A Promising New Cancer Drug

Promising New Cancer Drugs Empower the Body’s Own Defense System

“If you look five years out, most of this meeting will be about immunotherapy,” said Dr. Mario Sznol.
SCOTT MORGAN / ASCO
By ANDREW POLLACK
June 3, 2013

CHICAGO — The early success of a new class of cancer drugs, revealed in test results released here over the last several days, has raised hope among the world’s top cancer specialists that they may be on the verge of an important milestone in the fight against the disease.

The excitement has spread to Wall Street. Shares of Merck and Bristol-Myers Squibb, which are developing such drugs, rose more than 3 percent on Monday after data from their studies was presented over the weekend at the meeting of the American Society of Clinical Oncology.

The drugs, still generally in early testing, work in an entirely new way, by unleashing the immune system to attack cancer cells much as it attacks bacteria. That could be an alternative to often-debilitating chemotherapy.

Finding ways to use the body’s own defenses has been a goal since the late 1800s, when a New York surgeon named William B. Coley noticed that cancer disappeared in a patient who had a severe bacterial infection.

He then began injecting bacteria into cancer patients to rev up their immune systems. His claims of success were disputed and most attempts since then to harness the immune system have not worked.

The new drugs work by disabling a brake on the immune system called the programmed death 1 receptor, or PD-1. And although the data presented at the meeting was from the earliest stage of testing only, the drugs were the center of attention here, with some doctors predicting that cancer treatment was about to shift.

“If you look five years out, most of this meeting will be about immunotherapy,” said Dr. Mario Sznol, a professor of medical oncology at Yale.

Analysts, who predict billions of dollars in sales, are trying to determine which of the three front-runners — Merck, Bristol-Myers and Roche — have the best drug and how soon the drugs could reach the market. Some think it could be as early as a year and a half from now.

“I think all of you recognize this is a very special moment in oncology,” Dr. Roger M. Perlmutter, head of research and development at Merck, told analysts Sunday at a standing-room-only meeting.

Harnessing the immune system is appealing for several reasons. It might be applicable to many different types of cancer. It might produce longer lasting remissions than can be achieved by chemotherapy or the newer targeted drugs. And it seems somehow more natural and holistic.

“It seems the right thing to do to stimulate our body’s defense rather than take some kind of poison,” said Therese Bocklage, a cancer patient and pathologist from Albuquerque.

Dr. Bocklage thought she had bruised her leg moving a Christmas tree in late 2011. It turned out to be the return of the melanoma she thought had been successfully eradicated by surgery 20 years earlier.

She has been taking Merck’s experimental PD-1 inhibitor, lambrolizumab, as part of a clinical trial since January 2012, and her tumors have disappeared. “If I had had this turn up not last year but six years ago, most likely I’d be dead,” she said.

But there are reasons to be cautious. This is cancer, after all. Many other hoped-for miracles have failed to materialize. This is a conference that has hailed drugs that extend lives by only a few weeks as breakthroughs.

“We’re so used to failure, we get excited very easily,” said Dr. Kim Margolin, an expert on melanoma and immune therapies at the Seattle Cancer Care Alliance.

Most of what is known about the PD-1 drugs is that they shrink tumors significantly in 15 to 50 percent of patients. It is still not clearly established, though there are some hints, that the drugs will let people live longer.

And results seen in trials, under idealized conditions, do not translate perfectly to the real world. One poster presented here looked at use in Britain of Yervoy, a melanoma drug approved in 2011 that disables a different immune system brake. Median survival has been only about half of what was seen in clinical trials.

Moreover, just because the immune system is involved does not make something safe. Ask anyone with lupus, multiple sclerosis or other diseases caused by an aberrant immune system.

Yervoy, made by Bristol-Myers, has some serious side effects caused by overstimulation of the immune system. The newer PD-1 drugs seem remarkably well tolerated so far, though lung inflammation is seen in some patients.

For the last decade or so, the emphasis in oncology has been so-called targeted therapy, in which drugs counteract particular genetic mutations that drive tumor growth. These were supposed to displace conventional chemotherapy, which tends to poison fast-growing cells, both cancerous and healthy ones, causing serious side effects.

Targeted therapy has had some great successes, particularly the leukemia drug Gleevec. But cancer cells, which tend to mutate rapidly, can develop resistance to the targeted therapies. And it is becoming more difficult to develop drugs for each narrow population of patients with a particular tumor mutation.

The PD-1 drugs are in a sense a return to a one-size-fits-all approach. And it might be harder for the tumor to become resistant to the immune system, which can adapt, than to a single drug.

In fact, what most excited researchers here this weekend was “the tail.” When researchers plot on a graph how many patients remain alive over time, the curves tend to drop to near zero for metastatic cancer. A successful drug slows the rate of decline, but eventually almost all patients die from the cancer.

But with Yervoy and, experts hope, with the PD-1 drugs, there appears to be fraction of patients who do not die of the disease, at least for a long time. The curve levels out in a plateau.

Dr. Sznol said that of five patients treated at Yale with the Bristol-Myers PD-1 blocker, nivolumab, two had no evidence of recurrence even two years after stopping the drug.

Over all, 133 melanoma patients at various clinics took nivolumab in the Phase 1 trial. Median survival was 16.8 months, with 62 percent of patients alive at one year and 43 percent alive after two years. There was no comparison group in the study, but with the existing melanoma drugs, about 24 to 33 percent of patients are alive after two years, Dr. Sznol said.

So if the immune system is so effective, why doesn’t it cure cancer on its own? One reason is that cancerous cells are the body’s own cells, though mutated, and might not be recognized by the immune system as foreign. Another is that the tumors act to suppress the immune system.

Much of the previous attempts at cancer immunotherapy have focused on the first problem — trying to train the immune system to recognize the tumor and attack it.

The PD-1 drugs tackle the second problem of immune system suppression. How many cancers this will work for is still unclear. Much of the early work has been in melanoma, which is known to be more susceptible than many other tumors to immune system attack. There are cases, though rare, in which the immune system vanquishes melanoma on its own.

What is encouraging doctors is that the drugs can shrink some lung cancer tumors, which have not been considered particularly susceptible to immune attack. There are sporadic reports of cases with other cancers as well, like colorectal cancer.

http://mobile.nytimes.com/2013/06/04/health/promising-new-cancer-drugs-empower-the-bodys-own-defense-system.html

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Betty Hayden is Back to Pruning Roses After Fighting Rare Brain Cancer

After Brain Cancer Battle, Orange County, CA, Resident Picks Up Active Life Where She Left Off

Released: 5/31/2013 8:00 PM EDT
Source Newsroom: Cedars-Sinai Medical Center

Newswise — LOS ANGELES (June 3, 2013) – Westminster resident Betty Hayden loves to work in her yard and looks forward to traveling on weekends to dog shows with her daughter. But the retired school employee’s active lifestyle came to a halt last June with the sudden appearance of aggressive brain tumors.

After the diagnosis, Hayden’s daughter, Tammy Porter, expected doctors to quickly create a coordinated treatment plan. When they didn’t, she contacted brain cancer specialists at Cedars-Sinai Medical Center, where Hayden was evaluated and hospitalized within days. A year later, the cancer is in remission and Hayden is back in action, tending to her yard a couple of hours a day.

“In my opinion, they saved my mom’s life because they worked so fast to get us in,” said Porter, who first noticed changes in Hayden’s behavior during a weekend dog show in Ventura.

“She was going to bed really early, which isn’t like her,” Porter said. ”My mom can run circles around everyone else, but she was going to bed at 7 o’clock and sleeping a lot. She just wasn’t 100 percent herself. She was walking a little to the left, and I noticed that when she was talking, she sometimes would throw in a word that was kind of out of left field,” said Porter, who looks out for her mom who lives alone after being widowed about 10 years ago. They made an appointment for Hayden to see her doctor as soon as they got home.

Hayden’s behavior at the brief doctor’s visit was normal and blood tests were negative. But, Porter, convinced something wasn’t right, asked if a brain scan could be done.

“After the CAT scan, I got a call from the doctor, saying, ‘Your mom has two masses in her brain. You need to get to an emergency department ASAP,” Porter said, adding that her mother, 72, has always been fit, healthy and active. A biopsy found that the masses in her brain were cancerous.

“That was just horrible. I got the call and sat down with her and told her. … It’s amazing how something you don’t even know about just all of a sudden changes your life,” Porter said.

Hayden said the doctor seemed indifferent: “I said, ‘Now what do we do?’ And the doctor said, ‘We’re finished. You have to go see another doctor.’”

But Porter, believing her mother needed medical attention sooner rather than later, grew frustrated with the doctors’ apparent lack of interest, urgency and follow-up. As she tried desperately to reach unavailable doctors, she asked a friend to search the Internet for other options. The name of Keith L. Black, MD, chair of the Department of Neurosurgery at Cedars-Sinai, came up, and Porter sent an email to James Villalobos, RN, program development coordinator, in the department.

“It was about 9 o’clock on a Saturday night and I emailed Dr. Black’s office, not expecting, of course, to hear from them until Monday. But that’s when James called back. He called me back that night, at 9 o’clock. I was amazed,” Porter recalled, adding that she was even more impressed when Villalobos arranged coordinated consultations at Cedars-Sinai a few days later.

She and her mother met with neurosurgeon Chirag Patil, MD, director of the Center for Neurosurgical Outcomes Research, and neuro-oncologist Jeremy Rudnick, MD, a brain cancer expert in the Department of Neurology and the Department of Neurosurgery. Because Hayden’s cancer was not amenable to surgery, Rudnick took the lead.

“He looked at her MRIs and started telling us about this disease,” Porter recalled. “He said, ‘I’d like to get you in right now. This is a fast-growing cancer.’ He showed us her MRI pictures. This was the first time we had seen them. Her brain center line was totally out of skew. Her brain had so much swelling because of the tumors it’s amazing she didn’t have more side effects.”

Rudnick said Hayden’s cancer, central nervous system lymphoma, a type of non-Hodgkin lymphoma, is so rare that a general hospital may see a case only once every five years; Cedars-Sinai doctors treat 10 or 20 patients a year. It’s considered a stage 4 lymphoma, one of the most aggressive forms of the disease.

“With this disease, we can see a doubling of tumor in just weeks. Betty was declining quickly but she and her daughter weren’t getting the information or help they needed. The day after we saw her we had her in the hospital getting high-dose IV chemotherapy,” Rudnick said, adding that Cedars-Sinai has several treatment options for the disease, including an aggressive and potentially curative high-dose chemotherapy/stem cell transplant protocol.

Hayden underwent a more standard regimen: a weeklong hospital stay for chemotherapy every other week for four or five months.

“If she had gone much longer without treatment, I don’t know that she would have survived. But she responded beautifully and her disease is in remission. She had a response in all the tumors and right now her MRIs are completely clean and clear. She’s doing remarkably well, pruning the rose bushes and going to dog shows,” Rudnick said. “For me, that’s incredibly rewarding.”

http://www.newswise.com/articles/after-brain-cancer-battle-orange-county-ca-resident-picks-up-active-life-where-she-left-off

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American Brain Tumor Association Recognizes Awareness Month

PRWeb
Published 9:50 pm, Wednesday, May 1, 2013

 Bright Ideas campaign to spotlight the need for answers

Chicago, IL (PRWEB) May 01, 2013

The American Brain Tumor Association today announced the launch of its Bright Ideas campaign in recognition of Brain Tumor Awareness Month.

The American Brain Tumor Association, the first and now only national organization committed to providing both patient and caregiver support services and the funding of brain tumor research, is dedicated to providing and pursuing answers. The Bright Ideas concept reflects the organization’s role in fostering breakthroughs that lead to new thinking, better understanding and more effective treatments.

“When it comes to brain tumors we don’t know who, we don’t know when and perhaps most frustrating of all, we don’t know why,” said ABTA President and CEO Elizabeth M. Wilson. “Bright ideas, however, are what lead to breakthroughs—those ‘ah-ha!’ moments that bring us one step closer to finding the answers we seek. It is our hope that the Bright Ideas campaign will increase awareness of and support for breakthroughs in our understanding and treatment of brain tumors.”

Each day, 500 people in the United States will be diagnosed with a brain tumor. They join the nearly 700,000 who are currently living with the diagnosis. And in 2013, 13,000 people will lose their lives as a result of their brain tumor. There are more than 120 types of brain tumors, which means there is no one answer to the brain tumor challenge.

The campaign is designed to engage the ABTA’s social media followers in an effort to elevate the visibility of the disease and the organization among their networks and beyond through likes, shares and re-tweets of brain tumor facts, features and photos posted by the ABTA throughout May.

To participate in the Bright Ideas campaign, follow the ABTA on Twitter (@theABTA) and like the ABTA on Facebook at http:// facebook.com/theABTA. For more information on Bright Ideas activities throughout May, visit http://www.abta.org/get-involved/brain-tumor-awareness-month.html.

ABOUT THE AMERICAN BRAIN TUMOR ASSOCIATION
Founded in 1973, the American Brain Tumor Association was the first and is now the only national nonprofit brain tumor organization providing both support services to brain tumor patients and their families and funding of brain tumor research. For more information, visit http://www.abta.org.

Read more: http://www.sfgate.com/business/prweb/article/American-Brain-Tumor-Association-Recognizes-4480590.php#ixzz2SG02z3W4