Men with advanced prostate cancer may be able to take one fourth the standard dose of abiraterone acetate (Xytiga, Janssen) in conjunction with a low-fat breakfast, and the drug's efficacy will still be comparable to the efficacy of the standard dose when the drug is taken on an empty stomach, as recommended, according to findings from the first randomized trial on the subject.
As a result of the dose reduction, the drug is 75% less expensive — a boon for anyone hampered by prohibitive copays, said lead author Russell Szmulewitz, MD, from the University of Chicago, in Illinois.
Patients taking abiraterone typically stay on the medication for 12 to 18 months, so the savings with the reduced dose would be significant.
He said that the retail cost of abiraterone is about $9000 a month. In a common scenario, patients with Medicare part D with a prescription drug plan typically have a copay of $1000 to $2000 a month.
"Sometimes, patients will say, 'I can afford this three or four times a year, but not every month,' " Dr Szmulewitz told Medscape Medical News here at the Genitourinary Cancers Symposium (GUCS) 2017, where he presented the study results.
He also said that it is well known that abiraterone is more efficiently absorbed with food. However, abiraterone, like many cancer drugs, was tested at fasting levels in clinical trials. "In cancer, there's a belief that fasting will give you better and more predictable drug levels with patients," he said.
Other experts at the meeting sounded notes of enthusiasm about the results when asked for comment by Medscape Medical News.
Elizabeth R. Plimack, MD, of the Fox Chase Cancer Center, Temple Health, in Philadelphia, Pennsylvania, said she would suggest the lower-dose strategy to patients who cannot afford the drug. "It is well documented that lower doses [of arbiraterone] with food can be effective," she said.
Matthew Cooperberg, MD, of the University of California, San Francisco, said that the results are "important information for real-world practice, in which some men cannot afford the copays and either don't fill the prescriptions or deliberately skip/reduce doses in order to stretch out each refill."
But Dr Cooperberg also said he would like to see the paper published rather than just presented as an abstract. "It's worth considering. Hopefully, larger trials will follow," he added.
Small, retrospective studies have also investigated single-pill dosing in prostate cancer patients in comparison with the standard four-pill dosing with fasting and have evaluated a variety of measures, said Dr Szmulewitz.
However, the new prospective, multicenter, international phase 2 trial is unique ― 36 patients were randomly allocated to receive 250 mg of the drug with a low-fat breakfast, and 36 patients were randomly assigned to receive the standard dose of 1000 mg on an empty stomach.
In the study, prostate-specific antigen (PSA) level, which was the primary outcome, was assessed monthly. The mean log-change in PSA level at 3 months was nominally greater in the 250-mg arm (-1.59 vs -1.19). Thus, the data established the noninferiority of the lower-dose-with-food approach. Median time to PSA progression was about 14 months in both arms (P = .53).
Preliminary analysis of pharmacokinetics (PK) showed no difference in the peak serum concentration beyond the first cycle, with lower PK variability in the 250-mg arm.
Patients who took the drug with food appeared to have an additional benefit: they were less likely to complain about stomach discomfort than those who took the drug as recommended.
The men in the study were aged 52 to 89 years (median, 74 years). They had advanced prostate cancer and had experienced disease progression despite standard initial hormonal therapy.
According to a press statement, with many oral drugs, including abiraterone, there is a "food effect," which can alter how the drug is absorbed. Blood levels of the drug can be up to 17 times higher when the drug is taken with a high-fat meal, and it can be four to seven times higher with a low-fat meal. Low-fat meals would include breakfast items such as cereal, low-fat milk, and eggs. Foods to be avoided with the 250-mg dose of abiraterone include fatty meats, such as sausage and bacon, Dr Szmulewitz said.
The study has limitations, he commented.
"I don't think this can globally change practice," he said, explaining that PSA response and progression are not "bona fide" clinical endpoints.
"It opens a window for conversation with patients and providers. If there are cost issues or GI tolerability issues (on a fasting state), this gives some confidence on an alternative way to take the drug," he continued.
Dr Cooperberg also commented on limitations. "The small study size and short follow-up are real concerns," he said.
Nonetheless, he concluded: "This is an important, pragmatic study in an era of skyrocketing pharmaceutical costs."
Dr Szmulewitz, Dr Cooperberg, and Dr Plimack have disclosed no relevant financial relationships.
Genitourinary Cancers Symposium (GUCS) 2017. Abstract 176, presented February 16.
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου