Rutgers Cancer Institute of New Jersey
195 Little Albany Street
New Brunswick, NJ 08903-2681
She's a force of nature – fiery, smart, forceful, bold, funny. Her fierce energy drives life – hers and others – forward on a focused and dynamic path. A natural redhead, her once long, straight hair is re-growing now in springy, unmanageable waves. She pulls off her cap and shakes her head a few times to show how much has grown back and how unruly and indomitable it's become. She says her husband and young son laugh at her new, wild hair, evidently sharing her joy as her life regenerates.
With persistence, courage and good humor, Carrie Best has spent most of nearly the last year-and-a-half wielding her way through a rapidly changing medical system mired in complexity. Only in the last few months has her path become clear. She now flies into Teterboro Airport in Bergen County, New Jersey from Columbus, Ohio every other Thursday morning like clockwork. Her destination is Rutgers Cancer Institute of New Jersey in New Brunswick, the only National Cancer Institute-designated Comprehensive Cancer Center in the state. Her reason for traveling is to participate in a clinical trial, one of more than 250 taking place right now at the Cancer Institute. The trial affords her the opportunity to receive a groundbreaking therapy as part of an experimental protocol before it is available more generally and makes her a pioneer in the world of cancer therapeutics.
Best is helping to test a new drug that targets a protein called programmed-death ligand one or PD-L1. "This drug is a form of immunotherapy, a different approach for treating cancer," explains her physician Howard L. Kaufman, MD, FACS, associate director for clinical science and chief surgical officer at the Cancer Institute. "The drug works by activating the immune system to fight the cancer rather than directly killing cancer cells, as occurs with chemotherapy or radiation therapy." Best, who has been diagnosed with an aggressive form of skin cancer called Merkel cell carcinoma, is thriving under the experimental regimen.
Dr. Kaufman, a leading figure in the research and treatment of melanoma and other skin cancers, says immunotherapy has been "successful against a large number of cancers in clinical trials, including melanoma, kidney cancer, lung cancer, bladder cancer and Hodgkin's lymphoma."
Traveling to New Jersey twice each month is no easy feat for Best. In Ohio, she leaves her job as a school psychologist for special needs students, her 7-year-old son Dylan, and husband Bill, who tries valiantly to preserve all family routines in her absence. She also leaves the comfort of the new home she and Bill built and which she designed during some of her worst times. "I wanted this house to be a comfort to my boys when I was gone. I wanted it to keep them safe," she says, wiping away the tears that seem to spring from a deep well. Her heart and soul went into designing their family home and she herself has derived enormous pleasure and peace there. It is her haven and also her foundation for a future that she hopes desperately to be a part of.
Best's mother, Jean Beach, is her travel buddy in more ways than the obvious ones. She has stayed closely by her daughter's side through doctors' visits, treatments and now bi-monthly plane flights. Beach is a breast cancer survivor. Twenty years ago, she did it all--surgery, radiation, six months of harsh chemotherapy--and here she sits, solid, smiling, looking good. Her positive attitude, her survivorship and emotional strength have helped to sustain her daughter through this trying ordeal.
What would you do if you woke up one morning and found a tender, grape-size lump under your arm? Well, for Best, always on the alert for cancer (She had participated in a study of daughters of women with breast cancer at the Ohio State University Comprehensive Cancer Center - The James in Columbus.), it sounded a harsh warning. She jumped out of bed and "went directly to the telephone to call The James. I hoped it wasn't cancer but I knew it was," she says.
Seven days of tests, tests and more tests confirmed that, in fact, the lump was malignant, even though the site of the original cancer could not be determined. She found herself on day number eight sitting in "the chemotherapy chair." And that is where and when Best's "incredible journey" began. "I don't belong here," she remembers thinking. "This is for sick people. I don't think it will ever really sink in--how completely my life has changed."
The New-New Cancer Therapies
For Carrie Best, and others, immunotherapy is a lifesaver. However, it doesn't work for everyone and researchers do not yet know why. It's often used when the standard treatment regimens have failed but is becoming the standard through clinical trials for some types of cancer. Howard L. Kaufman, MD, FACS, is a physician-researcher with expertise in the treatment of melanoma and other skin cancers and a pioneer in the immunotherapy field.
Q. Was Rutgers Cancer Institute of New Jersey the first site worldwide to offer this clinical trial? Why?
A. Yes. We were able to lead this clinical trial because my laboratory had contributed to the identification of PD-L1 expression in Merkel cell cancer samples. The Cancer Institute is the ideal place for such a study because we have a large patient population with skin cancer; we have a comprehensive team of physicians, nurses and pharmacists with an interest in advanced skin cancer treatment; and we have the research infrastructure to support important clinical trials, such as this one.
A. We have enrolled six subjects at Rutgers and the trial is still open to recruitment. The total goal is 84 patients and the study will be open internationally throughout the U.S., Europe, Japan and Australia.
Best, a determined and action-oriented person, was a 911-police dispatcher for 13 years, working 12- to 16-hour days, reacting quickly and decisively to other people's emergencies. In 2005, she and Bill, an undercover police officer, married and in 2007, Dylan, their IVF baby, was born. In the meantime, Best was shifting gears professionally, laying the groundwork for a life without shift-work, ongoing crises and constant exhaustion, a life where she could "be there" for their child. She stayed on the job and in her off hours studied school psychology--all while pregnant with Dylan. The process was "brutal," she says, but she earned her master's degree in 2008 and subsequently began a job working with special needs children, a job she loves.
Springing into action was very much a part of Best's training and is still an important aspect of her personality. Deeply distressed by the lack of a definitive diagnosis, she jumped onto the Internet, pounding away at her online research "two, three, sometimes four hours night after night, while Dylan slept." She was intent on finding out what was happening to her body and understanding the technicalities of scientific research in the field. "I knew my cancer was really bad and that my chances were slim from the get-go," she says.
Merkel cell carcinoma seemed the most likely diagnosis and it is not a good one. Best has fair, freckled skin and in her younger years loved lying in the sun. In her 20s and 30s, she had a series of questionable skin growths removed. Merkel cell carcinoma is a rare cancer, often linked to sun exposure. About 2,000 cases were diagnosed in the U.S. in 2014, compared with more than 70,000 new cases of melanoma.
"The number of new cases has doubled in the last decade. The reason is not clear but may be related to excessive sun exposure since many Merkel cell cancers begin in areas exposed to the sun and occur within sun-damaged skin," explains Kaufman, who is also a professor of surgery at Rutgers Robert Wood Johnson Medical School.
"The Merkel cell polyoma virus was discovered in the last decade and appears to be present in 80 percent of Merkel cell cancers and may also be contributing to the disease," he continues. "Pathologists may also have become better at diagnosing the disease."
Best not only did an enormous amount of online research but contacted physicians and researchers worldwide who are working in this field, and traveled to The University of Texas MD Anderson Cancer Center for a consult. She read everything available on pertinent clinical trials, consulted with a genetic oncologist, looked into gene therapy. She was desperate to find a life-saver and time was running out. "I kept thinking, 'If only I knew what the primary site was, if only I knew,'" she says.
Best participated in a clinical trial at The James in Ohio. When the first set of scans showed her cancer had progressed, Best voiced her discouragement over not knowing the primary site of the cancer. She had been told that information would open doors to clinical trials. She was advised that a new test--with the capability of delineating an individual's particular cancer molecular ID--could pinpoint the cancer's origin with 96 percent certainty. However, she was told the test was very expensive. Fighting for her life, Best decided on the spot that she needed to have this test in order to move forward. And, indeed, it gave her that vital piece of information--and her insurance ended up paying for the test. Not only did it confirm that Merkel cell carcinoma was what she was dealing with (malignant cells most likely traveled from her upper arm to a lymph node in her armpit), but it detailed the specific mutations of her tumors.
Best now had the information she needed to proceed. She sent hundreds of emails to clinical and laboratory researchers, oncologists and other physician-specialists, and even a robot-builder working on cancer, saying, "These are my genetic mutations. I'm fighting for my life. Can you provide me with any information?"
Most of her emails were not answered, but her plea for help elicited responses from several pivotal sources. And lo and behold, she hit pay dirt. It was the friend of a friend of a friend process, but it got her to the right place.
One respondent wrote back: "My research is not relevant, but I have a friend at Sloan Kettering whose work is relevant, and I am forwarding your email to him." The following Monday, Best and her husband were on their way to Memorial Sloan Kettering Cancer Center in New York to meet with a team led by a physician-scientist focused on the identification of novel mechanisms of resistance to current cancer therapies. It turned out to be one of the most meaningful steps in Best's journey. The group advised her that she needed to get into an anti-PD-L1 trial. "Our trial won't open for about two weeks," she was told, "but you don't have two weeks to wait."
Creating, testing and proving the next generation of cancer drugs is what this story is largely about. Best was told some good news, for once. She was referred by the Sloan Kettering team to Rutgers Cancer Institute of New Jersey and specifically to Dr. Howard Kaufman, whose anti-PD-L1 trial was already up and running.
"My lab has looked at PD-L1 expression in Merkel cell carcinoma tumors and found nearly 100 percent of these cancers overproduce PD-L1, suggesting they might be very responsive to treatment with agents that block PD-1 or PD-L1. In this study we are using a new PD-L1 antibody [a blood protein produced in response to and counteracting a specific substance that the body recognizes as alien, such as bacteria and viruses] in patients with metastatic Merkel cell cancer who have failed standard chemotherapy," he explains. "Patients are treated until they fully respond, clearly do not respond or develop side effects that prevent further treatment."
Flying into New Jersey bright and early on the following Monday, Best was full of renewed hope. But she had to take one small step backward before she could proceed with a giant step forward. Testing was required to determine if she was eligible for the PD-L1 trial.
Requirements for inclusion in the trial are stringent, she was informed. She would have to have at least one of three biomarkers most frequently associated with Merkel cell carcinoma. After her blood was drawn and she had been counseled about the trial, Best went back home to wait a week for her test results. She was "on pins and needles." If this opportunity fell through, she knew the realities of terminal illness--little time and no real possibilities left--would come crashing down on her.
Best had been there before. While undergoing chemo in early in her journey, she was told it was no longer working, and her odds of recovery were less than one percent. "At the time, I was camping, hiking, working every day. I had lots of energy," Best remembers. She thought about her son. "Dylan is such a happy little boy. I wasn't ready to yank his childhood away from him."
"That was the worst day of my journey," she continues, adding her hope was taken away. At the time, Best and her husband were building their new house and living with her parents. She remembers crying all weekend, but her mother's advice snapped her out of her despair. "You need to get over this," she said.
Now Best was waiting for the news that she hoped would jumpstart her recovery. She had been having migraine headaches, which she attributes to her enormous stress, and had gone for a massage, leaving her cell phone in the car. When she returned to the car, "I had a hundred million messages," she says.
She has Bill's message committed to memory: "Rutgers called," he said. "You have the biomarkers and you are in." "It was a huge moment for me," she says, tearing up. In less than one week, she was a patient of the Cancer Institute of New Jersey in New Brunswick and the country's (and possibly the world's) first participant in a clinical trial of a drug targeting PD-L1 for Merkel cell carcinoma.
Kaufman explained to her that she had tested positive for all three biomarkers for the disease, and was a good candidate for treatment with the drug. She clearly remembers him saying: "I'll see you in the morning. Let's go make some history."
She and her mother exchange looks, each with a private memory of that moment. "My mom and I were giddy," Best says. "My mind-blowing panic attacks and drowning fear" zoomed south to a slow simmer-- as she turned her care over to Kaufman and his team. "We're moving into a new age of cancer treatment," she says. "You need to know your genetic mutations to get proper treatment and you need to advocate for yourself."
Heady as the news of her new treatment was, Best still had to worry about the practicalities of paying for her flights to and from New Jersey twice each month and the hotel room needed for an overnight stay every two weeks. Luckily, her online research led her to the Corporate Angel Network, an organization of 500 U.S. corporations, which arranges for cancer patients, and bone marrow donors and recipients who are ambulatory, to fly free for medical care in empty seats on corporate jets. The Network, which has no limits on use for flights within the U.S., arranges more than 3,000 flights a year. In addition, Best has relied on the American Cancer Society's service that arranges free or very low cost hotel rooms for those needing medical treatment far from home.
Best, whose cancer was so aggressive that her tumors had doubled in size and spread even after long and aggressive chemotherapy, is now hoping for a lifetime of remission. "I have chased this remission all over the country," she states, "and on the way, I've learned to be persistent, dogged, aggressive."
"Don't be passive," she warns. "Ask hard questions. If your doctor doesn't like that, move on to another doctor."
Kaufman says immunotherapy is "such an exciting area of research because it appears to induce durable, long-lasting responses in patients when it works." Why it works sometimes and not others is still not known.
He explains that interleukin-2, another immunotherapy in use since 1992 for patients with metastatic melanoma or kidney cancer, "has been associated with responses in 17 to 20 percent of patients. Long-term follow-up of the patients indicates that a subset may be free of disease for as long as 20 years after treatment." In other words, these patients may have been cured of their metastatic cancer.
After just three treatments with PD-L1, Best's scans were clear--no tumors visible. She was not expecting such a quick, positive response. The day that Kaufman gave her the good news "was another giddy day," she says smiling. Her gratitude, she says, is overwhelming, both for the drug that has turned her life around and for the empathy, kindness and good care given by Kaufman and his team.
As part of a 900-member Google group of people with a diagnosis of Merkel cell carcinoma, Best frequently sees postings about those who have died. The information affects her strongly--almost as if she actually had met them and become friends.
Her blog--posted on CaringBridge.org--gives an informative and passionate account of what she has encountered on her "travels." While her husband and friends find it "too raw, too real," more than 6,000 readers wait for Best's posts. She has become a leader among patients battling metastatic cancer.
In fact, as we walk together out of the Cancer Institute room where several patients sit with friends and relatives while receiving treatment, a man calls out to say hi to Best. "I'll be back in a couple of minutes to chat," she calls to him. To me, she says happily, "He's in this clinical trial because of information I posted on a cancer blog." And she has been writing a chronicle of her journey. "It's for my son," she says, "who was so little when I got sick. I wanted him to know how hard I have fought to stay here with him."
Simply put, her message for those with cancer is: "There's always hope. Be your own advocate. This is the dawn of a new era of cancer treatment. It is the best of times." ■