Reaching a Milestone: Researchers Report Results of First 10,000 Patients Analyzed by MSK-IMPACT

By Julie Grisham,

Monday, May 8, 2017

Test tube of blood with genetic code in the background
Summary

MSK researchers are reporting results from an analysis of the first 10,336 patients to undergo sequencing with MSK-IMPACT™ technology. More than 1,000 patients participated in clinical trials based on the sequencing results, and many more received other treatments based on the mutations found in their tumors.

By studying the genetic makeup of patients’ tumors, researchers and clinicians learn a tremendous amount about their disease, such as how different mutations affect responses to specific treatments. Now a team of nearly 100 Memorial Sloan Kettering researchers has reported the results of genomic sequencing for the first 10,336 patients to undergo analysis with the test called MSK-IMPACT.

In addition to enrolling in more-traditional clinical trials, patients who undergo genetic testing may also have the opportunity to participate in basket trials. These research studies evaluate drugs that target the mutations that drive tumors, regardless of where the cancer originated in the body. This approach allows for more-specific treatment selection and faster clinical trial enrollment and analysis.

“This study represents the culmination of a major collaborative effort in performing clinical sequencing of patients at MSK,” says geneticist Michael Berger, who is the senior author of the new study, published in Nature Medicine. “The first 10,000 patients were a big investment for us from a standpoint of both time and of money. This paper describes the landscape of clinically relevant mutations in people with advanced cancer and demonstrates how the tumor sequencing data contributed to their care.” In total, 10,945 tumors were sequenced as part of this study.

A Technology that Benefits Patients

The researchers reported in the study that nearly 37% of the patients who had their tumors sequenced through MSK-IMPACT had at least one actionable mutation. This means that drugs to target these mutations were available, either in a clinical trial or as part of the standard of care. Overall, 11% of patients, more than 1,000 in total, participated in clinical trials of treatments that directly targeted the genetic alterations in their tumors. (Some patients couldn’t participate because other health problems disqualified them.)

Today more than 16,000 patients have had their tumors sequenced with MSK-IMPACT.

But Dr. Berger points out that a much higher percentage actually benefited from the MSK-IMPACT testing. Many patients received treatment with targeted drugs that are already standard therapy; still others received immunotherapies. Research has shown that compared with people who have fewer mutations, those with a large number of mutations are more likely to respond to immunotherapy. In addition, sequencing may reveal that a person is unlikely to respond to a particular drug and thus spare them from unnecessary treatments and side effects.

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Expanding the Role of Genomic Sequencing

Until recently, genomic testing was considered routine practice only for patients with certain solid tumors, such as melanoma, lung cancer, and colon cancer. MSK-IMPACT is more inclusive and can be used on any solid tumor regardless of its origin, which could potentially offer better treatment options.

When it launched in 2014, the test looked for mutations in 341 genes known to play a role in cancer. That number has since expanded to 468.

This study represents the culmination of a major collaborative effort in performing clinical sequencing of patients at MSK.
Michael Berger
Michael Berger geneticist

The number of people sequenced is also growing. Although the paper reported on about 10,000 patients, that achievement was reached in summer 2016. Today, more than 16,000 patients have had their tumors sequenced with MSK-IMPACT. The figure is continuing to increase at a rate of 600 to 800 new patients each month. Sequencing efforts are currently focused on patients who have metastatic (stage IV) disease, because that is where the need for new treatments is greatest.

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Seeking Important Information in the Data

The focus on advanced tumors — including many from patients who have already received one or more treatments — has enabled MSK-IMPACT to produce valuable insights about disease progression and resistance. “We see a different spectrum of mutations than what has been observed in patients who are newly diagnosed with early-stage cancer,” explains Ahmet Zehir, Director of Clinical Bioinformatics and one of the study’s co-first authors. “We’ve found that certain genes are mutated more frequently in patients with advanced cancer who undergo MSK-IMPACT testing. This indicates that these genes are important for the progression of disease — how it spreads and how it develops resistance to therapy.”

Another difference is that all MSK patients who have their tumor sequenced by MSK-IMPACT also have noncancerous cells from their blood sequenced. “The most immediate benefit of this is that we can distinguish between tumor-specific mutations and those that are inherited in the germline, which don’t always have therapeutic significance,” says Ryma Benayed, technical director of clinical sequencing and the study’s other first author. By studying these normal blood samples, MSK researchers are gaining knowledge about the hereditary aspects of cancer, especially through work conducted by the Robert and Kate Niehaus Center for Inherited Cancer Genomics.

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 stripped out but their clinical records are included. This allows researchers at MSK and beyond to study the connections between particular genomic alterations and patients’ responses to therapy and eventual outcomes.

“Right now we’re exploring how we can expand this testing beyond people with metastatic disease,” Dr. Berger says. “If we can do this kind of analysis on biopsies taken before surgery, it could have implications for the treatment that patients receive both before and after surgery or determine whether surgery is even appropriate. We are only at the beginning of using this technology for the benefit of our patients.”

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Editor’s note: MSK-IMPACT was launched by the Molecular Diagnostics Service within MSK’s Department of Pathology. The service is led by Marc Ladanyi, who played a key role in developing the technology. Other groups that have played integral roles in developing and rolling out MSK-IMPACT include the Marie-Josée and Henry R. Kravis Center for Molecular Oncology (CMO), the Office of Clinical Research, Information Systems, and many clinical departments.

The study was supported by the MSK Cancer Center Support Grant (P30 CA008748), Cycle for Survival, the Farmer Family Foundation, and the CMO. This philanthropic support is especially important because many insurance companies consider genetic sequencing of tumors experimental and will not pay for it.

Comments

I have had two tumors taken out by Dr. Singer. i have one small tumor in my stomach. It is being monitored.

Are you able to take a specimen from my tumor that has been resected to analyze through the IMPACT technology.

thank you

arnold brustin

Dear Arnold, we recommend you talk with Dr. Singer about whether MSK-IMPACT testing is a good option for you and whether your tumor was preserved in a way that this testing could be done. Thank you for your comment, and best wishes to you.

I have had Genomic testing done at The Simon Cancer Center IU Hospital, and Foundations. My doctor is Dr. Loehrer. I have Thymoma which I had surgery and radiation treatments. It has spread to my lungs. I guess I am wondering if there is anything that my findings could help with your study or if there is anything you could do for me. I believe there were many mutations but they were able to identify one pathway.

I am presently being treated by Dr. Kris of MSK. I have stage 4 lung cancer that is ALK +. I have been taking Xalkori since October 2014.

Dear Dominick, thank you for sharing your story. Best wishes to you.

Diagnosed with cholangiocarcinoma exactly 26 months ago!
After different chemo treatments ,6 months ago I entered the AG-120 clinical trial and all I can say is that it works and I feel better than before my diagnosis and I have a super full life!!
I don't know if my trial is part of the MSK IMPACT but all I have to say to everyone in need: go for it!!
Thank you to the MSK research team! Thank you ! Thank you!

Dear Theonie, we're so glad to hear you're doing well. Thank you for your comment.

I was diagnosed w/ metastasized colon cancer which had spread to the liver in Jan. 2014. Thankfully, when my wife contacted MSK, I was referred to Dr.Nancy Kemeny who ordered a liver pump implanted. I received liver chemo until April 2016 and I've been receiving the systemic chemo every other week up to the present. Would MSK-IMPACT genome sequencing be considered for me? Could it be an alternative to the every-other-week systemic chemo that I'm presently receiving?

Dear Marshall, we recommend that you discuss this with Dr. Kemeny. If you had your surgery at MSK, there may be material available to do this testing. Otherwise, it may be possible to obtain a tumor sample to test. Thank you for your comment, and best wishes to you.

If you really wanted to make an impact and impressive discovery why would you not seek out people such as my sister who is on her deathbed with cancer having invaded her entire body from bone to lung.
Having undergone a Masectomy 37 years ago, having endured the poison chemotherapy, and having undergone a clinical trial medication that apparently did her no good. All I can say is why, why, why.?

Dear Phyllis, we are very sorry to hear about your sister. Thank you for your comment.

I have Pancreatic Neuroendocrine tumor (aka PNET). Would that type of cancer be a candidate for IMPACT study? I had a 2nd opinion from MSK's Dr. O'Reilly a few years ago - I find that neuroendocrine cancers are treated differently. Currently, I'm being treated by a former MSK doctor (Dr. Jhawer).

Dear Tim, MSK-IMPACT testing is generally offered to people with metastatic (stage 4) disease. If your cancer is advanced and you're interested in potentially participating in a clinical trial, you may want to consider having another consultation with Dr. O'Reilly or a different doctor at MSK. If you are interested, you can call Dr. O'Reilly's office or our main physician referral number at 800-525-2225. You can go to https://www.mskcc.org/experience/become-patient/appointment for more information on making an appointment. Thank you for your comment, and best wishes to you.

Dear MSK Representative,

I understand that my mother had several tumor samples taken during her initial laparoscopic surgery, and then later on when she received more extensive surgery after nine weeks of chemotherapy. She is currently NED, but her cancer has a high rate of recurrence. She had genetic testing, which revealed a mutation on her RAD50 gene. Is it possible to request genomic sequencing of her tumor samples, of course in consultation with her MSK surgeon who performed the procedure and the pathologist who provided the staging information in the first report? I'm sure they will let me know if she is a good candidate for the IMPACT study, but essentially what I'm wondering is if a referral from either the oncologist or pathologist is necessary? Thanks so much for your consideration in advance.

With sincerest gratitude,
Roland

Dear Roland, we recommend that your mother discuss this with her MSK surgeon. Generally, MSK-IMPACT is done for stage 4 (metastatic) tumors, but there may be some exceptions to this. Thank you for your comment, and best wishes to you and your mother.

Many thanks!

My husband, Don, 73 yrs. of age had colon cancer in 2005. After chemo for 6 months everything was going well. In January 2014 his doctor found his CRC had metastasized to his liver (2 tumors) and 1 in the peritoneal area. More chemo and liver surgery to remove them in July 2014. In July 2015 the tumors were back in same areas. More chemo and in 2016 he was put on capacitabine, which lowered his CEA levels for 6 months but now are rising. A CT test June 22, 2017 showed the same 3 tumors, now a new one in liver and one small one in lower left lung lobe. Would this MSK-IMPACT testing and the larotrectinib work for him?

Dear Carolyn, we're very sorry to hear about your husband's diagnosis. If MSK-IMPACT find that his tumor carries a TRK fusion, then it's possible that he could benefit from larotrectinib. It's also possible that tumor sequencing could reveal another mutation that might respond to a different targeted therapy. If you would like to learn more about arranging an appointment with one of our experts and getting his tumor analyzed, you can call 800-525-2225 or go to https://www.mskcc.org/experience/become-patient/appointment for more information on making an appointment. Thank you for your comment, and best wishes to you and your husband.

Does IMPACT include both somatic and germline testing? What is the timeframe for results from both of those testings -- are they done at the same time or sequentially?

My partner is currently a patient at MSK, for MDS &Multiple Myeloma. Are there new genetic therapies for such blood cancers. Thank you

Dear Irene, we have a number of therapies targeting genetic changes in clinical trials for these conditions. You may want to discuss the possibility of participating in a trial with your partner's healthcare team. Thank you for your comment, and best wishes to both of you.

I’m very fortunate to be a patient at MSK. I’m stage IV tnbc with mets to the liver. My liver biopsy slides began IMPACT testing on Nov 17th. What is the average time for results to be become available. Thank you for being part of an amazing team of healthcare providers❤️

Dear Linda, we are so glad to hear that you are happy with the care you're receiving here. We recommend you discuss the timing of your MSK-IMPACT results with your doctor or nurse. Thank you for your comment, and best wishes to you.

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