A group of prominent cancer doctors is planning a novel assault on high drug costs, using clinical trials to show that many oncology medications could be taken at lower doses or for shorter periods without hurting their effectiveness.
As Exhibit A, they point to their pilot study involving a widely prescribed drug for advanced prostate cancer. Cutting the standard dose of Zytiga by three-quarters was as effective as taking the full amount — as long as patients swallowed the medication with a low-fat breakfast rather than on an empty stomach, as directed by the label.
“It's inefficient, even wasteful, to take this medicine while fasting,” University of Chicago oncologist Russell Szmulewitz said in presenting the data at a conference earlier this year. Reducing the dosage of the $9,400-a-month medication as studied would sharply lower costs even for well-insured patients, he said. Another benefit would be fewer side effects; the patients who'd eaten breakfast with Zytiga, for example, had fewer stomach issues.
Szmulewitz and others now want to run full trials to see whether the doses of other oral oncology drugs can be ratcheted back because of the “food effect,” which can alter how a medication is absorbed. They also plan to explore whether the duration of some prescriptions can be shortened and whether some cheaper non-cancer drugs can be substituted for expensive cancer ones. They recently created a nonprofit organization, the Value in Cancer Care consortium, to organize their work.
The initiative is the latest response to rising concerns over “financial toxicity,” the economic devastation that can be wrought by the high cost of cancer care. With new oncology therapies routinely debuting at more than $100,000 a year, “lots of people are worried about developing drugs that people can't get,” said Leonard Saltz of Memorial Sloan Kettering Cancer Center in New York, who helped organize the new group. The effort is also an acknowledgment that, despite President Trump's grousing about high drug prices earlier this year, they're unlikely to change soon.
“This is the most practical and realistic way we have available right now to reduce the cost of cancer therapy and to increase value,” said consortium chairman Allen Lichter, a former president of the American Society of Clinical Oncology. “It doesn’t require Congress to do anything or regulators to approve imports. It involves careful clinical study to show the oncology community some of these drugs can be used better. This is a win-win situation if we can show it works — fewer side effects and much better access for our patients.”
Lichter and others pitched their idea to dozens of colleagues in a closed-door meeting last weekend at ASCO's annual conference in Chicago. Their next challenges are raising money — they estimate each 300-person trial will cost $3 million to $5 million — and setting up a network of medical centers to run the trials.
Mark Ratain, a pharmacologist who directs the University of Chicago's Center for Personalized Therapeutics, said he's optimistic that the group can raise money from philanthropists, insurers and even some government health systems like Britain's, given that the result could be big savings. An initial $1 million grant already came from the Laura and John Arnold Foundation in Houston.
The doctors' initial study with Zytiga illustrates their thinking. The randomized trial enrolled 72 prostate-cancer patients, with half taking the recommended standard dose of 1,000 milligrams on an empty stomach and the other half taking 250 milligrams with a low-fat breakfast, such as cereal with skim milk.
Despite the big difference in dosages, there was no difference in the drug's activity, as measured by prostate-specific-antigen levels in each group. In addition, the length of time before the disease worsened was the same for both groups, about 14 months. The oncologists intend to repeat the study with many more patients.
Ratain said food can increase or decrease the absorption rate, or bioavailability, of some drugs. Zytiga has an especially large “food effect”; taking it with a low-fat meal can increase its level in the blood by four to seven times. But many oral cancer drugs, including Zytiga, stipulate that patients should fast because that's how they were tested.
Zytiga's manufacturer is not convinced by the pilot study, warning against taking a lower dose with food. “Use of food as a way to increase bioavailability in patients with cancer could present problems and risks,” the drug's manufacturer, Janssen, said in a statement. “Given the variation in the content and composition of meals, the recommendation is to take Zytiga exactly as described in the prescribing information.”
Some doctors also dislike the idea of changing the way drugs are administered for cost reasons. Benjamin Davies, an assistant professor of urology at the University of Pittsburgh School of Medicine, said he thinks many cancer drugs are too expensive. But cutting back on their dosage “seems like a backwards approach,” he said. “We should address drug prices directly. To suggest that we can't regulate or legislate our way out of this problem is a wrong assumption.”
Physician and economist Scott Ramsey of the Fred Hutchinson Cancer Research Center in Seattle, who is serving on the consortium's advisory board, disagrees. He supports clinical trials to explore using cancer treatments in more efficient ways. “We desperately need to find ways to reduce our cancer-spending trend,” he said.
Zytiga, also called abiraterone, is a particular case in point. New research presented at the conference showed the drug could benefit many more men with advanced prostate cancer, which means annual spending on the drug could surge, Davies wrote in Forbes.
Saltz said the group also wants to test whether some non-cancer drugs that show anti-tumor activity could be used as cheaper substitutes for expensive oncology therapies. For example, an inexpensive immunosuppressant called Rapamune, or sirolimus, has many similarities to an expensive medication called Afinitor, which is used for breast and kidney cancers. “There is a reasonable expectation that sirolimus would be functionally very similar,” Saltz said.
The key, Lichter told the trade publication the Cancer Letter, is in running trials to gather the data. “As a patient, I'd want to know that I can safely take this lower dose and not sacrifice any of the benefits.”