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Study results overplayed in announcement on investigational HER2-positive breast cancer drug

Tucatinib (ONT-380) progressing in pivotal trial against HER2+ breast cancer

Our Review Summary

This news release from the University of Colorado’s medical center reports on the results of a phase 1 clinical trial involving 50 women who took the investigational drug tucatinib to treat HER2-positive breast cancer. All of the women in the study previously had taken other cancer drugs, averaging five prior treatment regimens. The news release noted that the data came from a phase 1 study which was primarily focused on establishing the safety of the drug and ensuring that it had some effect; however, it provided confusing information about tucatinib’s effects on the breast cancer’s progress, offered no specific information about potential harms or availability and included inappropriately enthusiastic language about the drug’s importance, given the small size and short study period. In particular, the release quotes one of the study’s authors as saying that “there are women who are alive today because of this drug,” a statement that seems somewhat overblown given the preliminary nature of these findings.


Why This Matters

The drug under investigation in this study is meant to treat one of the most difficult and aggressive types of breast cancers; HER2-positive strains account for about one-in-five breast cancers, are more likely to occur in younger women and are more likely to metastasize to the brain. The study involved women who already had undergone treatment with several other anti-cancer drugs. In addition, the molecular characteristics of this drug make it a candidate for delaying or preventing brain metastasis. The study results led to FDA “fast-track” status for the drug.


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

Not Satisfactory

The news release provides no information about how much tucatinib treatment might cost. If it’s not too soon to promote the potential benefits of a drug it’s not too soon to provide cost estimates.

[Editor’s note: We had originally rated this criteria Not Applicable since it is an investigational drug in very early trials and it’s plausible costs are unknown. However, the rating has been revised to be consistent with past reviews and to reflect our general position that costs (or cost estimates based on similar drugs or treatments) should be presented.]

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

Not Satisfactory

The discussion of benefits is somewhat confusing. The news release says that 27% of the women treated with tucatinib “saw clinical benefit” from the drug. However, the article itself states that evaluation of the drug’s impact was possible for only 35 women, and of these women, 20 showed no progression of their disease, while there was a “partial response” for three women, meaning that their tumors shrank by at least 50%. The most important benefit identified by the original study actually was that tucatinib caused less frequent and less severe side effects (including diarrhea and rash) than the alternatives currently used in treating these types of breast cancers. The news release barely mentioned this finding, stating simply that the drug “has a very favorable side effect profile” without explaining what that means.

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

Not Satisfactory

According to the original study, 30% of the patients had to have their treatments “interrupted,” usually due to effects on liver function, although the study says the drug treatment was “almost always” re-initiated, and no one had to be removed from the drug entirely. None of these problems was mentioned in the news release, which also offers no specific information about the frequency or severity of side effects.

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

Not Satisfactory

The news release states that the trial involved 50 patients overall, but does not explain that the study produced data that could be evaluated for only 35 patients. The release does note that this was a phase 1 trial. Despite providing this information, however, the language used in the news release seems to imply a level of significance for this study greater than one would expect for a study of 50 patients who were evaluated, in some cases, after as little as 24 weeks.

Does the news release commit disease-mongering?

Not Applicable

The news release does not commit disease mongering, but it also provides no information about what percentage of breast cancers are of the HER2+ variety. (According to the Mayo Clinic website, about 20% of breast cancers have the HER2+ gene mutation, which makes them more aggressive.) Thus, a naïve reader might be inclined to think that the drug would benefit a larger percentage of breast cancer patients than is likely to be the case.

We won’t give credit or dock points in this case; we’ll rate it Not Applicable.

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

Not Satisfactory

The news release mentions Array BioPharma, which originally developed tucatinib, but it does not state specifically that Array provided the funding for this study, nor does it explain that three of the authors of the original paper are Array employees. It does note that its only source, Dr. Virginia Borges, director of the Breast Cancer Research Program and Young Women’s Breast Cancer Translational Program at the University of Colorado Cancer Center, “has been a major driver of the drug’s development from its invention at Array Biopharm in Boulder, CO and now through clinical trials of the drug, which is licensed to Cascadian Therapeutics of Seattle, WA.”

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

Not Satisfactory

The release quotes researcher Virginia Borges, MD, MMSc, director of the university’s Breast Cancer Research Program saying that trials of other drugs have been “lackluster” in their effects on breast cancers positive for both HER2 and estrogen receptors. Borges further suggests that tucatinib is more effective than other drugs in preventing brain metastases. The release notes that because tucatinib is a “small molecule,” it can pass through the blood-brain barrier to interfere with brain metastasis, which is more common in HER2-positive breast cancers. However, there is no specific comparison of this ability with other drugs currently in use.

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

Not Satisfactory

No information in the news release gives an indication as to when (or if) tucatinib might be widely available.

The lead researcher’s comment that “I think this drug has an extremely high likelihood of being approved for women with HER2+ breast cancer for use after previous treatments” is problematic given that the investigative drug is still in early trials and has not yet been FDA approved.

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


The news release suggests that tucatinib is unusual because it is taken in pill form, meaning women do not need to visit infusion centers for treatment. It also suggests that tucatinib is unusual because of its small molecular size, enabling the drug to pass the blood-brain barrier. However, no information is provided about how many, or how few, other cancer drugs can be taken in pill form or whether any other anti-cancer drugs currently in use or in testing also can pass through the blood-brain barrier.

Does the news release include unjustifiable, sensational language, including in the quotes of researchers?

Not Satisfactory

The use of unjustifiably glowing language arguably is the news release’s most serious flaw. In particular, the subhead of the release quotes Dr. Borges as saying, “There are women who are alive today because of this drug.” Later in the release, she predicts that tucatinib “could be a substantially practice-changing drug.” While either statement could be true, drawing such sharp conclusions from evaluations of 35 women, only three of whom actually experienced tumor shrinkage, seems premature.

In addition, the investigator is quoted saying, “And it’s going to be an especially important drug due to its ability to control brain metastases”

It’s important to note the comments about crossing the blood brain barrier that come from the “Translational Relevance” section of the study. The authors note that in preclinical studies with intracranial tumor models, mice treated with the investigational drug combined compared with 2 other oral agents (lapatinib or neratinib) showed a survival benefit when each drug was given at maximum dose. They do not note any study or evidence showing that this investigational agent has shown benefit in terms of treating brain metastasis in human patients, so that language in the release also appears unjustified.

Because it seems tucatinib would be used for a particularly vulnerable group of women — those diagnosed at younger ages and with more aggressive and difficult-to-treat cancers — it seems especially important that those writing about the drug exercise caution and avoid overplaying study results.

Total Score: 1 of 9 Satisfactory


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