Simultaneous chemo and immunotherapy may be better for some with metastatic bladder cancer

April 11, 2018

(New York, NY- April 11, 2018) --Researchers from Mount Sinai and Sema4, a health information company and Mount Sinai venture, have discovered that giving metastatic bladder cancer patients simultaneous chemotherapy and immunotherapy is safe and that patients whose tumors have certain genetic mutations may respond particularly well to this combination approach, according to the results of a clinical trial published in European Urology.

Though chemotherapy and immunotherapy have become standard options for the treatment of metastatic bladder cancer, it was previously unknown whether these therapies could be given together and whether chemotherapy's side effect of weakening the immune system would inhibit immunotherapy. The phase 2 trial was conducted at six cancer centers, and patients in the trial did not show any additional or more severe side effects than patients given chemotherapy or immunotherapy alone, a finding that showed the combination therapy is a safe alternative.

Researchers also generated evidence showing that immunotherapy could boost immune cells in the blood of patients receiving concurrent chemotherapy, allaying previous concerns that chemotherapy might counteract the effects of immunotherapy.

"Because chemotherapy and immunotherapy are the two pillars of treatment for metastatic bladder cancer, we sought to better understand how these treatments might be best given together," said Matthew Galsky, MD, Director of Genitourinary Medical Oncology and Professor of Urology, Medicine, Hematology and Medical Oncology at The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, and Principal Investigator of the study. "Already the results of this trial have inspired the creation of two more trials that seek to better the treatment of bladder cancer patients by combining chemotherapy with immunotherapy."

One of the new trials, which Dr. Galsky is heading at Mount Sinai and other centers, gives chemotherapy and immunotherapy to a subset of patients with earlier-stage bladder cancer to determine if this combination can head off the need for surgery to remove the bladder, a standard treatment but one with quality-of-life-altering implications that include wearing a urostomy bag outside the body to collect urine. The other trial combines two different chemotherapy regimens with immunotherapy to determine the best types of chemotherapy drugs to combine with immunotherapy.

Dr. Galsky said that the current trial epitomizes the importance of team science. Dr. Galsky, as well as Andrew Uzilov, PhD, Director of Cancer Genomics for Sema4, and Huan Wang, PhD, Sema4 bioinformatics scientist, and other researchers hypothesized that patients with tumors with particular genetic mutations might respond best to the combination of chemotherapy and immunotherapy. And indeed, they found that certain types of mutations in DNA damage response (DDR) genes were associated with better response to the combined chemotherapy and immunotherapy. If validated in subsequent studies, these findings could add a novel biomarker to the "precision oncology toolbox" and refine the selection of patients who might benefit from concurrent administration of chemotherapy and immunotherapy.

"Our work is an example of using genomics to enable precision medicine. By looking for loss-of-function mutations in DDR genes, we may be able to predict who will do well on a combined chemotherapy plus immunotherapy regimen," explained Dr. Uzilov. "In our study, we looked at a pool of 55 DDR genes as predictive biomarkers. We are now exploring further which of these genes, and what types of mutations within them, best predict treatment response, as well as the interplay of DDR status with other predictors of immunotherapy response."
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This study was supported by Bristol-Myers Squibb, Cancer Research Institute Clinical Strategy Team Grant, and National Cancer Institute (NCI) grant P30 CA196521.

About the Mount Sinai Health System

The Mount Sinai Health System is New York City's largest integrated delivery system encompassing seven hospital campuses, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. Mount Sinai's vision is to produce the safest care, the highest quality, the highest satisfaction, the best access and the best value of any health system in the nation. The System includes approximately 7,100 primary and specialty care physicians; 10 joint-venture ambulatory surgery centers; more than 140 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. Physicians are affiliated with the renowned Icahn School of Medicine at Mount Sinai, which is ranked among the highest in the nation in National Institutes of Health funding per investigator. The Mount Sinai Hospital is ranked No. 18 on U.S. News & World Report's "Honor Roll" of top U.S. hospitals; it is one of the nation's top 20 hospitals in Cardiology/Heart Surgery, Diabetes/Endocrinology, Gastroenterology/GI Surgery, Geriatrics, Nephrology, and Neurology/Neurosurgery, and in the top 50 in four other specialties in the 2017-2018 "Best Hospitals" issue. Mount Sinai's Kravis Children's Hospital also is ranked in six out of ten pediatric specialties by U.S. News & World Report. The New York Eye and Ear Infirmary of Mount Sinai is ranked 12th nationally for Ophthalmology and 50th for Ear, Nose, and Throat, while Mount Sinai Beth Israel, Mount Sinai St. Luke's and Mount Sinai West are ranked regionally. For more information, visit http://www.mountsinai.org/, or find Mount Sinai on Facebook, Twitter and YouTube.

About Sema4

Sema4 is a health information company founded on the idea that more data, deeper analysis, and increased engagement will improve the diagnosis, treatment, and prevention of disease. A Mount Sinai Health System venture based in Stamford, Conn., Sema4 is enabling physicians and consumers to more seamlessly engage the digital universe of health data, from genome test results and clinical records to wearable sensor metrics and more. The company currently offers advanced genome-based diagnostics for reproductive health and is building predictive models of complex disease. Sema4 believes that patients should be treated as partners, and that data should be shared for the benefit of all.

For more information, please visit sema4genomics.com and connect with Sema4 on Facebook, Twitter and YouTube.

The Mount Sinai Hospital / Mount Sinai School of Medicine

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