified ALK fusions that were previously missed by FISH testing, giving these patients access to therapy they would likely benefit from but would not have otherwise received.

(9/28) of ALK-rearranged cases (as identified by FoundationOne) in which FISH testing for ALK-rearrangements had been done tested negative by FISH

of the FISH-negative patients (5 out of 7) from this study treated with crizotinib responded positively confirming that the ALK rearrangements detected by FoundationOne, and missed by the Vysis FISH test, were indeed acting as oncogenic drivers

Supporting Data

Multicenter ALK testing in Non-Small-Cell Lung Cancer: Results of a Round Robin Test
von Laffert, Maximilian; Penzel, Roland; Schirmacher, Peter; Warth, Arne; Lenze, Dido; Hummel, Michael; Dietel, Manfred

NSCLC tissue specimens, or biopsies, can be small and difficult to obtain. Often biopsies are collected as fine needle aspirates. Extracting all clinically relevant information is difficult and sometimes impossible using single marker tests and/or hotspot panels due to the lack of precious tissue.

Comprehensive genomic profiling with FoundationOne avoids the need for multiple single-marker or hotspot tests and thereby conserves precious tissue and saves time. It also requires only a small amount of tissue to get a comprehensive profile of the cancer.

Click here to download FoundationOne Sample requirements Click here to view our published study on successful comprehensive genomic profiling from FNA samples.

The FoundationACCESS program is aimed to help patients and physicians access FoundationOne and targeted therapies.

Through the FoundationACCESS program, Foundation Medicine offers specialized and individualized services to help patients navigate through the billing and reimbursement process as well as enabling access to targeted therapies and clinical trials that are recommended. Learn more about our FoundationACCESS program here.


FoundationOne identified a novel crizotinib-sensitive ALK rearrangement in a patient with metastatic non-small-cell lung cancer.

Case presentation
A 43-year-old male never-smoker presented with pericardial tamponade. Pericardio/thoracentesis yielded 2.5 liters of fluid; light microscopy was consistent with lung adenocarcinoma. No epidermal growth factor receptor (EGFR) mutation or EML4-ALK rearrangement was detected. After talc pleurodesis, he was begun on pemetrexed and cisplatini, which was poorly tolerated and he experienced disease progression after 4 cycles of therapy.
Molecular testing
EGFR testing was negative. FISH testing was negative using standard criteria. However, FoundationOne comprehensive genomic profiling revealed an EML4-ALK fusion.
On the basis of these results, the patient was treated with crizotinib. Significant improvement was seen after 4 months, the positron emission tomography scan became negative and the chest computed tomography scan showed further shrinkage of the primary lesion (Response Evaluation Criteria in Solid Tumors -75% reduction).
ALK gene fusions occur in 2% to 7% of non-small cell lung cancer cases and these tumors are commonly sensitive to crizotinib. These rearrangements are not reliably detected by the Break-Apart FISH assay. FoundationOne revealed the clinically relevant alterations in order to tailor the treatment approach.

Identification of novel TRIM33-RET fusion in a non-small cell lung cancer patient.

Case presentation
Middle aged female, never-smoker diagnosed with stage IV – B lung adenocarcinoma.
Molecular testing
Extensive panel based testing was negative. Including a PCR-based for a KIF5B-RET fusion. FoundationOne identified a TRIM33 – RET fusion.
The patient was enrolled in a phase II study of cabozantinib after progression on 2 prior lines of cytotoxic chemotherapy therapy. Follow-up imaging conducted after 4 and 12 weeks of therapy revealed a confirmed partial response with a 66% decrease in measurable disease in the lungs and pleura by Response Evaluation Criteria in Solid Tumors (RECIST).
Investigators at Memorial Sloan Kettering Cancer Center initiated this prospective trial of cabozantinib in July 2012, within only a few months of the publication of RET fusions in lung adenocarcinoma in late 2011. This illustrates how a rapid bench-to-bedside process allows for accelerated drug development when coupled with comprehensive genomic profiling of tumor specimens.
Foundation Medicine publications in lung cancer
  1. Next-Generation Sequencing Reveals a Novel NSCLC ALK F1174V Mutation and Confirms ALK G1202R Mutation Confers High-Level Resistance to Alectinib (CH5424802/RO5424802) in ALK-Rearranged NSCLC Patients Who Progressed on crizotinib. Ou SH, Azada M, Hsiang DJ, Herman JM, Kain TS, Siwak-Tapp C, Casey C, He J, Ali SM, Klempner SJ, Miller VA. J Thorac Oncol. 2014 Apr;9(4):549-53. PMID: 24736079.
  2. Acquired Resistance of EGFR-Mutant Lung Adenocarcinomas to Afatinib plus Cetuximab Is Associated with Activation of mTORC1. Pirazzoli V, Nebhan C, Song X, Wurtz A, Walther Z, Cai G, Zhao Z, Jia P, de Stanchina E, Shapiro EM, Gale M, Yin R, Horn L, Carbone DP, Stephens PJ, Miller V, Gettinger S, Pao W, Politi K. Cell Rep. 2014 May 22;7(4):999-1008. Epub 2014 May 9. PMID: 24813888.
  3. Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer. Vaishnavi A, Capelletti M, Le AT, Kako S, Butaney M, Ercan D, Mahale S, Davies KD, Aisner DL, Pilling AB, Berge EM, Kim J, Sasaki H, Park SI, Kryukov G,Garraway LA, Hammerman PS, Haas J, Andrews SW, Lipson D, Stephens PJ, Miller VA, Varella-Garcia M, Jänne PA, Doebele RC. Nat Med. 2013 Oct 27. [Epub ahead of print]
  4. Clinical next-generation sequencing successfully applied to fine-needle aspirations of pulmonary and pancreatic neoplasms. Young G, Wang K, He J, Otto G, Hawryluk M, Zwirco Z, Brennan T, Nahas M, Donahue A, Yelensky R, Lipson D, Sheehan CE, Boguniewicz AB, Stephens PJ, Miller VA, Ross JS. Cancer Cytopathol. 2013 Jun 24. [Epub ahead of print]
  5. Next-Generation Sequencing Reveals High Concordance of Recurrent Somatic Alterations Between Primary Tumor and Metastases From Patients With Non-Small-Cell Lung Cancer Vignot S, Frampton GM, Soria JC, Yelensky R, Commo F, Brambilla C, Palmer G, Moro-Sibilot D, Ross JS, Cronin MT, André F, Stephens PJ, Lazar V, Miller VA, Brambilla E. Journal of Clinical Oncology. 2013 April 29.
  6. Response to Cabozantinib in Patients with RET Fusion-Positive Lung Adenocarcinomas Drilon A, Wang L, Hasanovic A, Suehara Y, Lipson D, Stephens PJ, Ross J, Miller VA, Ginsberg MS, Zakowski MF, Kris MG, Ladanyi M, Rizvi NA. Cancer Discovery. 2013 Mar 26. [Epub ahead of print]
  7. Next Generation Sequencing Identifies and Immunohistochemistry Confirms a Novel Crizotinib Sensitive ALK Rearrangement in a Patient with Metastatic Non-small Cell Lung Cancer Peled N, Palmer G, Hirsch FR, Wynes MW, Ilouze M, Varella-Garcia M, Soussan-Gutman L, Otto GA, Stephens PJ, Ross JS, Cronin MT, Lipson D, Miller VA. J Thoracic Oncology. 2012 Sep.
  8. Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies Lipson D, Capelletti M, Yelensky R, Otto G, Parker A, Jarosz M, Curran JA, Balasubramanian S, Bloom T, Brennan KW, Donahue A, Downing SR, Frampton GM, Garcia L, Juhn F, Mitchell KC, White E, White J, Zwirko Z, Peretz T, Nechushtan H, Soussan-Gutman L, Kim J, Sasaki H, Kim HR, Park SI, Ercan D,Sheehan CE, Ross JS, Cronin MT, Jänne PA, Stephens PJ. Nature Medicine. 2012 Feb 12.
  9. Broad, hybrid capture-based next-generation sequencing identifies actionable genomic alterations in lung adenocarcinomas otherwise negative for such alterations by other genomic testing approaches Alexander Drilon1, Lu Wang1, Maria E. Arcila1, Sohail Balasubramanian2, Joel R. Greenbowe2, Jeffrey S. Ross2, Phil Stephens2, Doron Lipson2, Vincent A. Miller2, Mark G. Kris1, Marc Ladanyi1, Naiyer A. Rizvi1, 1Memorial Sloan Kettering Cancer Center, New York, NY, 2Foundation Medicine, Inc., Cambridge, MA Clin Cancer Res. 2015 Jan 7. pii: clincanres. 2683. 2014. [Epub ahead of print]

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We have a dedicated team of medical affairs and client services professionals to assist you at every step of the process from ordering FoundationOne to answering any questions you may have about the results delivered. We are interested in hearing your case reports of patients whose management and outcomes were altered as a result of a FoundationOne test.