Building on a rich history of innovation, the genome scientists, bioinformaticians, and molecular pathologists at Memorial Sloan Kettering Cancer Center (MSK) developed MSK-IMPACT® (which stands for Integrated Mutation Profiling of Actionable Cancer Targets). The targeted tumor-sequencing test can detect more than 468 gene mutations and other critical genetic changes in common and rare cancers. It can also detect microsatellite instability, so we can identify people who may benefit from immunotherapy.
MSK-IMPACT® is the first laboratory-developed tumor-profiling test to receive authorization from the U.S. Food and Drug Administration. The test results give MSK physicians the ability to match people who have any solid tumor, regardless of origin, with a targeted agent based on the individual tumor’s molecular profile. The data helps guide treatment choices and can identify people who are candidates for clinical trials testing targeted therapies.
In a study published in Nature Medicine in 2017, MSK researchers found that nearly 37% of the first 10,366 people who had their tumors sequenced with MSK-IMPACT® had at least one actionable mutation. Today, more than 16,000 people have had their tumors sequenced with MSK-IMPACT®.
Using MSK-IMPACT®, we are able to conduct basket studies. These trials test therapies in people with tumors that have tested positive for specific mutations, regardless of cancer type or origin. Basket studies can include many more participants than disease-specific trials, allowing for faster enrollment and faster analysis of results. With MSK-IMPACT® as the universal screening program at MSK, we do not need to rely on slower, tissue-intensive, single-gene-screening assays run at a central reference laboratory to identify rare genomic subpopulations within particular cancer types.
The gene-sequencing test uses a hybridization capture method, enabling the detection and quantitative assessment of copy number alterations and selected structural arrangements. The tool detects the structural rearrangements by including baits for select intronic regions — a technique called intron tiling — for commonly rearranged genes and sequencing across the fusion points. The customized hybrid capture panel allows control over the content of the assay and provides room for growth as new targets are discovered by The Cancer Genome Atlas and the International Cancer Genome Consortium.
To definitively distinguish somatic mutations from inherited germline variants, we profile each tumor with blood as a matched normal control.
We developed a protocol-patient matching system to effectively and efficiently identify people to participate in precision medicine trials.
After obtaining a waiver from the Institutional Review Board, the principal investigator (PI) of a precision medicine study works with a data analyst to build a virtual cohort of patients that can be tracked during their care at MSK. The system can search molecular reports daily to provide a list of all current MSK patients who have a tumor with a specific genomic alteration. Search results can be refined to include diagnosis, stage, disease status, chemotherapy history, laboratory values, and upcoming appointments. PIs use a simple web interface to track eligible patients and can set automatic email alerts to notify care teams when specified events occur, such as a scan showing progression in a qualifying genomic alteration. This functionality has allowed us to accrue more participants for trials and has scaled up well as the number of precision medicine studies has increased. See Figure 1 for an overview of the protocol-matching system.