Immune-based therapy may help when melanoma spreads to brain

 A type of therapy that harnesses the immune system is giving new hope to people battling a once hopeless cancer — melanoma that’s spread to the brain.

New research involving more than 2,700 U.S. patients is confirming what specialists in the field have long known — that “checkpoint blockade” treatment can beat back these devastating tumors.

“Physicians who treat patients with melanoma brain metastases have seen first-hand the dramatic improvements in survival that immunotherapy can achieve,” said one such specialist, Dr. Jason Ellis.

“This study provides data to support our individual clinical observations,” said Ellis, a neurosurgeon at Lenox Hill Hospital in New York City. He wasn’t involved in the new study.

Checkpoint blockade agents are not chemotherapy — instead of acting directly on tumor cells, they manipulate the patient’s immune system so that it targets and destroys the melanoma cells.

This type of “immunotherapy” was approved by the U.S. Food and Drug Administration in 2011.

The new research was led by Dr. J. Bryan Iorgulescu, a postdoctoral fellow in pathology at Brigham and Women’s Hospital/Harvard Medical School in Boston. His team explained that about one in every 54 Americans will develop a melanoma skin cancer in their lifetime.

Luckily, most cases are detected early and easily cured via surgery. But sometimes the tumor has had time to spread, even to the brain. In fact, advanced melanomas are now the third-leading cause of metastatic brain cancer, the research team noted.

In its analysis, Iorgulescu’s group tracked outcomes from 2,753 patients with melanoma that had spread to the brain. The patients were treated at cancer centers nationwide between 2010 and 2015.

The study found that first-line treatment with checkpoint blockade immunotherapy was associated with a rise in median overall survival from 5.2 months to 12.4 months.

Treatment was also tied to an increase in the four-year overall survival rate: Just over 28 percent of patients who got the immunotherapy survived at least four years, compared to about 11 percent who didn’t get the therapy, the findings showed.

The researchers noted that survival benefits were even greater for those patients whose melanoma had not already spread beyond the brain, to organs such as the liver or lungs.

“Our findings build on the revolutionary success of checkpoint blockade immunotherapy clinical trials for advanced melanoma, and demonstrate that their substantial survival benefits also extend to melanoma patients with brain metastases,” Iorgulescu said in a Brigham and Women’s news release.

Dr. Michael Schulder helps direct neurosurgery at Long Island Jewish Medical Center in New Hyde Park, N.Y. He wasn’t involved in the new analysis, but agreed it confirms what many cancer specialists have long known, “namely, that the use of checkpoint inhibitors has revolutionized the treatment and outlook for patients with metastatic melanoma.”

The Boston researchers did offer one caveat, however: Not every patient has equal access to this expensive treatment. Insurance status was a real barrier to immunotherapy for some patients with these advanced tumors, and uninsured patients were much less likely to get the treatment compared to people with private insurance or those on Medicare.

The findings were published July 12 in Cancer Immunology Research.

More information

The U.S. National Cancer Institute has more on melanoma.

SOURCES: Jason Ellis, M.D., neurosurgeon, Lenox Hill Hospital, New York City; Michael Schulder, M.D., vice chair, neurosurgery, North Shore University Hospital, Manhasset, N.Y., and Long Island Jewish Medical Center, New Hyde Park, N.Y.; Brigham and Women’s Hospital, news release, July 12, 2018

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Half of Americans trying to lose weight

In a country where four out of 10 adults are obese, it’s probably good news that half of U.S. adults say they’ve recently tried to shed some pounds.

They did this most often through exercise, cutting calories and eating their fruits and veggies, according to a new government survey that tracked Americans’ weight-loss attempts between 2013 and 2016.

Overall, 49 percent of respondents said they’d tried to lose weight in the past year — including two-thirds of those who were obese.

As of 2016, almost 40 percent of American adults were obese, according to researchers with the U.S. Centers for Disease Control and Prevention’s National Center for Health Statistics (NCHS).

So it’s important to know how many Americans are trying to lose weight — and how they’re doing it, said Kirsten Herrick, a senior research fellow with the NCHS who worked on the study.

There were some positive signs, said a registered dietitian who wasn’t involved in the research.

The most common weight-loss methods were exercise and eating less — each reported by 63 percent of people aiming to shed pounds. And half said they were eating more fruits, vegetables and salads.

“The good news is that people seem to recognize that weight loss is about changing habits, not quick-fix diets,” said Connie Diekman, director of university nutrition at Washington University in St. Louis.

Sustainable diet changes are critical, Diekman said. That includes cutting sugary, fat-laden junk food, and replacing it with plenty of fruits, vegetables, fiber-rich grains and other healthful whole foods.

Regular exercise can improve your overall health, and may aid in weight loss, Diekman noted. But, she said, people need to make lasting changes in how they eat, rather than try fad diets.

The report was based on a nationally representative sample of Americans aged 20 and older. Many people said they’d tried to lose weight in the past year, though the figures varied among different groups.

Women were more likely than men to have aimed for weight loss (56 percent versus 42 percent), the findings showed.

Income made a difference as well, with wealthier men and women significantly more likely to say they tried to slim down.

It’s possible, Herrick said, that the disparity could reflect the barriers low-income Americans can face when it comes to losing weight — like having the time and place to exercise, or being able to afford healthy food.

But, she added, it’s impossible to know from this survey.

Besides turning to exercise and veggies, survey respondents also commonly said they’d cut down on junk food and fast food, and tried to limit sugar. Many said they “drank a lot of water.” The vast majority of people who tried to lose weight said they’d used at least two tactics.

What’s not clear is how often those efforts paid off.

Diekman pointed out that the “report provides a glimpse of what Americans are doing to achieve a healthy weight, but what it does not show is how individuals are doing.”

Since most Americans are overweight or obese, she added, doctors and other health providers should be asking people about how they view their weight and their health.

If you need help managing your weight, Diekman suggested talking to your doctor, who may refer you to a dietitian.

Having a plan that is “practical, achievable and maintainable” is key, she said.

The report was published July 12 in the CDC’s NCHS Data Brief.

More information

The U.S. National Heart, Lung, and Blood Institute has advice on achieving a healthy weight.

SOURCES: Kirsten Herrick, Ph.D., M.Sc., senior research fellow, National Center for Health Statistics (NCHS), U.S. Centers for Disease Control and Prevention; Connie Diekman, M.Ed., R.D., director, university nutrition, Washington University in St. Louis; July 12, 2018, NCHS Data Brief

https://bit.ly/2uojCUL

Probing the part of the brain where autism may begin

 The underpinnings of autism may lie in an unexpected part of the brain, a small study suggests.

Scientists conducted brain scans on 20 boys with autism and 18 boys without the neurodevelopmental disorder. The scans showed that boys with autism had a significantly flatter surface on the right side of their cerebellum. That side happens to be involved in language processing.

The researchers also found that a flatter cerebellum was associated with differences in thinking abilities and communication, two skills often affected by autism.

But the study did not prove that differences in the cerebellum caused autism.

Still, “Our findings suggest we may need to rethink the role of cerebellar function and structure in young individuals at risk for atypical brain development,” said senior study author Kristina Denisova. She’s an assistant professor of clinical neurobiology at Columbia University in New York City.

While the cerebellum is only 10 percent of the brain’s total volume, it contains 80 percent of all neurons (brain cells), the researchers explained. It had been believed that this area governed motor function for the most part, but recent research has hinted that it might also regulate implicit learning, sensory development and thinking skills.

Yet, most brain scan studies on autism have focused on the cerebrum, which is larger than the cerebellum despite having fewer neurons, the researchers said.

“That’s partly a function of the unique, irregular shape of the cerebellum, which is difficult to analyze with conventional imaging techniques,” Denisova explained in a Columbia news release.

“Imagine looking at only 20 percent of the brain’s neurons and attempting to paint a comprehensive picture of atypical development in humans based on such limited knowledge,” she said.

Denisova added that “one interpretation of the findings is that increased structural complexity of the cerebellum may enhance implicit learning in atypically developing boys.”

That question is now being investigated by the researchers in infants and toddlers who are at risk for developing autism later in life, the researchers said.

The findings were published online July 11 in the journal PLOS One.

More information

The Autism Society has more on autism.

SOURCE: Columbia University Irving Medical Center, news release, July 11, 2018

https://bit.ly/2zvjCXT

Abbott Gets FDA OK for Next-Gen Device to Treat Leaky Heart Valves

Abbott  (NYSE: ABT) today announced it received approval from the U.S. Food and Drug Administration (FDA) for a next-generation version of its leading MitraClip®heart valve repair device used to repair a leaky mitral valve without open-heart surgery. The transcatheter clip-based therapy, now on a third generation of product innovations, has been used to treat more than 65,000 patients worldwide over the last ten years. The next-generation MitraClip system provides cardiologists with advanced steering, navigation, and positioning capabilities for the clip, making it easier to use in difficult anatomies. The enhanced system is designed to allow for more precise placement during deployment, resulting in more predictable procedures, and additionally offers a second clip size with longer arms that expands the reach of the clip-based device.The additional clip size is designed to help doctors treat patients who have morecomplex anatomies when repairing the mitral valve. Abbott received CE Mark for the next-generation device earlier this year, allowing for sale of the devices in the European Union and other countries that recognize this regulatory designation. “Physicians rely on MitraClip as an alternative to surgery for patients who aren’t surgical candidates and may need treatment to relieve their symptoms or to survive,” said Francesco Maisano, M.D., Prof., UniversitätsSpital Zürich, Switzerland, who was an early implanter of MitraClip. “The enhanced MitraClip design allows for even more precise navigation, accuracy, and stability during valve repairs, which may be important when treating people with more complex or advanced valve disease.” A leaking mitral valve, known as mitral regurgitation (MR) is a serious, progressive heart disease in which the flaps of the mitral valve do not close properly, allowing blood to flow backward into the heart. Incidence of mitral regurgitation increases with age, with nearly one in 10 people over the age of 75 having moderate to severe disease1. Before MitraClip, people who were not eligible for the standard-of-care surgery to treat their MR could only manage their symptoms with medications that don’t stop the progression of the disease. Left untreated, MR leads to a variety of life-altering symptoms and severe complications, and may ultimately lead to heart failure and death.1,2,3. “Abbott engineers designed these enhancements based on feedback from doctors to improve device delivery and to treat more types of cases and anatomies,” said Michael Dale, vice president for Abbott’s structural heart business. “We’re committed to helping people with mitral regurgitation return to living their best lives, and these advances will enable doctors to treat even more patients without surgery.” MitraClip treats people with degenerative mitral regurgitation and is a therapy that is delivered via a catheter to the heart through a blood vessel in the leg. MR patients are often not eligible for the standard-of-care surgery because of advanced age, frailty, multiple comorbidities or other complicating factors and the therapy offers a minimally invasive alternative. Treatment with MitraClip provides almost immediate symptom relief and patients are released from the hospital on average after two days. Abbott recently began enrollment in the MitraClip EXPAND clinical study, a prospective study evaluating the safety and performance of the new MitraClip system in a contemporary real-world setting. Saibal Kar, M.D., director of Interventional Cardiac Research at the Smidt Heart Institute at Cedars-Sinai in Los Angeles, Calif., treated the first patient enrolled, and is the lead investigator of the study. EXPAND will enroll approximately 1,000 patients in more than 50 centers across the U.S. and Europe and interim results from the study are expected later this year. https://bit.ly/2mdePRd

Verma: Changes Coming to Stark Self-Referral Law

The Centers for Medicare & Medicaid Services (CMS) is hoping to issue a proposed regulation by the end of the year that would loosen the “Stark law” prohibiting physician self-referral, CMS administrator Seema Verma said Monday.

“One of the barriers around [promoting] value-based care is burdensome regulations, and that’s where Stark comes into it,” Verma said at a briefing sponsored by the Alliance for Health Policy and APCO Worldwide, a public relations firm here. “We are going to do something on Stark — I’m very certain about that — and we hope to have something out by the end of the year.”

The 1989 law, named for former congressman Fortney H. “Pete” Stark (D-Calif.), “prohibits a physician from making referrals for certain designated health services payable by Medicare to an entity with which he or she (or an immediate family member) has a financial relationship (ownership, investment, or compensation), unless an exception applies,” CMS notes on its website.

Designated health services include clinical lab services, physical therapy, occupational therapy, radiology, durable medical equipment, home health services, outpatient prescription drugs, and inpatient and outpatient hospital services.

During a panel discussion following Verma’s remarks, Richard Deem, senior vice president for advocacy at the American Medical Association (AMA), pointed out that the Stark law “was created in a whole different environment than we’re trying to operate in now … Right now we’re talking about more collaboration, whether it’s an ACO [accountable care organization] or a bundled payment arrangement. Obviously we’re going to have to rethink things if we want to collaborate and coordinate.”

Verma also discussed other moves that CMS was making to lessen the regulation burden on providers. The agency had previously announced that it was doing away with some of the current quality measures for home healthcare and dialysis providers.

“We did a nationwide listening tour, and talked to providers from different settings across the system, and we heard about the burden of the reporting,” Verma told MedPage Today. “We went back and took a look at all of the measures.”

When they did so, they found that many quality measures were “topped out” — 97% or 98% of providers had a positive score on the measure — “so why are we continuing to report [on it]?” she said. “The other thing we saw is that a lot of the measures were duplicative; providers were having to report the same thing across three or four programs, so we’re trying to eliminate that.”

In addition, “we need to think about the burden it’s creating on the healthcare system,” Verma continued. Providers “are spending so much time and energy reporting, when what we need providers to do is focus on patients. I was visiting a hospital in Ohio and they talked about having 14 or 15 people essentially in the basement working on quality measures and manually having to extract data from patient records. We need people on the front lines, not in the back room behind a computer screen.”

Eventually, “we want to get to a system where we can extract information from medical records, from claims data. That’s the overall direction we’re going in on quality measurement,” she said.

There is a tension between having too many quality measures and having enough relevant measures, said the AMA’s Deem. “We want to get out of checking the boxes, but if they parse down the measures too much, it may leave some physicians without a measure they can properly use.”

As for using claims data to do quality measurement, “the problem with claims data is that it doesn’t include a lot of the clinical data that you need to make the proper quality judgments,” he added.

Verma also hinted that the agency might be moving toward “site-neutral” payments, in which all Medicare providers are paid the same for a particular procedure or service no matter where it was preformed. As it stands now, “we’re paying differently for the exact same service in one setting versus another, and the provider community is responding to that,” she said. “You see hospitals buying up physician practices because then they can bill more for the exact same service.”

The idea of site-neutral payments did not sit well with Joanna Hiatt Kim, vice president for payment policy at the American Hospital Association. “The cost of care delivered in hospitals and health systems reflects the unique social goods that only they provide,” she said.

That would include “providing for standby capacity should a rare traumatic event occur, staffing and keeping the ED open 24/7, so if your child gets sick in the middle of the night or if you’re a victim of a hurricane or an earthquake or a wildfire, you can come in and a hospital is ready to care for you … we would [oppose site-neutral payment].”

Verma also responded to a question about a recent court ruling that invalidated Kentucky’s Medicaid waiver, which would have imposed work requirements — also known as “community engagement” requirements — on able-bodied Medicaid recipients. “This administration is committed to giving states flexibility, to giving people living in poverty a pathway out of that situation,” said Verma, who noted that she had recused herself from the Kentucky case and couldn’t talk about it specifically.

“States are trying to do innovative things … and we want to be supportive of that. This hasn’t changed our commitment to helping people rise out of poverty.”

https://bit.ly/2NIhkrk

Gilead gets Euro OK for HIV combo

Gilead Sciences, Inc. (NASDAQ: GILD) announced that the European Commission has granted Marketing Authorization for Biktarvy® (bictegravir 50mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg; BIC/FTC/TAF), a once-daily single tablet regimen (STR) for the treatment of HIV-1 infection. BIC/FTC/TAF combines the potency of the novel integrase strand transfer inhibitor (INSTI) bictegravir, with the demonstrated safety and efficacy profile of Descovy® (emtricitabine 200 mg/tenofovir alafenamide 25 mg; FTC/TAF), a guidelines-recommended dual nucleoside reverse transcriptase inhibitor (NRTI) backbone. Today’s decision makes BIC/FTC/TAF Gilead’s third FTC/TAF-based STR approved in the European Union in the past three years (see also Gilead Sciences Inc.).

In Europe, BIC/FTC/TAF is indicated as a complete regimen for the treatment of HIV-1 infection in adults without present or past evidence of viral resistance to the integrase class, emtricitabine or tenofovir. No dosage adjustment of BIC/FTC/TAF is required in patients with estimated creatinine clearance (CrCL) greater than or equal to 30 mL per minute. BIC/FTC/TAF has convenient dosing, does not require testing for HLA-B 5701, and has no food intake or baseline viral load or CD4 count restrictions.

“To help support the long-term health of people living with HIV, it is crucial to have regimens that deliver durable viral suppression with a high barrier to resistance,” said Professor Alan Winston, Professor of HIV and Genitourinary Medicine at Imperial College and Consultant Physician at St. Mary’s Hospital, London, UK. “In clinical trials through 48 weeks, BIC/FTC/TAF has shown high efficacy and zero resistance. With convenient dosing and few pre-screening or ongoing monitoring requirements, it has the potential to simplify treatment initiation, and follow-up over time.”

Today’s decision is supported by data from four ongoing Phase 3 studies: Studies 1489 and 1490 in treatment-naive HIV-1 infected adults, and Studies 1844 and 1878 in virologically suppressed adults. The trials are comprised of a population of 2,415 participants. BIC/FTC/TAF met its primary objective at 48 weeks in all four studies.

Through 48 weeks, no participants in any of the four studies failed BIC/FTC/TAF with treatment-emergent virologic resistance, no participants discontinued BIC/FTC/TAF due to renal adverse events and there were no cases of proximal renal tubulopathy or Fanconi syndrome. The most common adverse reactions in patients taking BIC/FTC/TAF were diarrhea, nausea and headache.

“We are pleased to offer BIC/FTC/TAF, the latest innovation in our comprehensive HIV research and development program, which encompasses prevention, treatment and cure,” said Andrew Cheng, MD, PhD, Chief Medical Officer, Gilead Sciences. “The approval of BIC/FTC/TAF demonstrates our continued commitment to improving care for people living with HIV, and we look forward to working with health authorities across Europe to ensure that BIC/FTC/TAF is made widely available as soon as possible.”

Additional studies not included in the marketing authorization application are also ongoing, including dedicated studies in women, and in adolescents and children.

BIC/FTC/TAF was approved by the U.S. Food and Drug Administration (FDA) on February 7, 2018.

https://bit.ly/2uh5NqP

Xencor doses 1st patients for Phase 1 cancer antibody study

Xencor, Inc. (NASDAQ: XNCR), a clinical-stage biopharmaceutical company developing engineered monoclonal antibodies for the treatment of autoimmune diseases, asthma and allergic diseases and cancer, today announced that the first patient has been dosed in XmAb20717-01 (DUET-2), a Phase 1, first-in-human, clinical trial of XmAb®20717, a bispecific antibody that simultaneously targets PD-1 and CTLA-4 immune checkpoints for the treatment of multiple advanced solid tumors.

“Built on the scaffold of Xencor’s XmAb® bispecific Fc domain, XmAb20717 is the most advanced candidate in our suite of tumor microenvironment activators,” said Paul Foster, M.D., chief medical officer at Xencor. “The dual blockade of PD-1 and CTLA-4 with XmAb20717 may promote superior T cell activation and proliferation compared to anti-PD-1 alone, and we look forward to studying its safety, tolerability and therapeutic activity in clinical trials.”

By the end of 2018, Xencor expects to file Investigational New Drug applications for two additional tumor microenvironment activators including XmAb®23104, a PD-1 x ICOS bispecific antibody, as well as XmAb®22841, a CTLA-4 x LAG-3 dual checkpoint inhibitor.

DUET-2 is a Phase 1 multiple-dose, dose-escalation study that will characterize the safety and tolerability, pharmacokinetics, pharmacodynamics, immunogenicity and preliminary anti-tumor activity of intravenous administration of XmAb20717 in patients with selected advanced solid tumors. For more information about DUET-2 please visit to https://clinicaltrials.gov (identifier: NCT03517488).

As opposed to traditional monoclonal antibodies that target and bind to a single antigen, bispecific antibodies are designed to elicit biological effects that require simultaneous binding to two different antigen targets. Xencor’s XmAb bispecific Fc domain technology is designed to maintain full-length antibody properties in a bispecific antibody, potentially enabling favorable in vivo half-life and simplified manufacturing.

https://bit.ly/2mbZ0ub