
Knowing more about the genetic changes that drive tumors helps to open the door for personalized medicine. Image credit: Tek Image / Science Source
The US Food and Drug Administration has announced the authorization of MSK-IMPACT™. The test was developed by Memorial Sloan Kettering’s Department of Pathology to look for genetic mutations and other alterations in patients’ tumors. Knowing more about the changes driving an individual tumor helps open the door for personalized medicine, in which a person is matched with a treatment that targets the specific weaknesses in his or her cancer.
MSK-IMPACT, which stands for integrated mutation profiling of actionable cancer targets, has been used to analyze the tumors of people with advanced cancer being treated at MSK since January 2014. It is based on a technology called high-throughput next-generation sequencing. This means the most critical parts of the cancer genome — the complete string of DNA “letters” in a cell — can be profiled very quickly and with great sensitivity. When the test was first developed, it looked for alterations in 341 cancer-associated genes. Today, it looks for alterations in 468 genes. These alterations may be seen in both common and rare cancers.
“The experts at the FDA recognized the quality of our test and chose to partner with us to help determine how these kinds of tests are evaluated,” says geneticist and pathologist Michael Berger, who led the development of the test. “MSK-IMPACT will set a precedent for future authorization of tests developed by both academic and commercial labs.”
The FDA’s authorization of MSK-IMPACT as well as some recent FDA drug approvals signal a new phase for precision medicine. It could potentially lead to broader insurance coverage for genomic-sequencing panels in oncology.
Building on a History of Innovative Cancer Care
MSK-IMPACT was already approved by the New York State Department of Health as a clinical test. It is now the first tumor-profiling laboratory-developed test to receive authorization through the FDA.
The MSK-IMPACT test is carried out by MSK’s Molecular Diagnostics Service, which is led by physician-scientist Marc Ladanyi. To date, more than 20,000 MSK patients with advanced cancers have had their tumors sequenced. The resulting data have helped guide therapy while also providing a wealth of new information that is driving new investigations in the laboratory.
“It was a tremendous effort to develop MSK-IMPACT, orchestrated by many people with diverse backgrounds,” says Ahmet Zehir, MSK’s Director of Clinical Bioinformatics.
Dr. Ladanyi adds, “Obtaining FDA authorization is yet another confirmation of the amazing team we have built and the considerable efforts we have invested in bringing this into routine patient care at MSK.”
Back to topUsing Sequencing Results to Guide Cancer Treatment
“Pathology guides almost every decision point in the cancer treatment process. MSK-IMPACT has enabled our pathologists to provide a better understanding of the genetic underpinnings of each patient’s illness,” says David Klimstra, Chair of MSK’s Department of Pathology. “The valuable data obtained through the sequencing can guide treatment choices and, in some cases, identify patients who are candidates for a cancer clinical trial.”
According to a study published earlier this year in Nature Medicine, which looked at the first 10,336 patients to have their tumors sequenced with MSK-IMPACT, nearly 37% had at least one actionable mutation. This means that drugs targeting these mutations were available. Based on those testing results, the paper reported, 11% of patients — about 1,000 people — were able to participate in clinical trials of treatments that directly targeted the genetic alterations in their tumors. The study included contributions from more than 100 MSK investigators and was led by Dr. Berger, who is also an Associate Director of the Marie-Josée and Henry R. Kravis Center for Molecular Oncology (CMO).
In addition to patients who got targeted therapies based on their testing results, others were found to exhibit mutational profiles suggesting they were more likely to respond to immunotherapy. One of these abnormalities, known as microsatellite instability (MSI), occurs due to a defect in a process called DNA mismatch repair. Tumors with MSI are characterized by hundreds or even thousands of mutations. One component of the FDA’s authorized intended use for MSK-IMPACT is MSI detection, which adds another facet to the significance of this test.
Earlier this year, the FDA approved the immunotherapy drug pembrolizumab (Keytruda®) for the treatment of tumors with MSI, regardless of where the tumors appear in the body. Luis Diaz, Head of the Division of Solid Tumor Oncology in MSK’s Department of Medicine, led the trials that resulted in that approval.
Back to topData Sharing for Greater Benefit
All of the data collected through MSK-IMPACT testing are being made available to the larger scientific community through a database developed at MSK called the cBioPortal. Patients’ identifying information is removed, but basic clinical data are included, allowing researchers to study the connections between particular genomic alterations and the patients’ responses to therapy and their eventual outcomes.
Data from MSK-IMPACT are also being shared through AACR Project GENIE, a collaboration among eight leading cancer centers that aims to take advantage of genomic sequencing of tumors to advance precision oncology. Project GENIE — which stands for Genomics Evidence Neoplasia Information Exchange — was created by the American Association for Cancer Research (AACR) and is being spearheaded by Charles Sawyers, Chair of MSK’s Human Oncology and Pathogenesis Program. MSK has contributed the largest number of patients to the project, thanks in part to philanthropic support from the CMO, which coordinates many of MSK’s molecular oncology efforts. The CMO also funds sequencing that patients’ insurance doesn’t cover.
Back to topComments
SONDRA F STALLARD
Nov 17, 2017 • 7:23 PM
Memorial Sloan Kettering
Nov 20, 2017 • 8:26 AM
In reply to With FDA approval, does this… by SONDRA F STALLARD
Dear Sondra, the MSK-IMPACT test is currently performed only on MSK patients, and specifically those who have cancer that has spread to other parts of the body (stage IV). There are other genetic tests that are done on earlier-stage lung tumors, and these are available at many hospitals, including MSK. These tests are performed on the tissue after it has been removed via biopsy. If you would like to come to MSK for a consultation, the number to call is 800-525-2225. You can go to https://www.mskcc.org/experience/become-patient/appointment for more information on making an appointment.
If you are not able to travel to New York, we recommend that you find doctors in your area who are affiliated with a National Cancer Institute-designated cancer center. You can find the list here:
https://www.cancer.gov/research/nci-role/cancer-centers
Thank you for your comment, and best wishes to you.
Eduardo Franco
Dec 21, 2017 • 3:17 PM
Memorial Sloan Kettering
Dec 22, 2017 • 1:32 PM
In reply to What is approximately the… by Eduardo Franco
Dear Eduardo, the MSK-IMPACT test is currently available only to Memorial Sloan Kettering patients. If you are interested in becoming a patient, you can contact out International Center at international@mskcc.org or go to https://www.mskcc.org/experience/become-patient/international-patients for more information. Thank you for your comment, and best wishes to you.
Raymond PINEIRO
Dec 21, 2017 • 5:49 PM
Memorial Sloan Kettering
Dec 22, 2017 • 1:30 PM
In reply to Will this help me with my… by Raymond PINEIRO
Dear Raymond, we are sorry to hear about your diagnosis. If the MSK-IMPACT test finds mutations in your cancer that can be targeted with drugs, it may lead to treatment recommendations. These could be approved drugs or those that are available through clinical trials. If you would like to make an appointment to learn more, you can call 800-525-2225 or go to https://www.mskcc.org/experience/become-patient/appointment for more information. Thank you for your comment, and best wishes to you.
REV
Dec 25, 2017 • 8:15 PM
Cecile Tousignant
Mar 21, 2018 • 8:04 PM
Memorial Sloan Kettering
Mar 22, 2018 • 6:10 PM
In reply to What is the out-of-pocket… by Cecile Tousignant
Dear Cecile, the MSK-IMPACT test is only available to MSK patients. If you are interested in becoming a patient you can contact our International Center at international@mskcc.org or go to https://www.mskcc.org/experience/become-patient/international-patients for more information. Thank you for your comment, and best wishes to you.
Laura Montebello
May 30, 2018 • 8:19 AM
I was dx with stage 3b NSCLC one year ago. I’ve done very well with traditional chemo and radiation and all that is left is a 2cm nodule. My doctor had me on imfinzi but it is not killing this last little cancer and it makes me sick. I stopped it. I would like a second opinion. Can a doctor contact me? I’m local in NYC. I want this gone.
Memorial Sloan Kettering
May 30, 2018 • 4:03 PM
In reply to I was dx with stage 3b NSCLC… by Laura Montebello
Dear Laura, we’re sorry to hear about your diagnosis. If you would like to come to MSK for a second opinion, you can call 800-525-2225 to schedule an appointment. You can go to https://www.mskcc.org/experience/become-patient/appointment for more information. Thank you for your comment, and best wishes to you.
Dotty Jordan
Jun 5, 2018 • 12:58 AM
AB
Jul 20, 2018 • 3:43 PM
Dear AB, we’re sorry to hear about your husband’s diagnosis. You can contact one of our insurance specialists at 646-497-9176 to discuss this.
If you have expenses that are not covered, you may be eligible for our Financial Assistance Program. You can learn more here: https://www.mskcc.org/insurance-assistance/assistance
Thank you for your comment, and best wishes to both of you.
Monica
Oct 4, 2018 • 3:07 PM
Dear Monica, we’re sorry to hear about your diagnosis. MSK-IMPACT is available only to MSK patients. If you are interested in arranging a consultation to learn more about this testing and find out if you may be eligible for a trial or another treatment based on the genetics of your tumor, you can call 800-525-2225 or go to https://www.mskcc.org/experience/become-patient/appointment for more information. Thank you for your comment and best wishes to you.
With FDA approval, does this mean that this technology and approach to evaluating tumors will be available to medical centers other than SK? I have a 2cm mass just discovered in my lung and have not yet had a biopsy or removal but it appears to be malignant. Trying to determine if I should come to SK or whether the test will be available in the Washington DC area where I live. Also does one have the test prior to or after tissue removal?