Potential new kidney cancer drug said to be “more effective than standard of care,” but only if you’re a mouse

Our Review Summary

This is a mouse study of a product called PT2399 from a class of drugs called HIF-2 inhibitors that have purportedly been shown to be “more effective and better tolerated than the standard of care drug” in the treatment of kidney cancer. While this is promising research, appropriate language to say that this is a very small, very preliminary and non-definitive rodent study was largely missing. A novel compound can be very exciting for the researchers, those who are making and promoting it, and the institution that has a financial interest in its success, but that excitement needs to be tempered with a ‘reality check’ on the challenges of translating animal research to human outcomes. from observers unconnected to the research.  Without that, the news release reads as a mere PR exercise, designed to generate premature (yet possibly unfounded) excitement.

[Editor’s note: The news release says, “In the study in Nature, investigators show that HIF-2 inhibition was able to control metastatic kidney cancer even after 7 lines of prior therapy. See video.”  However, the release contained no link to the video so the review was completed without viewing the video.]

Why This Matters

If it is true that nearly 400,000 Americans are currently diagnosed with kidney cancer, and it produces an additional 60,000 new cases each year (according to the National Cancer Institute) then this research could be of a very large public health importance. Unfortunately, this release doesn’t discuss the effectiveness and problems with current treatment in humans.

The study’s key findings that the “HIF-2 inhibitor was more active than sunitinib and that it was active against tumors progressing on sunitinib” as well as being “better tolerated” could be a real advance if such advantages are later shown to be seen in people. The key bit of missing information is that mice that gain weight on the drug (when the comparator mice were “sickly and lost weight”) are still mice, and no amount of tweaking of these results will magically transform results that are directly applicable in humans.

Even if new biomarkers are identified that determine which mice would be most likely to benefit from HIF-2 therapies, we may be decades away from having a compound that is proven to work in humans. Sometimes rodent research can be terribly hopeful, and described in hyperbolic terms, but turn out later not to be terribly helpful. Institutions that present animal research as applicable to humans run the risk of raising false hopes in desperate patients.