Barbara Gitlitz, M.D.
This study lays the groundwork for discovery of novel targetable genotypes as well as heritable and environmental risk factors for lung cancer patients under 40. We'll be evaluating 100 or more patients in this initial study and hope to apply our findings to a larger follow-up study in the future.
Geoffrey Oxnard, M.D.
I was first diagnosed with lung cancer in 2003. After months of chemotherapy and surgery I was considered in remission. I became outraged at the lack of support financially and the lack of awareness. After my diagnosis my mother was diagnosed with lung cancer and unfortunately, after she passed away we realized that her father had in fact passed away from lung cancer as well.
My commitment to this fight is not only personal but a commitment to everyone who has been diagnosed and faces the same thing I did. My daughters have been by my side since day one and have committed to this fight as well. I couldn't be more proud to fight this ugly disease and be by their side at the same time.
It’s heartbreaking when you meet young adults with lung cancer, who should have their full lives ahead of them but instead are fighting for their lives because of the lack of lung cancer treatments. This groundbreaking study will investigate why young adults under the age of 40 are getting lung cancer and whether they have a unique cancer subtype, or genotype, that can be treated differently.
Focused study of lung cancer in young adults will provide new insight into lung cancer biology, facilitating the identification of a new genome-defined subtype of lung cancer requiring a unique clinical management strategy.
- To perform comprehensive genomic analysis of young lung cancer patient samples to facilitate delivery of targeted therapies and clinical trial enrollment
- To characterize the impact of young age at lung cancer diagnosis on the genomic landscape of primary lung cancer
- To establish a prospective registry of young lung cancer tissue specimens for investigational tumor and germline genomics
- To study next-generation sequencing (NGS) of cell-free plasma DNA and its ability to predict for a targetable genotype in patients with young lung cancer
In breast cancer and leukemia, research has demonstrated that diagnosis at a younger age is associated with a distinct biology and natural history; however, lung cancer biology in the young (under 40) has never been systematically studied. Technological advances, such as next-generation sequencing, now provide tools to study lung cancer genetics in younger patients who typically do not express common mutations. The investigators will use this sequencing to determine whether young lung cancers harbor a distinctive spectrum of genetic mutations requiring individualized management. Studying this biologically unique population may also identify new genetic sub-types needing targeted treatment strategies. This exciting study leverages ALCMI’s network of cancer centers/research management systems and ALCF’s patient outreach.
The Addario Lung Cancer Medical Institute (ALCMI), a patient-founded/-focused non-profit research consortium, is directly facilitating the study. This study is capturing pilot data to help us determine whether lung cancer in Adolescent and Young Adult (AYA) patients harbors a unique spectrum of genetic mutations that can be targeted with currently available therapeutics. Under the leadership of Barbara Gitlitz, MD (U. of Southern California, a member of ALCMI's consortium) is the first multi-center, US/European collaborative study to prospectively analyze the genomes of AYAcancer patients, and will help us understand how lung cancer occurs in young people as well as associated potential inheritable and environmental risk factors. Clinical genomics (FoundationOne and/or FoundationOne Heme panels) will be performed at no charge for qualifying participants by Foundation Medicine Inc.
Critically, patients may participate via the ALCMI study website (https://www.openmednet.org/site/alcmi-goyl), so there is no need for travel. This is a compelling example of bringing research to the benefit of patients where they live.
This research study includes collaborating institutions in the United States and Europe: University of Southern California, Los Angeles, CA (Barbara Gitlitz, MD), Dana-Farber Cancer Institute, Boston, MA (Geoffrey Oxnard, MD), University of Torino, Turin, Italy (Giorgio Scagliotti, MD, PhD & Silvia Novello, MD, PhD), and soon others.
Why is this important?
We hope this study will lay the groundwork for discovery of novel targetable genotypes as well as heritable and environmental lung cancer risk factors. Performing comprehensive genomics on lung cancer tumors from patients diagnosed at age 40 or younger represents a new and untapped strategy for identification of new targetable genotypes. Discovery of these genotypes is the first step in developing specific drugs to target and inhibit these mutations that drive the cancer. Our results may be an impetus for other groups to further explore other specific populations of lung cancer until it is no longer a disease with a “cookie cutter” approach to treatments and rather one where a personalized approach leads to significantly improved outcomes.
Lung cancer is the second most common cancer in both men and women (not counting skin cancer). In men, prostate cancer is more common, while in women breast cancer is more common. Annually, lung cancer accounts for about 14% of all new cancers, but accounts for 27% of cancer deaths in the United States.
Primary lung cancer is increasingly understood as a heterogeneous disease made up of genomically defined subtypes requiring distinct treatment strategies. We hypothesize young age at diagnosis ( < 40 years) is a clinical characteristic associated with an increased chance for a targetable genomic alteration. This study will prospectively characterize the somatic (acquired) and germline (inherited) genomics of young lung cancer. Our goals are to identify a genomically enriched subtype of lung cancer, facilitate delivery of targeted therapy and lay groundwork for further studies of heritable and environmental lung cancer risk factors.
Who will benefit?
As devastating as a diagnosis of lung cancer is, it is even more dreadful when it afflicts young adults in the prime of their lives. Interestingly, it has been found that ALK and ROS1 rearrangements, which are associated with sensitivity to treatment with crizotinib, are both relatively more common in younger lung cancer patients. While young age is well established as a marker of a distinct biology in cancers such as acute leukemia and breast cancer, the biology of lung cancers occurring at a young age has not been studied. Technologic advances such as comprehensive Next-Generation Sequencing (NGS) now give us the tools to efficiently study the genomic alterations of lung cancer in young adults.
Facts and Figures:
- About 228,190 new cases of lung cancer will be diagnosed (118,080 in men and 110,110 in women).
- There will be an estimated 159,480 deaths from lung cancer (87,260 in men and 72,220 among women), accounting for about 27% of all cancer deaths.
- Lung cancer is by far the leading cause of cancer death among both men and women. Each year, more people die of lung cancer than of colon, breast, and prostate cancers combined.
- Lung cancer mainly occurs in older individuals; the average age at the time of diagnosis is about 71 years.
- About 2 out of 3 people diagnosed with lung cancer are 65 or older; fewer than 2% of all cases are found in people younger than 45. The probability of developing an invasive lung cancer prior to age 39 is 0.03%.
Approximately 80% of lung cancers are non-small cell lung cancer (NSCLC) while the remaining 20% are classified as small cell lung cancer (SCLC). If NSCLC is detected before spreading to distant sites or invading important local anatomy then surgery is the best treatment with a five-year survival (depending on stage) of 40 to 90%. Adjuvant chemotherapy appears to add modestly to this survival, but optimum selection of patients for therapy and appropriate agents is very unclear, and only about one quarter of NSCLC is diagnosed at surgically resectable stages. The majority of lung cancer is diagnosed at an advanced, incurable stage. The 5-year lung cancer survival rate for all stages combined remains a dismal 15%.
Non-small cell lung cancer is increasingly understood as a genomically diverse disease made up of multiple largely non-overlapping genotype-defined subtypes requiring different treatment strategies. State-of-the-art management of lung cancer now depends upon assays for identifying targetable genotypes (e.g. EGFR mutations, ALK rearrangements) as well as clinical strategies for identifying patients benefitting most from genotyping (e.g. adenocarcinoma histology, never-smokers). This landscape has become increasingly complicated with the identification of a variety of low prevalence genotypes (1-2% of NSCLC) that may be highly targetable but difficult to test for (such as BRAF mutations, HER2 insertions, ROS1 and RET rearrangements, MET amplifications, and potentially many more yet to be discovered.)
Clinical Genomics Testing:
A. Patients with metastatic non-squamous NSCLC who have tested negative for all of the following 7 genomic alterations* will undergo additional testing using the FoundationOne™ Heme test; seeking to uncover additional driver alterations that might guide targeted treatment options.
*Mutations: EGFR, KRAS, HER2, BRAF Rearrangements: ROS1, ALK, RET
B. Patients with metastatic non-squamous NSCLC who have tested negative for some of these 7 defined alterations* but had not been tested for all of them will undergo NGS using the FoundationOne™ test. If they are negative for these defined alterations then the FoundationOne™ Heme test will be performed.
C. Patients known to harbor one or more of the seven defined alterations but who have progressed on genotype-directed targeted therapy at time of enrollment will be eligible for repeat genomics of a biopsy taken following progression using the FoundationOne™ Heme test.
D. Patients diagnosed with SCLC or metastatic squamous NSCLC will undergo NGS of their tumor using the the FoundationOne™ test.