He is so lucky! The real story of PD-1 inhibitor against cancer
2015-06-22 Health First Shanghai Renji Hospital Urology Department Chen Haigo
Prichard is now back to his normal life as a brand ambassador for his family’s small winery. He was 48 years old when he participated in Dr. Tannir’s study, when he had only a 50 percent chance of getting the nivolumab drug. Fortunately, he was randomized to the trial group of checkpoint blockers.
Surgeons removed an 8-inch, 3.5-pound kidney tumor from Philip Prichard, and oncologist Nizar M. Tannir, MD, had seen larger and more aggressive tumors than that, but they were rare. The tumor had spread to his kidney. After the renal cell carcinoma spread to his liver and lungs, Philip Prichard was enrolled in a clinical trial for a new class of drugs.
Despite surgery and other treatments, Prichard’s renal cell carcinoma had spread to his liver and lungs. His last ray of hope is Dr. Tannir’s ongoing clinical trial, which is designed to test the efficacy of drugs that unleash the body’s immune system to fight cancer cells.
Two weeks after Prichard received his first injection, his previous symptoms of fever, pain, night sweats, weight loss and anemia had disappeared. After eight weeks and four injections, his main tumor had shrunk by 50 to 60 percent, Dr. Tannir said. Two years after his treatment, Prichard, 50, is so healthy that Dr. Tannir is considering whether to stop his medication. A third of the drugs he was given have been approved by the U.S. Food and Drug Administration, or FDA.
For more than a century, researchers have been convinced that the body’s immune system has great potential to fight cancer, but they just didn’t know how to unlock that potential to fight it. Today, in addition to surgery, radiation and chemotherapy for cancer treatment, immunotherapy has quickly become the fourth pillar of cancer treatment.
Many studies are now underway that hope to extend the recent results to the treatment of bladder cancer, breast cancer, Hodgkin’s lymphoma, head and neck tumors and other types of disease. Researchers are also testing the efficacy of these new drugs in combination with each other and with other therapies. Early studies have shown good results.
But as they celebrate these previously unthinkable advances, cancer experts are beginning to understand the current limitations of this powerful new therapy. While these drugs have freed some patients from cancers such as metastatic melanoma, they have not worked for others with the same disease. For specialty cancers, in the best case scenario, about 40 percent of patients show that the drugs work. This is already a huge number relative to past standards, but it is still puzzling compared to the potential that many people believe. For other cancers, the drugs have so far worked in only a small percentage of people.
Another issue is the cost: all three drugs approved by the FDA are expensive, costing more than $10,000 for a single dose in many cases, and those numbers are likely to climb.
Two years after he started treatment, Philip Prichard is so healthy that his doctors are trying to decide to stop giving him the drug nivolumab.
New advances, new costs
Over the past many years, researchers have tried a variety of ways to get the immune system to fight cancer cells, but all have had little success. The disease has a crazy ability to suppress and evade T cells from attacking foreign invaders. They tried to supercharge the immune system with drugs, but the success rate was low and brought horrible, sometimes fatal, side effects. About 10 years ago, a number of people developed drugs using a different approach, with the goal of removing “brakes” or “checkpoints” that would prevent those killer T cells from attacking healthy tissue. This new drug is called a “checkpoint blocker”.
In 2010, Bristol-Myers Squibb’s drug “ipilimumab” showed remarkable efficacy against advanced melanoma. Data from the nonprofit Cancer Institute, which focuses on immunotherapy research, showed that with ipilimumab, patients doubled their chances of surviving a year and reduced their risk of death by 32 percent. What’s even more encouraging is that some people are surviving longer. Cancer has been gone for many years. Some of the people who participated in early drug trials a decade ago are still alive today.
In 2011, the FDA approved ipilimumab for the treatment of metastatic melanoma, a treatment that has significantly improved the health of patients, but some have experienced side effects such as colitis, hepatitis, rash and neurological problems. two other drugs Prichard takes, pembrolizumab and nivolumab, were also approved by the FDA in approved by the FDA in 2014 for the treatment of melanoma. They produced better results and brought about more acceptable and manageable side effects. This year, the FDA also allowed nivolumab to be used to treat a type of lung cancer.
Research in this area exploded in 2012 when the results of earlier trials done on other kinds of cancer started rolling in. Doctors also started prescribing checkpoint blockers to certain individual patients for some cancers – often showing that the drugs were seeing results.
“Of the cancers for which drug trials have been conducted, I have not found one that has been completely ineffective for any of them. There’s no reason why the immune system should be able to detect some types of cancer but not others,” says Richard Schilsky, chief medical officer of the American Society of Clinical Oncology.”
Prichard is now back to normal life as a brand ambassador for his family’s small winery. He was 48 when he took part in Dr. Tannir’s study, when he had only a 50 percent chance of getting the nivolumab drug. Fortunately, he was randomized to the trial group of checkpoint blockers.
Since 2013, he has been receiving biweekly injections in Houston, with the cost of treatment covered by Bristol-Myers Squibb, which makes the nivolumab drug. Other than weight gain, he had no other reactions from the cancer or the drug. Looking at his scans, doctors could only see a small area that they thought might be scar tissue.
“It’s a miracle of science.” Prichard says, “If you hear someone say they don’t have to go through cancer treatment anymore, I’m proof of that.”
When doctors discovered that her melanoma had spread to her small intestine, Erin Youngerberg, a 36-year-old industrial engineer in Jersey City, didn’t have much time left. Nearly 74,000 new cases of melanoma are diagnosed each year, and almost 10,000 people die from the disease each year. Because Erin Youngerberg’s cancer has reached stage 4, she has only a 50 percent chance of surviving a year.
Earlier in 2013, in a study at Memorial Sloan Kettering Cancer Center in New York, Erin Youngerberg was started on Merck’s “pembrolizumab” drug. As a result, her tumors seemed to disappear and did not grow for two years. The only side effects were fatigue and itchy skin. “No one would say ‘cure,'” she says, “but it’s amazing how well it’s working compared to how it was when I started treatment five years ago.”
But people have only seen the healing in a few patients. Now, no one really knows why. To some extent, theories on this have emerged from a series of studies that were published in the November issue of the journal Nature. One of these studies found that the drugs would be more effective in patients who had more T cells in their tumors before starting treatment. Another study showed that treatment was more effective for patients who had more of a certain type of protein produced by T cells in their bodies.
Researchers are also trying to determine why certain cancers respond better to drugs than others. Prostate and colorectal cancers have been shown to be less sensitive to checkpoint blockers, experts say. There is also a popular theory – that checkpoint inhibitors work best for tumors that tend to have more mutations, such as melanoma.
“We think immunotherapy works best for cancers that have the most mutations because they produce more abnormal proteins that stimulate the immune system,” says Venook, an oncologist at the University of California, San Francisco.
When it comes to cost, few dare to predict how much it will cost, and Youngerberg calculates that she spends $250,000 in a year on various drugs, almost all of which is covered by her insurance or the clinical trials she participates in.
One survey found that in 2014, an estimated 139,000 Americans each spent at least $100,000 on prescription drugs in 2014. About half was spent on cancer treatments.
“I think this is an important issue that society as a whole has to face,” Tannir said, “and there has to be some consideration about how we can reduce those costs.”
But the advances and profits that oncologists, researchers and drug companies expect to make in the coming years keep research moving forward. Drew Pardoll, co-director of cancer immunology at Johns Hopkins University School of Medicine, said he expects the FDA to approve immune drugs this year for bladder cancer, kidney cancer, and Hodgkin’s lymphoma cancer. Next year, he said, the agency could approve a range of immunotherapies to treat ovarian cancer, non-Hodgkin’s lymphoma, head and neck cancer, stomach cancer, mesothelioma and a type of breast cancer, among others.
“Can immunotherapy treat all cancers? Absolutely not,” he said, “Will there be a steady stream of improvements? I’m pretty sure there will be.”
One such research advance may include the use of combinations between checkpoint inhibitors, combinations of checkpoint inhibitors and targeted drugs, and combinations of checkpoint inhibitors and chemotherapy. in a study of 142 patients published May 21 in the New England Journal of Medicine, researchers said that when these patients were treated with both ipilimumab and nivolumab for a class of malignant melanoma, a surprising response rate of 61 percent was achieved, though with greater side effects than ipilimumab alone.
“This is a really amazing moment in our field,” said Jedd D. Wolchok, associate director of the Ludwig Center for Cancer Immunotherapy at Memorial Sloan Kettering, who was also one of the researchers in that study. “It’s taken a long time to get to where we are today. It took many years of challenges to prove that immune system modulation is a standard and effective treatment for cancer.”
“But now we’ve proven it. Now the work that remains is to extend that benefit to more patients and to more types of cancer treatments.”
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