Cancer and its treatments can be challenging for reporters to cover. At times, this can lead to a misinterpretation of study findings or incorrect explanations of how a drug works or who it is for. In this article, there is a litany of errors that begins in the headline and continue on into the story. The end result is an article that inaccurately tells readers there is a new cancer drug, BYL719/alpelisib, that cuts the risk of death by 35 percent in patients with a breast cancer gene mutation. The drug improved progression-free survival, which is not the same as survival and does not necessarily reflect “risk of death.” The patients have not been followed long enough to know if the ones who received BYL719/alpelisib along with Faslodex (fulvestrant), an approved cancer drug, lived longer than those who received Faslodex alone.
Also, BYL719/alpelisib is not for patients with an inherited gene mutation. It is for patients who have breast cancer cells with a type of genomic mutation that is seen in about 40 percent of patients with hormone-sensitive breast cancer. The words genomic and genetic are not interchangeable and do not mean the same thing.
Breast cancer is the most common cancer diagnosed in women and the second leading cause of cancer death. Most women can be treated with a combination of surgery, hormones, radiation and chemotherapy depending upon the findings on imaging and pathology. However, some patients progress despite standard therapy and for these women new treatments that improve outcomes would be warranted. In this study, one of the common breast cancer types, hormone receptor positive, HER2 negative, is further characterized by the presence of a specific mutation, PIK3CA. The study reported compares treatment with a currently approved drug, fulvestrant, and the addition of a new drug targeting this mutation, alpelisib. The favorable outcomes reported in this article come from a meeting presentation. The available information about this drug, while promising, does not provide sufficient information to know whether this drug will end up as part of newer treatment options for women with this form of breast cancer who have progressed despite standard therapy. Both investors and patients deserve to know this.
Although BYL719/alpelisib has not been approved by the FDA, it’s safe to assume that the drug will be costly, and there should have been some discussion of this. The only PI3K inhibitor approved as a cancer treatment, for certain types of lymphoma, is an injection and retails for about $4,700 per vial. Many vials may be given over the course of treatment.
The first paragraph says the drug BYL719/alpelisib can “cut the risk of death or disease progression by more than a third in breast cancer patients with a hard-to-target gene mutation.”
In the second paragraph we learn this effect was seen when BYL719/alpelisib was combined with Faslodex, a drug currently used to treat advanced breast cancer. In patients who received both drugs, the median progression-free survival was 11 months. It was 5.7 months for patients on Faslodex alone.
In the next paragraph, we are told the drug combination cut the risk of death or progression by 35 percent, but there are no statistics about the absolute number of people who died included in the story.
To learn more, we looked at the news release and study abstract put out by the organizers of the European Society for Medical Oncology (ESMO) 2018 conference in Munich, where the study was presented. This allowed us to discover that the study randomized 572 postmenopausal women or men with hormone-sensitive, HER2-negative advanced breast cancer. Of these, 341 were found to have the PIK3CA mutation when their tumor was tested. The findings reported from the study were specific to that group of patients who had the mutation. The news release explains that 36% of 262 patients with this mutation responded to the combination.
We also learn, in a quote from the study’s lead author, that “the follow-up is short so we cannot say whether there is a long-term survival benefit.” They hope that the progression-free survival will translate into an overall survival benefit–but they don’t know.
In short: There is no data to support the headline’s claim that BYL719/alpelisib reduces the risk of death from breast cancer by 35 percent.
The article quotes the head of cancer drug development for Novartis as saying, “We don’t see as much diarrhea, we do not have CNS (central nervous system) side effects, we do not have liver effects.”
What any of this means is not clear. As much diarrhea as compared to what? Were they expecting CNS or liver effects? Do other PI3K inhibitors have those side effects? None of that is spelled out.
Once again, we returned to the ESMO news release and abstract to learn more. This told us the most frequent side effects were hyperglycemia, nausea; decreased appetite and rash.
The article never explains that this was a phase III clinical trial and that the primary endpoint was progression-free survival. It’s important that news stories point out progression-free survival is a surrogate outcome, and should not be confused with overall survival.
It also doesn’t include any information about how many people were in the study or how many who were enrolled were found to have the mutation in their tumor tissue that the drug targets (see quantified benefits above to see what we found via the news release).
The article provides sufficient information to make clear that this is a treatment for a specific group of women with breast cancer with this PIK3CA mutation. More could have been said about what percent of breast cancer patients this may represent, though.
The article quotes Farbrice Andre. It does not mention that Andre is the lead author of the study. It also does not mention that Andre received a grant from Novartis while the study was being conducted, which is noted in the disclosure section of the abstract.
The article also quotes the head of cancer drug development at Novartis.
There are no quotes from researchers or experts not involved with the study.
The study is comparing the combination of Faslodex and BYL719/alpelisib to Faslodex alone. It’s not clear if there are other treatment options for this patient population or if Faslodex alone would be the standard of care for these patients at this point in their treatment.
The article states that Novartis plans to file for approval for the drug this year.
We learn–via the lead researcher–that this trial provides the “most encouraging” results to date in a study looking at a PI3K inhibitor in breast cancer. That establishes novelty, but we think the story should have sought independent expert viewpoint to provide context on the limitations of the results, which were based on progression-free survival and not overall survival.
It does not include the information that one other PI3K inhibitor is currently on the market and used to treat a type of lymphoma.
The reporter appears to have interviewed one source directly. However, one source’s quote is taken directly from the drug company’s news release, and is not attributed to the release. This statement appears in both the news story and the news release:
“These data have the potential to allow physicians to address an unmet need in this patient population by using a biomarker-driven treatment to inform their sequencing decisions,” Andre added.
For this reason, the story scores not satisfactory on this criterion.