WAR ON CANCER

ON THE CUSP OF A CURE

Lehigh Valley plays key role in trials that have pulled some from brink of death
BY SAM KENNEDY
OF THE MORNING CALL

Richard Dey, a 69-year-old retired plumber, had a round of X-rays and other tests, and now he’d find out the news — good or bad.

Dey and his wife, Patti, of Washington Crossing, Bucks County, were ushered into the exam room of Dr. Suresh Nair, head of oncology at Lehigh Valley Health Network. The couple exchanged greetings with the doctor and took seats under the wash of fluorescent lighting — Dey on the padded chair with paper covering that crinkled with his every move.

“We were just going over your scans,” Nair said casually, moving the conversation along to the matter at hand.

If Richard Dey was nervous, he didn’t show it. But Patti Dey was up, leaning over Nair’s shoulder to get a better look at the laptop screen displaying the ghostly before-and-after images of her husband’s lungs.

Photo by April Bartholomew
Dr. Suresh Nair points out the disappearance of a tumor on Richard Dey's lung scan as Dey and his wife, Patti, look on.

In the fall of 2011, a toenail on Dey’s left foot became badly infected. He assumed it was a fungus, but a biopsy proved otherwise: melanoma, skin cancer. The toe was amputated. As a precautionary measure, the lymph nodes in his left groin were surgically removed too. All was well for about a year and a half, when the shape-shifting melanoma suddenly reappeared, this time in the form of multiple lung tumors.

“I can’t help you anymore,” his Philadelphia area surgeon told him. The final stage of cancer — the one bracketed on one end by death — is Stage 4. This is what he had.

“I figured, well, it’s pretty close to being over now,” Dey said. A reasonable assumption, but it turned out to be wrong.

If Dey was incredibly unfortunate to have been diagnosed with Stage 4 melanoma, he was also extremely lucky to have been diagnosed when he was — and where. He sought entry into a clinical trial just in time to snag a coveted spot in the one Nair was about to start at Lehigh Valley Hospital-Cedar Crest, just over an hour’s drive from his home. Thanks to Nair’s efforts, LVH was one of eight sites nationally selected to participate in a clinical trial testing the effectiveness of combining two new immunotherapy drugs, nivolumab and ipilimumab.

Until recently, modern medicine had come up with but three ways to treat cancer: excising it (surgery), obliterating it (radiation) and poisoning it (chemotherapy). But immunotherapy is something completely different — a revolutionary approach giving rise to talk of a miracle cure.

Surgery, radiation and chemotherapy are each in their own ways brutal, direct assaults on cancer that can leave survivors physically, mentally and emotionally diminished, whereas immunotherapy coaxes the body’s immune system to do the fighting, often with minimal side effects.

Dey submitted to 41 intravenous infusions of experimental immunotherapy drugs. That he even managed to come back again and again for so many infusions was itself a notable achievement. For just about as long as Nair had been in oncology, which was long enough for his hair to fade from black to white and his name to become known outside Pennsylvania, a diagnosis of Stage 4 melanoma left little room for hope. The only real question was one of time — how much of it was left — and all too often the answer was in increments not of years, but months.

And yet here was Richard Dey, back one day early this year, more than four years after his diagnosis, for another checkup. As Patti looked on, Nair pointed to the place on one of the lung scans where a tumor had been.

“That’s gone.” He continued pointing here and there. “That’s gone. That’s gone. This was the biggest one. It’s gone.”

Dey’s tumors had melted like ice cubes. His cancer was, as Nair put it, gone. The worst reaction over the course of his treatment was a thyroid problem. “It’s a good trade-off for being cured,” he told Nair.

Now, the doctor suggested, the Deys could go to Florida for the long-deferred vacation the couple hadn’t been sure they’d ever be able to take.

Whether melanoma or leukemia, lymphoma or lung, cancer in all its myriad manifestations shares a single common denominator: an uncontrollable growth of an abnormal cell. Mitosis, or cell division, which is an elemental function of all life, turns deadly.

In his State of the Union address in January, President Barack Obama called for a new, national “moon shot” to eliminate cancer, pledging $1 billion to jump-start the initiative. The terminology optimistically called to mind a previous president’s challenge, met with success, to put a man on the moon by the end of the 1960s.

The more common cancer metaphor, however, is hardly so positive. The nation is said to have been at war with cancer at least since President Richard Nixon signed the National Cancer Act of 1971, and perhaps since President Franklin D. Roosevelt approved creation of the National Cancer Institute in Bethesda, Md., in 1937. Given the other “wars” — on terrorism, drugs, poverty — this use of this term might seem hackneyed if not for the fact that cancer killed about 600,000 Americans last year alone, or more than died in all of World War II. Clearly, cancer is at war with us.

Though now, quite suddenly and dramatically, the momentum appears to have shifted in our favor, according to those leading the counterattack.

Immunotherapy of the kind used to treat Dey’s melanoma has also shown promise in a variety of other cancers and on people of all ages. Consider the remarkable turnaround of President Jimmy Carter. In August of last year, Carter announced that after surgery for a small mass on his liver, doctors found he had cancer and it had metastasized, or spread, to his brain. Then in December came the head-spinning news that the 91-year-old was cancer-free and teaching Sunday school once again after undergoing treatment with an immunotherapy drug called pembrolizumab.

“The power of the immune system is that it has memory,” Dr. Jedd Wolchok of the Memorial Sloan Kettering Cancer Center in New York told a packed auditorium at LVH-Cedar Crest in December. “This is truly curative.”

At the same time, a completely different approach, eagerly anticipated for more than a quarter century, is beginning to fulfill its promise as well. It’s called targeted gene therapy, and it attacks cancer at its genetic source.

“We are on to something not just big, but something huge,” said Dr. Sanjiv Agarwala, chief of medical oncology and hematology for St. Luke’s University Health Network in Fountain Hill. Like Nair, Agarwala has gotten an advance look at the new treatments through participation in clinical trials.

At this turning point in the war on cancer, the Lehigh Valley is perched on the front lines, with an upfront view of the action. Not only are doctors such as Nair and Agarwala involved in important scientific work, but this year LVHN entered into an alliance with Memorial Sloan Kettering. The arrangement allows LVHN doctors to collaborate with and learn from peers at Memorial Sloan Kettering, the world’s oldest cancer research and treatment center. Memorial Sloan Kettering benefits too by expanding its clinical trials to a larger population.

Breakthroughs at the molecular level of cancer research, it turns out, are reverberating far beyond the laboratory, spurring innovation and collaboration at the institutional level.


Discoveries and advances

On the one hand, immunotherapy seems to have come out of nowhere. In Siddhartha Mukherjee’s Pulitzer Prize-winning history of cancer, published just six years ago, immunotherapy doesn’t even rate an index entry. On the other hand, the first indication that the immune system could be coaxed into fighting cancer was documented more than a century ago by William Coley, a surgeon at the New York Cancer Hospital, the precursor to Memorial Sloan Kettering.

Coley noticed one of his cancer patients experienced a complete remission following an unrelated bacterial infection. Over the next several decades, Coley injected the bacteria, which became known as Coley’s toxins, into more than 900 cancer patients, most of whom had inoperable sarcomas, or tumors. About 10 percent of the patients were entirely cured, apparently because the toxins somehow jogged the immune system into action. Even so, lacking a theoretical framework to explain the underlying biological mechanisms at work, Coley’s insights were widely dismissed and nearly forgotten.

Photo courtesy of Memorial Sloan Kettering
William Coley was a surgeon at the New York Cancer Hospital, the precursor to Memorial Sloan Kettering. He documented more than a century ago that the immune system could be coaxed into fighting cancer.

Not until the end of the 20th century did researchers give immunotherapy a second, serious look. In the mid-1990s, James Allison led a team of scientists at the University of California, Berkeley Cancer Research Laboratory that determined a biological molecule called CTLA-4 regulated immune system T cells. Allison theorized, correctly, that CTLA-4 was inhibiting T cells from attacking cancer cells. In a landmark paper published in 1996, Allison’s team showed that blocking CTLA-4 could slow and even stop tumor growth in mice. The findings launched a race to develop drugs for human use.

But the race was a marathon, and it was still in progress in 2008 when Bill Cantwell, a landscaper in Mahoning Valley, Carbon County, noticed an odd mole on his thigh. It seemed to be morphing by the day. His wife, Crimsin Kern, persuaded him after much prodding to see a doctor who, after tests, informed him he had nodular melanoma.

“It’s one of the rarest and deadliest, but I’m here seven and a half years later,” Cantwell, then 47, said in December.

After his diagnosis, Cantwell underwent the established course of treatment, which had varied little in decades. The mole on his thigh was removed surgically, as were lymph nodes in his groin. Stubborn and fun-loving, he remained positive. But a year and a half later, the cancer resurfaced in the scar tissue on his thigh, prompting additional surgery, including the removal of more lymph nodes.

Cantwell gave up his landscaping business, taking an office job at a payroll company, in part for the health insurance. “That was the hardest time,” Kern recalled. “It was mentally challenging for him to accept his life was different. … He was stuck indoors.” But not one to despair, Cantwell soon came to genuinely enjoy his new line of work, she said.

After the surgeries in 2010, Nair put him on a regime of interluken 2 via intravenous infusions. A first-generation immunotherapy in use since the 1990s, IL 2 is a synthetic form of a protein the body produces naturally. It works by increasing the immune system’s production of T cells and so-called natural killer cells, curing about 1 in 10 melanoma patients.

Bill Cantwell (left) with his wife, Crimsin Kern.

“We were making slow, steady progress — too slow when you are dealing with Stage 4 cancer,” Nair said.

Nair was eager to get his hands on the next generation of immunotherapy drugs which, after more than a decade of painstaking development, were finally ready to test on human melanoma. Having led the National Cancer Institute group that oversees early-phase clinical trials, he was well aware of the drugs’ potential. And so, under his direction, LVHN applied for and won an NCI matching grant that helped cover the cost of expanding the network’s clinical trials program, mostly by hiring specially trained nurses.

Cantwell seemed likely to be among the first beneficiaries. In 2013, after more than two healthy years, his cancer reappeared, this time on his liver. It was categorized as Stage 4-M1c, which signifies the final stage of the final stage. The prognosis could hardly have been bleaker, though advance word of immunotherapy drugs offered hope of a miracle.

In December of that year, Science magazine named immunotherapy its “breakthrough of the year,” exulting, “The field hums with stories of lives extended.”

Cantwell wanted to be part of Nair’s upcoming Phase 2 clinical trial testing two drugs concurrently. The trial, however, had been designed for patients who had cancer in more than one organ, and Cantwell no longer did — or so it seemed at the time, based on his scans. He was ineligible because of the apparent success of his earlier interventions. He had cancer, just not enough of it.

If Nair couldn’t get Cantwell onto the two immunotherapy drugs, he could at least get him onto the one — ipilimumab, sold under the brand name Yervoy by Bristol-Myers Squibb — that had by then received approval by the U.S. Food and Drug Administration. Like IL 2, ipilimumab stimulates the immune system, but in a novel way — by disabling CTLA-4. Think of the immune system as a car. IL 2 slams the immune system’s accelerator to the floor, while ipilimumab releases the brakes. In this hyper state, the immune system attacks cancer cells.

PHOTO GALLERY

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Nair also hit Cantwell’s cancer with targeted gene therapy after finding it contained a mutated “BRAF” gene that drives abnormal cell growth.

Cantwell’s tumors disappeared. Once again, he was pulled back from the brink. In 2014, the FDA approved a new immunotherapy drug — pembrolizumab, or Keytruda, from Merck & Co. Pembrolizumab works by disabling a protein called programmed death-1 that makes cancer cells invisible to the immune system. Nair started Cantwell on this “anti-PD1,” too.

Cantwell’s final reprieve lasted 10 months. Then, through 2015, his condition deteriorated as his cancer spread to his abdomen, his throat, his brain. He underwent gamma knife radiosurgery, a type of radiation therapy, to treat a brain tumor. He also started on a second anti-PD1 called nivolumab — the other of the two drugs in the clinical trial from which he had been excluded two years earlier. Clearly, neither Cantwell nor his wife, Kern, was ready to give up.

Increasingly desperate, Kern spent countless hours studying articles in medical journals. She pitched alternative treatments to Nair, who was always willing to consider her suggestions. When she requested one of the experimental treatments she’d read about — ipilimumab alongside stereotactic radiation — he agreed to try it, and it did seem to help for a little while.

“He listens to the patient,” Kern said of Nair. “He would never have forced any of this stuff on Bill, but he knew this is what Bill wanted.”

In his final year, Cantwell’s health charted a violent course of ups and downs, but the overall, downward trajectory was clear. In August, an adverse autoimmune response triggered colitis, renal failure and respiratory failure. “Everything was shutting down,” Kern said, and then he bounced back one more time — until the cancer spread to his brain in December.

Cantwell’s last hospital visit was in early February. In the later stages of his treatment, he had managed to try just about all of the latest immuno- and targeted gene therapies. But despite his willingness, he did not enter any clinical trials. Perhaps these therapies, particularly those combining two drugs, would have worked better for him earlier on, if they had been approved at the time, Nair said. Cantwell died on the morning of Feb. 20.

Kern called the oncology nurse who works at Nair’s side at 7 a.m. to let her know. Minutes after they hung up, Kern’s phone rang. It was Nair. He too was grieving.

“I was on the phone with him for quite a while,” she said. “We rehashed everything. He said that there was nothing else that could be done.”

VIDEO GALLERY: DR. NAIR AND HIS PATIENTS

Larry Fegely (left) of Whitehall Township and Tim Grube of Nazareth.

Cancer doctor

In 2014, LVH became the second site in the nation to participate in the Phase 3 clinical trial known as BMS-218, testing ipilimumab and nivolumab concurrently. The timing couldn’t have been more fortuitous for Larry Fegely of Whitehall Township and Tim Grube of Nazareth.

Fegely, 66, is an unassuming Vietnam War veteran who worked for 42 years for Buckeye Partners in Lower Macungie Township. Two years ago, he bumped his head in his shed. The wound on his scalp stubbornly refused to heal, morphing into a mushroom-like growth that occasionally bled. Then a gland below his left cheek swelled, forming a lump on his face. Still, he ignored these signs until his dentist persuaded him to see a doctor. Scans found 20 lung tumors and a mass on his salivary gland. He had advanced melanoma.

“Eventually, I got to Dr. Nair. Thank God for that,” Fegely said.

Though he instantly understood the gravity of his diagnosis, he didn’t dwell on it, he said, perhaps in part because he had faced and somehow managed to escape mortal danger before. (Once, in Vietnam, he sprained his ankle jumping out of a helicopter. While he was recuperating, the man who replaced him was killed in action.) But he also drew strength from Nair himself. “He was so determined. He was so positive,” Fegely said. “I didn’t really think about [dying].”

Grube had been diagnosed with melanoma the year before, shortly after his 50th birthday, after his wife noticed changes in a mole on his back. He underwent three surgeries: one on the mole, and two to remove lymph nodes in his groin. Then he tried a first-generation immunotherapy similar to IL 2 called interferon. “That was really a rough drug; I slept 14 hours a day for a month,” said Grube, a father of three who manages a small stationery business in Bethlehem.

But the cancer came roaring back. A positron emission tomography scan found tumors in his lungs and liver. “I was about as serious a case as you can expect,” he said. “I was two to three months from being gone.”

Nair immediately enrolled Fegely and Grube in his trial and began treatment. Indeed, the doctor was no less eager than his patients to get started.

Oncology, the field of medicine devoted to cancer, might seem like an especially depressing line of work. But Nair wears a smile and laughs easily. Those who know him — his wife, Terri Nair, among them — describe the mild-mannered doctor as perhaps the most optimistic person they’ve ever encountered. “He’s even that way at home,” Terri confirmed. She said he derives hope, in part, from his clinical research and the prospect of finding a cure.

The story of Nair’s journey to LVH-Cedar Crest begins in India, where he was born, and passes through Penn State University, where on Saturdays in the fall the soft-spoken doctor is transformed into a rabid Nittany Lions football fan.

Photo by Harry Fisher
Lehigh Valley Hospital oncologist Suresh Nair was key to establishing a relationship with Memorial Sloan Kettering so that Lehigh Valley patients could take part in cutting-edge clinical trials.

He spent the first years of his life in a small village on the southern tip of India, attending a Catholic boarding school where instruction was in English. After his father, who had studied at Iowa State University to become a chemist, found work in Pennsylvania, his family settled in rural Dallastown, York County. “They had me try out for wrestling because I was small-framed, but I quit after a week,” Nair recalled with a laugh. “It was too rough.”

Nair’s forte was academics. After graduating from Central York High School in 1979, he went on to Penn State. There, he developed his love of football, and by the end of his freshman year, his foreign accent was gone. “Penn State was a big part of my acclimation to this culture,” he said.

He graduated magna cum laude from Penn State’s accelerated pre-med program in 1982, and from Jefferson Medical College in Philadelphia in 1984. After a residency at Geisinger Medical Center in Danville, Montour County, he became a fellow in the oncology department at the University of Pittsburgh. Coincidentally, his fellowship at Pitt overlapped with that of Agarwala, now the head of oncology at St. Luke’s. Today, the two are friendly rivals.

In 1990, Nair returned to Geisinger. It was there, during his residency, that he met his future wife, Terri — “a Pennsylvania Dutch girl,” he said, chuckling. She was a nurse to whom he sold some Penn State football tickets. But after their romance blossomed, he had to clear his conscience: He had sold her the tickets at face value even though he had gotten them for free, he confessed.)

During his decade-and-a-half tenure at Geisinger, Nair climbed in rank while establishing a name for himself as a deft clinician with a penchant for research. He published peer-reviewed research articles at the rate of two, three or more a year, even as he managed to win a Geisinger award for highest patient satisfaction.

By the mid-2000s, Nair’s reputation had spread beyond Pennsylvania. After he became chairman of a regional cancer group based at Mayo Clinic in Rochester, Minn., officials at Mayo tried to entice him to move to the clinic. But Mayo was hardly his only suitor. In the end, Nair picked LVHN. He said he wanted to be part of something new, and LVHN promised him the opportunity to lead the transformation of its oncology department. Plus, it was in the right state — the one that had become home.

Nair has Penn State season tickets for himself, his wife and their two children — one is a Penn State alum and the other a Penn State student. As his patients and their caregivers testify, Nair’s demeanor is powerfully calming and reassuring. He’s their talisman. And yet he’s also a man who has to make life-or-death decisions. Some patients get better. Some don’t. It takes a toll, even on him.

He does his screaming at Penn State football games. “It recharges me,” he said.

At LVHN, one success set the stage for the next. The NCI grant helped the network beef up its clinical trials infrastructure, and that expansion gave confidence to the pharmaceutical companies, which help to decide who has access to developmental drugs. In the meantime, Nair launched an oncology fellowship program. By the time Memorial Sloan Kettering began its search for regional partners, all the pieces were in place at LVHN. One of those pieces was Nair himself.

Photo by April Bartholomew
Lehigh Valley Hospital has entered into an alliance with Memorial Sloan Kettering, allowing Dr. Suresh Nair (right) and other doctors to collaborate with peers at the world's oldest cancer research and treatment center.

“Suresh has been integral to this,” said Memorial Sloan Kettering Deputy Physician-in-Chief Richard Barakat, who helped vet LVHN. “We wanted a very substantive relationship. … He really shared the same vision.”

In Nair, Memorial Sloan Kettering’s leadership saw a kindred spirit. “He was a clinical researcher,” Barakat noted.

The clinical trial in which Dey, the retired plumber, participated was not an unqualified success. It comprised four LVHN patients, two of whom died. But by the time Fegely, the Vietnam vet, and Grube, the father in his early 50s, were in the BMS-218 trial, doctors had gained a better understanding of how to use ipilimumab and nivolumab together.

Fegely started on IL 2, administered intravenously at room temperature. “I would get the chills so bad I’d start to shake, and they’d put two or three blankets on me,” he said.

He later switched to ipilimumab and nivolumab. “I was pretty lucky. I had hardly any side effects at all,” he said. The worst was a serious bout of dehydration, which Nair detected during a routine visit. “He actually wheeled me down to Admission,” he said.

Grube followed a similar course of treatment, though his side effects were more severe than Fegely’s. Twice he was hospitalized with liver problems that were eventually resolved through the use of steroids. All the while he kept working, though he could no longer participate in his adult soccer league.

Often an assistant would have to tell Grube and the other patients in Nair’s waiting room that Nair was running behind schedule. But Grube said he wasn’t bothered, and no one else seemed to mind too much either, because they all understood and appreciated how Nair works — focused on the patient before him.

He ignores distractions, forgets the clock. Indeed, he is loathe to turn to his laptop during an appointment, even it means he has to attend to the inevitable administrative details of modern medicine later — or earlier. Terri Nair said she is often awakened at 5 a.m. to the sound of her husband dictating to a voice recorder. On a good day he’s home from work at 8 p.m., but 10 p.m. is more likely.

“He just feels the patients deserve all of him,” she said.

Grube said of his appointments with Nair: “I would go in feeling bad, and I would come out feeling marvelous. Without any medication, you go out feeling like a brand new person.”

Within weeks of starting immunotherapy, the disfiguring lumps on Fegely’s head and face began to shrink. They had vanished after a couple of months. “Nobody could believe it,” he said.

Later, Nair switched Fegely to pembrolizumab, the drug credited with saving Carter’s life. Fegely’s final infusion was in December. By then, the tumors in his lungs were gone too, leaving behind only scar tissue that would dissipate with time. “It was like a miracle,” Fegely said.

Grube’s cancer went into remission too, and he started playing soccer again, though he recently experienced a relapse. In April, scans detected two cancerous growths — one between his lung and diaphragm and the other on his brain — and now he’s back on the nivolumab.

“I feel great, and I have high hopes,” he said last month.

Collaborative approach

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PHOTO GALLERY: MEMORIAL SLOAN KETTERING CANCER CENTER IN NEW YORK CITY

Ahandful of comprehensive cancer centers are renowned nationally and even internationally. Among them are the Mayo Clinic, the University of Texas MD Anderson Cancer Center in Houston, the Dana-Farber Cancer Institute in Boston. The granddaddy of them all is Memorial Sloan Kettering, which was founded as the New York Cancer Hospital in 1884.

MSK’s main campus is a cluster of buildings on Manhattan’s Upper East Side, though the center comprises about a dozen locations across the city, not including an additional half dozen in the surrounding suburbs. It employs nearly 14,000 scientists, doctors, nurses and other staff, many of whom are directly involved in more than 800 clinical trials underway at any given time.

MSK’s newest facility is the Josie Robertson Surgery Center, which opened this year. The pencil-thin 16-story gleaming tower with sweeping views of the East River is devoted entirely to outpatient operations. Its 12 operating rooms were designed for specific cancers and procedures, such as breast cancer reconstruction.

Much of MSK’s research occurs in a cluster of buildings a few blocks to the north. There, the floors are filled with men and women in lab coats who conduct experiments on cancer cells in petri dishes, study the cells under high-powered microscopes, decode the cells’ genetic makeup through ultra-fast computer processing, and so on.

MSK’s single-minded focus on cancer translates into advantages of scale. Take, for example, its pathology department. Samples of human tissue flow into the department not only from MSK’s own operating rooms, but also from those of other hospitals throughout the city, its suburbs and sometimes even much farther afield. Aisle upon aisle of pathologists stand arms-length apart at dissection tables, scalpels in hand, slicing into bloody, disembodied tumors. If MSK is better at identifying rare cancers — and it is — that’s because it sees more of them.

Among MSK’s highly specialized divisions is the Ludwig Center for Cancer Immunotherapy, which includes a number of prominent researchers, including Wolchok, the doctor who gave the lecture at LVH-Cedar Crest in December. Wolchok designed the clinical trials in which Nair participated, testing ipilimumab and nivolumab concurrently. Nair describes Wolchok as “a rock star” in the field of cancer research. “I love the way his mind works,” Nair said.


The center is coordinating efforts to move beyond melanoma. Already, in clinical trials, immunotherapy has proved to be effective in the treatment of a variety of other cancers, including lung, bladder, and head and neck cancers.

If immunotherapy has a drawback, it’s the cost. Generally, patients who participate in clinical trials don’t have to pay anything. But once a drug is approved by the FDA, insurance companies bear most of the cost. Pembrolizumab, used on Carter, costs more than $10,000 a month. Prolonged treatment with multiple drugs can easily run into the hundreds of thousands of dollars.

For LVHN, selection as MSK’s second Alliance partner — the first was the Hartford HealthCare Cancer Institute, in Connecticut — was a coup. It was announced last August after nearly two years of due diligence by both sides.

“Every major hospital in the Northeast wanted this slot,” Nair said.

Immunotherapy is but one of the fronts where MSK is making advances. Another is targeted genomic therapy.

Targeted genomic therapy turns cancer taxonomy on its head. Historically, cancers affecting a certain part of the body were classified together. Advances in the field of genetics, however, have revealed that sometimes two anatomically unrelated cancers are similar at the genetic level. Identify the Achilles’ heel of the one, and you might be able to defeat the other, as well.

To find these genetic similarities, researchers at the Marie-Josee and Henry R. Kravis Center for Molecular Oncology, which MSK launched in 2013, are sequencing the DNA of a vast archive of tumor specimens and tissues. It’s part of a project MSK calls IMPACT, for integrated mutation profiling of actionable cancer targets. Already, IMPACT has prompted a more efficient and faster approach to conducting clinical trials called “basket trials.”

In a basket trial, rather than test a drug against one kind of cancer, researchers test it against a multitude of cancers sharing a particular genetic mutation — such as the BRAF mutation that was in Cantwell’s melanoma but is also found in some forms of lung, breast and other cancers.

In this way, researchers expect to give new life to old drugs that were previously shown to be effective on just one kind of cancer or, worse, that were shelved because they seemed at the time to work on too few patients.

LVHN and MSK’s other alliance partners — a third, the Miami Cancer Institute at Baptist Health South Florida, was announced in February — will help MSK meet the challenge of identifying appropriate clinical trial participants, something made that much harder by targeted genetic therapy’s specificity. “It’s really pretty restrictive,” Barakat explained. “You’re drilling down into a smaller and smaller subset of patients that will meet the eligibility.”

Nair said LVHN’s partnership with MSK represents “a sociological change.” Similarly, MD Anderson, MSK’s main rival to the title of top-ranked cancer center, has joined forces with Cooper University Health Care in Camden, N.J., to form the Cooper-MD Anderson Cancer Center, with locations throughout the greater Philadelphia area.

“In the past, organizations didn’t trust each other enough” to collaborate, Nair said. But now, LVHN doctors are on “tumor boards” in which they discuss and debate treatment with colleagues at MSK, and they are being trained in new techniques such as the MSK-developed “sentinel node mapping,” used in the treatment of endometrial, cervical and uterine cancers. About 10 MSK-led clinical trials have been extended to LVHN so far, including several basket trials for experimental targeted gene therapies, and more are planned. “The more, the better,” Nair said.

Photo by Harry Fisher
Rebecca Schlegel started treatment in 2012 for Stage 4 melanoma. 'I didn't know what to do,' she said. 'I just cried.'

In 2012, as Nair was getting ready to participate in an immunotherapy trial for the first time, 26-year-old Rebecca Schlegel of Easton snagged a zipper on a mole on the back of her ear. Her ear began to bleed. It didn’t stop. She was working at the time as an office assistant for Bottom Dollar, and her manager commented on the blood.

“I was terrified and embarrassed at the same time,” she said.

Schlegel, a single mother living with her two young daughters, two cats and a boyfriend in a small, second-floor walk-up apartment with baby gear and toys under foot, went to the hospital. Tests found a tumor in her brain — which explained her recent headaches — and three cancerous growths on her left lung and two on her liver. She was told she had Stage 4 melanoma. Her thoughts immediately turned to her daughters, then ages 5 and 2.

“I was speechless,” she said. “I didn’t know what to do. I just cried.”

Her outlook improved after she met her oncologist, Nair, and he enrolled her in his trial testing nivolumab and ipilimumab. “He told me everything would be all right,” Schlegel said. “I believed him.”

Her treatment began with gamma knife brain surgery, which was followed by immunotherapy. She went to LVH-Cedar Crest for infusions every other week or so. Each visit was an all-day affair. She watched the drugs slowly drain from an IV bag, entering her body through a port on her chest. Briefly, her blood sugar spiked. But the vomiting, malaise and hair loss of chemotherapy or radiation — she didn’t experience anything like that.


Even Nair, the eternal optimist, could hardly believe Schlegel’s response. “Never in my career have I seen that amount of spread — liver, lungs, brain — become cancer-free,” he said.

Nair co-wrote an article about the trial, published last month in The Lancet Oncology. It says that treating melanoma patients with nivolumab up front, either with ipilimumab concurrently or sequentially, nearly doubles the three-year rate of survival, to 65 percent. Essentially, nivolumab allows the immune system to “see” cancer cells, which then allows it, after ipilimumab has released its brakes, to attack full-throttle — and destroy the cells. The FDA approved this approach late last year, long after Schlegel began her treatment.

Generally, cancer patients must be cancer-free for five years before they are said to be cured. Schlegel has two more years to go. With every routine checkup, she gets that much closer.

“Every time she gets a scan, I get palpitations,” Nair said.

skennedy@mcall.com
610-820-6130