The Irresponsible ‘Killing Cancer’ Talk
Framing every scientific advancement in the cancer world as a “miracle cure” may attract readers, but the false hope it promotes does a disservice to patients.
If you give the media a cancer study, they’re going to want a miracle cure to go with it.
This month, Chicago hosted the annual meeting of the American Society of Clinical Oncology (ASCO), one of the largest events in the cancer treatment community. Over 30,000 professionals attended hundreds of scientific and educational sessions. ASCO is the premiere venue for presentation of the most rigorous investigations of the most potential cancer therapies. The most promising drugs will be presented to the press.
Next week, my patients are more likely to ask me about the recent articles on “Cuban cancer vaccine” or about the cancer-attacking poliovirus being trialed at Duke University and featured on 60 Minutes. Unlike the practice-changing data from the PALOMA3 trial for patients with metastatic breast cancer, neither was presented at ASCO this year but they’ve certainly had good press.
Both are worthy of interest, but not for the reasons screamed in the headlines.
Lets begin with the polio vaccine trial, currently being studied in the treatment of a brain tumor called glioblastoma (GBM). GBM is a scourge. It is an aggressive tumor that originates in the brain (as opposed to spreading from another organ such as the lung) and carries a dire prognosis.
The brain is obviously precious biologic real estate. It’s not forgiving of a progressively infiltrating tumor. And the organ can only tolerate so much before the side effects of treatment start to mimic destruction from the disease. After diagnosis of a GBM, Senator Ted Kennedy, with every resource at his disposal, survived 15 months, the statistical average for patients diagnosed with this disease.
In this context, 60 Minutes produced their story Killing Cancer after a 10-month period of observing a Phase I trial of modified poliovirus as a novel GBM therapy. Phase I trials are where new potential therapies start their clinical life. Untested in patients, the goal of a Phase I trial is, by definition, to find the maximum safe deliverable dose, not to measure a drug’s efficacy.
Due to the obviously precarious nature of giving an untried therapy to everyday patients, Phase I trials are typically reserved for those who don’t qualify for standard therapies and have few to no options left. The rigorous patient selection is a mechanism designed to protect trusting, frightened, and desperate patients from the best intentions of doctors who may have more faith in a new drug than experience with it.
In Killing Cancer, viewers are introduced to four of the study subjects and the research team involved in their care. We learn that when genetically re-engineered from a paralysis-inducing disease, the polio virus can used both as a vector to specifically infect tumor cells, and stimulate a directed immune response against only those cells.
The Duke medical team elegantly describes the mechanism and their experience with the drug using cautious tones and measured excitement. The tone of correspondent Scott Pelley’s narrative, however, is considerably less guarded. “Some of the patients [in the study] use words that doctors don’t use, like ‘miracle’ and ‘cure.’” Unfortunately, so does Pelley. One can visibly observe members of Duke team struggle to reframe dramatically phrased questions. It’s an uphill fight.
The patient stories showcased are affecting.
The first enrollee in the study is a young nurse trainee who is able return to school, graduate, and bring her own experiences to bear in her healthcare career. At the time of production, she is three years out from the trial treatment, in remission, and vibrant. We watch her meet a retired physician—the second enrollee—who had written his own obituary before going into remission after taking the poliovirus. For a trial not designed to show a response, these testimonials prove powerful stuff.
And in the face of this emotional power, and Pelley’s dramatic telling of the impassioned work behind getting these patients as far as they’ve come, the story of those who did not survive—50 percent so far—simply can’t make the impact it should. That’s a shame because couched in proper perspective, this trial is still amazing stuff.
Pelley takes pains to suggest that the deaths may be from the dose escalation rather than from tumor. Maybe. Is this drug revolutionary, a potential cure for some? Is it evolutionary—not a cure but extends survival? Or are we just seeing some favorable responses in a proof-of-concept study that won’t translate into something meaningful for most patients. We simply don’t know.
For a variety of reasons, patients enrolled in Phase I trials often do better than average. The very nature of a Phase I study means that we aren’t in a position to assess the drug’s efficacy. That doesn’t stop 60 Minutes from trying.
Facts are also a problem for the story.
“Radiation flashed on in the 19th century,” we are told by the narrator. “Chemotherapy began to drip in the 20th.” This, Pelley announces, is a 21st century discovery: a “big leap forward: awakening the power of the body’s immune system.”
The patients had “no options other than what’s never been tried before.” The setup here is misleading because the concept of immune-modulating drugs and cancer-targeting viruses are hardly new. In fact, they’ve been studied for decades, and have long been established in clinical use.
Bacillus Calmette-Guerin immunotherapy (BCG) was first used against cancer in the 1930s. IT was studied against early stage bladder cancer in 1976. It was effective then, and is still in use. Half a decade ago, two practice-altering studies using vaccine therapy and immuno-modulation for prostate cancer and melanoma were published in the New England Journal of Medicine.
These were not early-phase dose escalation trials but Phase III studies providing the highest level of evidence that the study drug was superior to the previously established gold standard. Currently, 23 vaccine trials are open for GBM. Actually, so great is the momentum for immunotherapy in cancer care right now that one of the leading educational sessions at ASCO this year was a primer entitled “The ABC’s of Cancer Immunotherapy.”
In spite of how its framed in the 60 Minutes piece, the truth is that to be a competent oncologist in the 21st century is already to be well-versed in the field of immunomodulation. There’s nothing revolutionary about it.
This leads us to the Cuba’s much-heralding CIMA-vax trial. CIMA-Vax is a vaccine designed to raise antibodies against epidermal growth factor (EGF). The receptor for EGF is expressed on many cancers. The theory is that by stimulating the immune system to reduce EGF in the body, cancers will be starved of a molecule that feeds them. “Cuba’s had a lung cancer vaccine for years, and now it’s coming to the U.S.,” the Huffington Post and Wired both reported in May.
And CIMA-vax does work. In 2008, a well-designed trial demonstrating efficacy was published in a high-impact medical journal and a follow-up study was presented at ASCO 2013, though both to little fan-fare. So why the sudden interest?
The sensationalized headline was clearly the consequence from the Obama administration’s recent easing of the Cold War-era U.S. trade embargo on Cuba. Gov. Andrew Cuomo came back from his mission to Havana with drug figuratively in hand. New York’s Roswell Park Cancer Institute in Buffalo will start the first clinical trials of CINA-vax in the U.S.
Wired accurately notes that the drug won’t be a “game changer,” nor likely even practice changing. “People with lung cancer already have treatment options with the same [mechanistic] goal.” In other words, as it stands in 2015, CIMA-vax is essentially a “me too drug” that works along the same lines as several others already in use in the U.S.
Now there is a story here. Researchers hope to study the potential of CIMA-vax as a preventative intervention in selected patients, to be used much the same way the human papilloma virus (HPV) vaccine is used to protect against cervical and other HPV-positive cancers. Such research was impossible in financially strapped Cuba but quite feasible in the U.S. And the bigger picture is the value of the cross-pollination that occurs when we cooperate with other nations on the medical front.
So it’s not that the poliovirus and CIMA-vax aren’t worthy of medical study, or that these early trials aren’t worth media coverage. Both are interesting and exciting in concept. But the breathless enthusiasm and selective framing of the story is guaranteed to lead to unrealistic expectations on the part of cancer patients. That’s not hope, that’s a disservice.
60 Minutes invested 10 months in researching their segment on the polio vaccine—evidently, not enough time to get the framing right. Indeed the news magazine neglected to mention their long standing interest in Duke’s brain tumor research: In 2002 Ed Bradley reported on the teams work in monoclonal antibodies against GBMs, branding that exciting development a “smart bomb.”
One wonders how the recent story would have looked if they had showcased the more than 100 phase I trials currently open for GBM.
It’s hard to resist a “win” when a patient beats the odds with an exciting new trial drug. As a doctor in practice for 11 years, I certainly know the feeling first hand. But I also know about the caution in overstating an early success.
I recently recalled to my trainees the excitement when we first gave bevacizumab (also called Avastin) to a patient with a recurrent GBM. Within days her weakened right side came back and her follow-up MRI showed the tumor had “melted away,” to use the jargon of conventional reportage. We had never seen that before.
Early trials showed the same thing. The definitive trials for the drug resulted in 2014 and showed no survival benefit for patients routinely receiving bevacizumab in the treatment of GBM. There was even a suggestion of a worse quality of life in some. The explanation for this is beyond the scope of this article, but the lesson for caution is clear.
Hope is enormously important for patients. I learned from a mentor never to give my patients survival data unless they repeatedly ask for hard numbers. No matter what your intentions, coming from your lips, a number too often feels too much like a verdict. “My doctor gave me six months.” No she didn’t, but it certainly feels that way.
Every patient deserves to be treated with the fullness of our expertise and as if they will be like my patient who six years on from his diagnosis of a GBM, invited me to his 80th birthday party and told me over a glass of wine, “You don’t need to be my doctor any more.”
But oversold headlines and correspondents who try to cajole a physician’s response to early results of a Phase I studies as miraculous are a huge disservice to patients.