There’s a trope in medicine that doctors only have three ways of dealing with cancer: cutting (surgery), burning (radiation), and poisoning (chemotherapy). Oncologists have long sought a fourth path—using the body’s own immune system to attack tumors—but progress has been very, very slow.
Thus, it was surprising to see a headline in the Pittsburgh Post-Gazette last Wednesday that read, “Cancer vaccines may be on the verge of wider use.”
My first thought was, what kind of vaccines are we talking about? My second was, well, if we’re talking about vaccines for treating cancer (as opposed to preventing it), one would be a start.
Lately, there has been a lot of chatter that, by May 1, the U.S. Food and Drug Administration is expected to approve Provenge (sipuleucel-T), a drug for the treatment of metastatic prostate cancer. It would be the first vaccine approved in the United States for the treatment of cancer, and, as such, an important step toward enlisting the immune system’s natural defenses in the fight against a disease that kills over half a million Americans each year.
But don’t expect to find much enlightenment in the Post-Gazette’s article. The piece, by staff writer Mark Roth, gets off to a bad start by reporting that, according to scientists, “we may be on the verge of being able to vaccinate people against cancer in the same way we do with infectious diseases … The first commercial cancer vaccine out of the gate is likely to be sipuleucel-T, a vaccine against prostate cancer being made by Dendreon Corp. of Seattle, Wash.”
This is a bad start for many reasons. First, Roth makes no distinction between vaccines designed to prevent cancer and vaccines designed to treat cancer. The expression “vaccinate against” implies that he is writing about the former, but Provenge is designed to treat cancer, as are most of the other vaccines cited in the article. Thus, sipuleucel-T does not “vaccinate against” prostate cancer, but rather creates an immune response to fight cancer cells that are already present. Moreover, even prevention drugs don’t “vaccinate against cancer,” strictly speaking—they vaccinate against viruses that can cause cancer.
That brings us to the second problem with Roth’s article. “The first commercial cancer vaccine” is already out of the gate and has been for some time. It is a preventative vaccine against the hepatitis B virus (HBV), which can cause liver cancer. The FDA approved it in 1981. There is also Gardasil, a vaccine against two strains of human papillomavirus that can cause cervical cancer, which the FDA approved in 2006. In 2008, the FDA approved Gardasil for use in preventing HPV-associated vulvar and vaginal cancers as well.
According to a useful cancer vaccines fact sheet from the National Cancer Institute, “many scientists believe that microbes cause or contribute to between 15 percent and 25 percent of all cancer diagnosed worldwide each year, with the percentages being lower in developed countries than in developing countries.” But in any story about preventive vaccines, it is important to note that in addition to HBV and HPV, only three other viruses, one bacterium, and two parasites have even been associated with certain types of cancer.
There are currently no vaccines approved in U.S. for the treatment of cancer, and therein lies the third problem with Roth’s article. Even if the FDA gives Provenge the green light this spring, it will likely be awhile before it is fair to say that cancer vaccines are “on the verge of wider use.” Even Cure magazine, which is owned by U.S. Oncology, Inc. (a network whose goal is “to increase patient access to, and advance the delivery of, high quality cancer care in America through our clinical insight and expertise”), recently reported that “cancer vaccine researchers caution that it could be years before clinicians routinely use this immunological approach to treat cancer.”
For the last three years, Provenge itself has been the source of intense feuding between the FDA on the one side, and Dendreon investors and cancer patients on the other. An FDA advisory committee recommended approval of the vaccine in 2007 after a clinical trial had found that men who received Provenge lived about four months longer, on average, than those who received a placebo. But the agency balked at the recommendation and rejected Provenge, saying more data was needed.
In April 2009, Dendreon released the results of a larger trial, which supported the survival gains demonstrated in the first study. Those results are a positive sign, to be sure, but American Cancer Society Chief Medical Officer Otis W. Brawley told the WebMD news site that closer scrutiny of the trial was still needed. So approval of the drug by or before May 1 is anything but certain.
Roth’s article for the Post-Gazette does not dwell on Provenge, however. After introducing the prostate cancer drug at the top of the story, Roth immediately goes on to write, “Not far behind in the [approval] pipeline is Stimuvax, a vaccine being made by Merck in Germany that targets a cancer marker known as MUC1, which is present in many different tumors.” But it is not until twenty-one paragraphs and much digression later that he gets around to mentioning that, “the current testing has been suspended temporarily because one patient got encephalitis.” And Roth quickly dismisses that not insignificant concern with the declaration that, “the man whose company invented the vaccine is [nonetheless] encouraged by the progress it is has made.”
At any rate, Stimuvax and Provenge aren’t really the point of Roth’s story, and he uses them mainly to segue into local research by Dr. Olivera Finn at the University of Pittsburgh Medical Center (UPMC). Finn has developed a cancer treatment vaccine that also targets the MUC1 marker, but Roth provides almost no additional detail except to say that it has “been in development for several years [and] has shown limited success in advanced pancreatic cancer patients.”
It’s a shame that Roth’s reporting isn’t better, because he seems to be onto a perfectly decent story. In an interesting twist, Finn tells him that she believes her vaccine will work best in people who do not have cancer, so they’re now giving it patients who have precancerous polyps in their colons, to see if it prevents the onset of colorectal cancer. Alas, the only thing else Roth has to contribute is that Finn is “still a couple years away from being able to report results.”
He quickly moves on to another piece of UPMC research into a vaccine to treat gliomas, a type of brain tumor. Roth finally begins to provide some details here, reporting, “The trail will be small to start with, involving 18 patients with new cancers and nine with recurrent tumors.” He also explains how the vaccine is used with an adjuvant called Hiltonol that boosts the body’s immune response. The reader has no idea when the trial will begin, however. More importantly, the very early-stage research does nothing to support the article’s premise that “cancer vaccines may be on the verge of wider use.”
According to the National Cancer Institute’s searchable online database, there are currently sixty-nine Phase 3 clinical trials (the last phase of testing required before applying to the FDA for new drug approval) for cancer treatment vaccines happening in the United States. That doesn’t mean all of them will lead to the filing of an application, let alone new drugs, but if a reporter wants to assess progress in the field, the database is the place to start.
In an article for The Saturday Evening Post last August, Sharon Begley reported on “three large-scale studies, called Phase III clinical trials, presented at the 2009 meeting of the American Society of Clinical Oncology (ASCO), [which] suggest that cancer vaccines may one day play a role in cancer treatment.” Begley provides plenty of detail on the methods, size, and results of each one, explaining why they may be considered “notable successes.” Yet she cautions against expecting that the research will “open the floodgates for cancer vaccines,” which have seen many, many failures.
In February 2009, an excellent piece in Nature Biotechnology, with reams of supplementary tables and charts, reported that, “To date, an estimated 7,000 people have participated in late-stage clinical trials of active cancer immunotherapies. These have largely been an exercise in frustration, as candidates—including a few that looked quite good in early trials—have fallen by the wayside in pivotal phase 3 trials.”
None of this is to say that cancer vaccines (both the preventive and treatment varieties) don’t deserve more coverage. The approval of Provenge would indeed be a significant step for oncology in the Untied States, and journalists should use it to pitch stories exploring the field. The reporting, however, should display far more caution and judiciousness than found in the Post-Gazette.
[Correction: This story was changed to reflect that Dr. Finn works at the University of Pittsburgh Medical Center, not the University of Pennsylvania Medical Center.]