This detailed news release from the University of Pennsylvania describes results of a literature review of small clinical trials that suggest far broader treatment possibilities for a type of cell-cycle or checkpoint inhibitor drug already approved by the FDA for its effectiveness against a form of hormone-dependent breast cancer. The drug, palbociclib, interferes with the hallmark rapid division of cancer cells by inhibiting two so-called cyclin-dependent kinases (or CDKs), the enzymes CDK4 and CDK6, which ramp up cell proliferation and are widely present in a variety of malignant tumors. These cell cycle saboteurs are the hot new focus of individualized cancer treatments because of their relatively non-toxic side effects and — alone and in combination with other drugs — their ability to extend progression-free survival. The release does a good job of noting the rapid emergence and track record of palbociclib, which is taken usually once a day by mouth, and its potential use in lymphoma, other forms of breast cancer, sarcomas and teratomas. The release would have been made stronger if it had included more information about the type of breast cancer palbociclib was approved for by the FDA (hormone receptor positive tumors), and about costs, along with more data about prevalence of the cancers it already treats and may have the potential to treat. We also think the release gets ahead of itself when talking in unqualified terms about the drug’s “potentially broad applicability” and “real promise for addressing a variety of cancers.” Those applications may pan out and then again they may not; the release only seems to consider the first possibility.
To say that CDK and other checkpoint inhibitors are exciting oncologists and their patients alike is an understatement. The U.S. Food and Drug Administration is fast-tracking new ones and existing ones for additional uses, and drug makers already are pouring extraordinary resources into marketing them. To be sure, these drugs — as the Penn release points out — are not cure-alls, do carry side effects, and still seem in many cases to work best only when combined with radiation and other drug therapies. And — as the release fails to point out — they are mega-expensive. Cancer patients and their families are right to be hopeful about the value of palbociclib and other cell cycle therapies. But the hope is that news releases and news stories will also underscore the clinical limitations and accessibility issues that accompany these new treatments.
The release goes to some lengths in describing the quantitative and qualitative benefits of pairing palbociclib with other anti-cancer drugs, but offers not a word about costs. In this case, costs are significant. Pfizer has pegged palbociclib at $9,850 per month. Carrying an informal calculation forward puts the cost of the drug at about $40,000 per prolongation of survival for four months. The consequences of such pricing remain unclear owing to subsidies and discounts. But for many patients the costs are not covered by insurance and drugs may not be accessible to all who need them. They also put a major strain on the entire health care system.
The release claims that the drug offers lower toxicity than other drugs, ease of use, and effectiveness as either an add-on or stand alone treatment but with very little data backing up the claims. The release summarizes the outcomes of two small trials using palbociclib in somewhat muddy terms. In one involving 17 previously treated mantel-cell lymphoma patients, the drug is attributed to one “complete” response and “two partial responses.” Another trial with 29 sarcoma patients treated with palbociclib showed “progression-free survival of 66 percent at 12 weeks.”
The release might have added more specifics about the impact and meaning of “complete” and “partial” responses as well as extended “progression-free survival” with hard data that would help readers compare such survival with and without the use of the drug.
The release notes the drug’s side effects, including the most common one which renders patients more susceptible to infections. However, it needs to be pointed out that the studies involved very small numbers of patients and the emergence of more serious side effects may not be seen until the drug is observed in a larger population.
We rated this Not Satisfactory because the studies highlighted were Phase 2 trials without controls or any information about the adequacy of blinding in observers of the outcomes. When “progression-free” outcomes are used, there is a certain amount of subjectivity that is part of the measurement, which could make the results invalid. By focusing mostly on the molecular biology the news release obscures the quality and results of any clinical studies that have been done.
The release describes the unpublished, short-term results of two small clinical trials, but omits specific information about the investigators’ other ongoing trials, and gives no information about the protocol used to select the 130 “relevant” articles in the published literature, or how, exactly, those data added evidence for broader use of the drug beyond breast cancer.
There seem to be some patients who get more benefit than others suggesting that there may be individual cellular markers that may predict response.
No disease mongering here.
In fact, we wish the release had given some attention to the prevalence of the specific tumors studied as well as the types of tumors the drug is intended to target.
The release notes that Pfizer and the National Institutes of Health funded the review.
Since there is no comparison to standard therapy it’s hard for the reader to come away knowing what the pros and cons are for the drug and how advantageous a tumor cell inhibitor might be to a patient’s specific cancer.
There’s no mention of whether this drug is currently approved or how widely this drug is used.
The drug is the first of a new class of drugs and that’s noted in the release.
While the language used is professional in tone it includes some overly optimistic statements such as “potentially broad applicability” and “real promise for addressing a variety of cancers” which suggests the drug sponsors are angling for future applications beyond those that have been studied. It is too early in the process of studying the drug to be so optimistic about treatment success — at least not without providing some tempering language to balance expectations.