NOTE TO READERS: When this project lost substantial funding at the end of 2018, I lost the ability to continue publishing criteria-driven news story reviews and PR news release reviews - once the bread-and-butter of the site going back to 2006. The 3,200 archived reviews, while still educational, are getting old and difficult for me to technically maintain on the back end of the website. So I am announcing that I plan to remove these reviews from the site by April 1, 2021. The blog and the toolkit - two of the most popular features on the site - will remain. If you wish to peruse the reviews before they disappear, please do so by the end of March 2021. After that date you may still be able to access them via the Internet Archive Wayback Machine - https://archive.org/web/.
Read Original Release

Release omits key safety findings of breast cancer drug combo study

Drug combination slows breast cancer spread

Our Review Summary

capsulesThis news release describes findings from a study published in Lancet Oncology that found that a combination of drugs slowed cancer progression an average of nine months in women with HER2-negative breast cancer, the most common type of breast cancer. The release provides data on the drug combo’s effect on time to progression, which may be a clinically important measure. But women also want to know if it will help them live longer, and this news release doesn’t address that. The release has some strong points, including clear reporting and useful information on how the drug combination compares with alternative therapies. Its main weaknesses were downplaying the side effects and omitting the cost of these very pricey drugs.

[Editor’s Note/Correction: Following publication of this review, a public relations representative that works with AstraZeneca pointed out that the drugs are co-administered, not combined into one drug. That wasn’t made clear in the news release which referred simply to “the combination” or a “combination of two drugs.” We’ve since revised the summary text to read that the study refers to a combination of drugs rather than a combination drug.

In addition, the news release didn’t include the drugs’ costs, so we did an online search in order to give readers a sense of the price. We provided reputable sources for the cost information. AstraZeneca’s representative disputed the cost estimate of $11,899/month and said the wholesale cost for fulvestrant 500 MG is $1,845/month. That cost appears to be accurate whereas the source we referenced was incorrect. We’ve updated that section of the review accordingly. Cost to patients will vary according to their insurance coverage.

We’ve also revised the cost section to reflect that a source noted that palbociclib could “potentially” be one of the top 10 most expensive drugs, not that it currently exists on such a list.]

 

Why This Matters

A diagnosis of breast cancer is stressful to bear. Many women turn to news about current therapies and new trials to try to make sense of their options. For that reason announcements on treatment advances for hormone-receptor-positive, HER2-negative cancer, representing the vast majority of breast cancers, are newsworthy.

This news release is important because it suggests that some women with this type of breast cancer may benefit from delayed progression from a treatment that comes with fewer side effects. It needs to be pointed out, though, that time to progression is not the same as survival.

Criteria

Does the news release adequately discuss the costs of the intervention?

Not Satisfactory

The news release does not mention cost. The wholesale cost for fulvestrant 500 MG is $1,845/month and palbociclib is approximately $9,850. A 2015 report on palbociclib’s cost by a pharmacy benefits manager stated it could potentially be one of the top 10 most costly cancer drugs.

Does the news release adequately quantify the benefits of the treatment/test/product/procedure?

Satisfactory

The news release clearly lays out the advantages of the drug combination over the alternative of fulvestrant with placebo. The primary endpoint of time to progression is reported accurately. The benefits are summed up with these statements:

“Some 67 per cent of the 347 women in the palbociclib plus fulvestrant group showed clinical benefit – either a reduction in tumour size or control of disease for at least six months – compared with 40 per cent of the 174 women in the placebo plus fulvestrant group.”

“Some 19 per cent in the palbociclib plus fulvestrant group had a decrease in tumour size compared with 9 per cent in the placebo plus fulvestrant group.”

Does the news release adequately explain/quantify the harms of the intervention?

Not Satisfactory

The news release downplays a number of side effects named in the journal article. According to the news release, the drug combination apparently has few severe side effects. The news release identifies a drop in white blood cell count as a common, but non-severe, side effect. But when we looked at the study’s table of side effects we found a considerable number of grade 3 or 4 (more serious) adverse events. Some of this is confusing to interpret. For example, the study says that grade 3 or 4 adverse events

occurred in 251 (73%) of 345 patients in the fulvestrant plus palbociclib group and 38 (22%) of 172 patients in the fulvestrant plus placebo group. The most common grade 3 or 4 adverse events were neutropenia [low white blood cell count] (223 [65%] in the fulvestrant plus palbociclib group and one [1%] in the fulvestrant plus placebo group), anaemia (ten [3%] and three [2%]), and leucopenia (95 [28%] and two [1%]).

The study later says,

“Serious adverse events (all causalities) occurred in 44 patients (13%) of 345 in the fulvestrant plus palbociclib group and 30 (17%) of 172 patients in the fulvestrant plus placebo group.”

The study may be drawing a distinction between “serious” and “severe” events and including or not including grade 3 events in these different tallies. Regardless, the release misleads by omission when it calls severe side effects “rare” while not mentioning these relatively common less-severe effects. And that’s leaving aside the issue of grade 1 and 2 side effects that appeared to be quite common and more frequent in the experimental treatment group. The study notes, for example, that “Infections, fatigue, nausea, anaemia, thrombocytopenia, alopecia, rash, and stomatitis, among others, were also more common in the palbociclib group.”

Does the news release seem to grasp the quality of the evidence?

Not Satisfactory

The news release provides a nice summary of the parameters of the randomized controlled trial. However, there are a few important caveats to the research. Notably, the news release fails to note the difference between surrogate outcomes — which this study focused on — and overall survival. There’s ongoing discussion among oncology experts that stalling progression is one goal, but it’s not the most important goal for patients, which is survival. Some question whether delaying progression in metastatic disease for short periods is truly an advance for patients, especially with drugs that carry numerous risk for side effects and huge price tags. In a Milwaukee Journal SentinelSide Effects” column, investigative health journalists John Fauber and Elbert Chu describe the trend of drug companies introducing therapies that may increase “progression-free survival” for a few months but don’t extend life. In many cases, writes Fauber, “The FDA does not routinely push companies to do studies that prove a drug can extend or improve life as a condition of approval. When the agency does, drug companies sometimes ignore it.”

Does the news release commit disease-mongering?

Satisfactory

The news release does not commit any disease-mongering related to the specific type of breast cancer considered in the study.

Does the news release identify funding sources & disclose conflicts of interest?

Satisfactory

The release clearly states that Pfizer funded the study. Pfizer produces palbociclib, one of the drugs studied in the trial.

Does the news release compare the new approach with existing alternatives?

Satisfactory

Throughout the news release, comparison between the drug combination is made with the alternative of taking only one of the drugs, fulvestrant, plus placebo. Several clinical endpoints are reported, all showing the clear advantage of the drug combination.

Does the news release establish the availability of the treatment/test/product/procedure?

Not Satisfactory

The release doesn’t say whether fulvestrant and palbociclib are available or FDA approved.

Does the news release establish the true novelty of the approach?

Satisfactory

The news release appropriately gives the context of the current study as related to previous studies on palbociclib. The novelty established is the new drug combination proves more potent than just one of the drugs alone.

Total Score: 6 of 10 Satisfactory

Comments (1)

Please note, comments are no longer published through this website. All previously made comments are still archived and available for viewing through select posts.

Marc Beishon

March 15, 2016 at 6:09 am

I agree with your points but bear in mind that this is a European/UK report. Palbociclib is not yet approved by the European Medicines Agency, and I don’t think in England fulvestrant is recommended for the metastatic setting ahead of other drugs. Of course these are expensive drugs but they won’t have the same price tags as in the US. Palbociclib/fulvestrant has indeed just got FDA approval so this could have been mentioned but in the context of European and worldwide status.

Reply