The new guidelines reflect the contributors' firsthand experiences developing new targeted therapies across cancer subtypes.

"For some subtypes of breast cancer, including HER2-positive or triple-negative, the incidence of brain metastases in patients who have recurrent/metastatic disease approaches 50 percent. Making progress against these subtypes of breast cancer very much depends on developing new and better treatments for brain metastases. Our hope is that by providing investigators with a roadmap for clinical trial design, we can encourage more studies focused on this challenging clinical problem. These new guidelines aim to fundamentally change drug development for advanced cancers," says Nancy U. Lin, MD, clinical director of the Breast Oncology Center at the Susan F. Smith Center for Women's Cancers at Dana Farber Cancer Institute.


"Brain metastases are also very common in lung cancer and it would be very frustrating to have a patient with controlled brain disease excluded from a trial that could benefit them," says Camidge, who has been intimately involved with the development of targeted therapies against non-small cell lung cancer, including crizotinib, alectinib and brigatinib. "Similarly, we have also started to see anecdotal evidence of new targeted therapies working against metastases in the brain, but current clinical trial design leaves holes in the data. For example, many trials don't standardize capturing information on the use of prior radiotherapy in the brain and so in such cases it has been very hard to tell whether benefit in a patient's CNS disease was due to radiotherapy or to the drug. When trying to choose between treatments, it was clear that we needed to get serious about demanding better data quality with respect to the brain."

The new guidelines may be especially important for clinical trials addressing patients with cancer types that commonly spread to the brain, including non-small cell lung cancer, small cell lung cancer, HER2+ and triple-negative breast cancer, and melanoma, all of which become especially dangerous once reaching the central nervous system. In these conditions, the guidelines write that, "Exclusion of [brain metastasis] patients could remove half to two-thirds of the stage IV population."

"We all hope that these guidelines will represent a turning point in cancer drug development," Camidge says. "Over the next few years, changes in clinical trial design centered around generating and acting on early signals of a drug's CNS activity or lack thereof should radically decrease risk and increase the therapeutic potential of new drugs across many different cancers."

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