The story paraphrases sources saying the approval of Xalkori (Pfizer’s brand name for a pill containing crizotinib) “proves the value of precisely targeting rare diseases linked to gene variants.” It is not clear if that phrase refers to the value for patients or company shareholders, because the next paragraph says this drug “epitomizes drugmakers’ new strategy of developing very expensive but effective medicines for relatively few patients to replace the blockbusters for the masses now getting competition from generic drugs.”
This story would have been better if it had focused on how the FDA has decided to offer some novel combinations of tumor gene tests and therapies to selected patients based on suggestive results from small, preliminary trials, and then requiring applicants to complete conventional randomized controlled trials in order to keep the drug on the
market. It should also have given readers some of the context available in documents posted online by the FDA, Pfizer and other sources about the state of the science regarding this drug.
On the plus side, the story makes clear that this drug is meant for a small and very specific group of patients. It also is clear about the high cost of the therapy.
People with often-deadly diseases such as advanced lung cancer are hungry for new treatments. Journalists have a responsibility to put preliminary suggestions of progress toward new treatments in the proper context. In this case, the story should have been more clear about tentative nature of the evidence supporting use of a new drug in certain patients and that continued use all depends on the results of trials that are still underway.
The story clearly states near the top that this treatment is “very expensive.” It reports that crizotinib treatment costs about $9,600 per month and that patients may continue to be treated until the cancer resumes spreading. There is also a reference to an assistance plan offered by Pfizer. The story also reports that tumors “shrank or stopped growing in just over half of patients for nearly two years on average.” From this information, careful readers could calculate that the drug cost (not including associated medical care and tests) would routinely approach a quarter of a million dollars per patient. It would have been helpful if the story had provided this calculation. The story also reports that the test needed to identify appropriate patients costs $250.
Readers of this story are likely to get an exaggerated sense of the benefits of this drug. As noted above, the preliminary trials completed so far did not produce evidence of improved outcomes or survival, nor did those trials include any comparison of the new treatment with existing alternatives. The story reports that “tumors disappeared, shrank or stopped growing in just over half of patients for nearly two years on average.” The drug label indicates that tumors “disappeared” in only three patients out of 255. The story reports on two patients who gave glowing reports of their responses, but there were no quotes from more typical patients who had limited, if any, responses or who endured serious side effects. The story then includes a reference to the short survival of typical lung cancer patients, without included the necessary caveat about the unreliability of such historical comparisons.
The one-sided reporting provides an unbalanced view of the drug’s potential benefits. The story should have been clearer that the main reason this drug received conditional approval is that there is a reasonable likelihood of benefit; and that we won’t know if that benefit is real until the ongoing trials are completed.
The story quotes sources claiming “You’re going to be sparing individuals side effects” and it describes Xalkori as “a pill with relatively minor side effects compared to the hair loss and nausea that chemotherapy can cause”. The drug label and FDA news release are less dismissive of the problems experienced by patients in the preliminary trials so far.
While few trial participants reported symptoms severe enough to cause serious harm, hospitalization or symptoms so bad they couldn’t carry on routine activities, most of the patients did report problems with vision and more than half reported nausea, diarrhea, vomiting or other gastrointestinal symptoms, including some that may have required treatment. Treatment was interrupted in 36 percent of the patients in one of the trials and 45 percent of the patients in the other trial. Five percent of patients had neutropenia, abnormally low white blood cell counts. (See http://labeling.pfizer.com/showlabeling.aspx?id=676)
The FDA news release included a list of side effects and warned of potentially life-threatening reactions. “The most common side effects reported in patients receiving Xalkori included vision disorders, nausea, diarrhea, vomiting, swelling (edema), and constipation. Vision disorders included visual impairment, flashes of light, blurred vision, floaters, double vision, sensitivity to light, and visual field defects. Xalkori use has also been associated with inflammation of the lung tissue (pneumonitis), which can be life-threatening. Patients with treatment-related pneumonitis should permanently stop treatment with Xalkori. The drug should not be used in pregnant women.” (See http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm269856.htm)
The story should have summarized these side effects and warnings. It should have also noted that since the trials reported by Pfizer included only 255 patients, little is known about the potential risk of rare, but serious, side effects.
If only this story had been as straightforward as the drug label that starkly declares, “There are no data available demonstrating improvement in patient reported outcomes or survival with XALKORI.”
(See http://labeling.pfizer.com/showlabeling.aspx?id=676) Instead, the story offers a murky statement that, “Research to determine overall survival is ongoing.”
Deep in the story, readers are told that this drug approval is unusual because standard trials to compare the new treatment to conventional care have not been completed. However, the story does not report that only 255 patients were included in the trials. Readers are left to figure out on their own that there was no blinding or randomization done in the completed trials.
The FDA news release offers information about the tentative nature of the evidence and an explanation that the drug was approved before convincing evidence of benefit was available only because these patients don’t have good treatment alternatives. (See http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm269856.htm) The story should have included this important context.
The top of the story notes that this drug is intended for use in a small subset of lung cancer patients. Deeper in the story, readers are told that roughly 4 percent of patients with advanced non-small cell lung cancer have tumors with the gene variant that may respond to this drug, and it quotes a Pfizer company source as saying that about 6,000 Americans a year develop cancer fitting this definition. It would have been helpful for this story to include some estimate of the number of lung cancer patients who may be candidates for testing to see if their tumors have the relevant gene.
While the story notes the conflicts of some sources, it appears that all the experts quoted were participants in a conference call arranged by Pfizer.
The story appears to imply that standard treatments don’t work for patients with tumors that have this specific gene variant. However, cancer treatment statistics indicate that these patients are just as likely as other patients to respond to first-line treatment. The new drug is intended to be used when those standard treatments aren’t enough. Then the tumor gene test is needed, because giving this new drug does not appear to do any good for the overwhelming majority of patients, it is to be used only in that subset of patients with tumors that might be susceptible. Also, the story should have been clearer about explaining that neither of the preliminary trials included any comparison to standard treatment.
The story is clear that crizotinib recently received FDA approval for use “along with a companion diagnostic test for just a small subset of lung cancer patients.” However, while the story refers to ongoing research, the actual status of the drug is not explained. The FDA approval letter warns that, “If postmarketing trials fail to verify that clinical benefit is conferred by XALKORI (crizotinib) Capsules, 200 mg and 250 mg, or are not conducted with due diligence, we may, following a hearing in accordance with 21 CFR 314.530(b), withdraw or modify approval.”
Readers should have been clearly told that this drug is still very much on trial.
Based on this story, readers may believe that this drug is the first of its kind. However, the FDA news release says the gene test is the truly novel part of the combination approved and the release goes on to point out, “It is the second such targeted therapy approved by the FDA this year.” Nevertheless, the approach taken with this sort of gene test and specfic drug combination is new and very different from typical chemotherapy, which is the angle highlighted in the story.
This story appears to rely entirely on a conference call arranged and managed by Pfizer, in essence an audio news release.
Systematic, Criteria-Driven
The tale of two “negative” studies. Or, how spin is applied to make research findings look more impressive. A must read. https://johnmandrola.substack.com/p/the-tale-of-two-negative-studies
The @nytimes chose to interview one of the editors of the @AnnalsofIM (publisher of this paper) who "gushed with extraordinary glee: It’s huge! There are very few things that reduce your mortality by 30%."
Turns out coffee is not one of those few things despite all that glee. https://twitter.com/garyschwitzer/status/1533202075928215558
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