BCC 2021 | Can we prevent brain metastases in breast cancer?
Nancy Lin, MD, Dana-Farber Cancer Institute, Boston, MA, discusses the latest progress in developing strategies to prevent brain metastases in patients with breast cancer. Prevention in early-stage disease remains a challenge, with clinical trials of trastuzumab, pertuzumab, lapatinib, and trastuzumab emtansine (TDM1) all failing to provide evidence of efficacy against central nervous system (CNS) relapse. More progress has been seen in the metastatic HER2-postive breast cancer setting. Two recent randomized trials in advanced HER2-positive breast cancer have shown promising CNS results: the Phase III NALA trial (NCT01808573) of neratinib plus capecitabine and the Phase II HER2CLIMB trial (NCT02614794) of tucatinib with capecitabine and trastuzumab. This interview took place during the 17th St. Gallen International Breast Cancer Conference.
Transcript (edited for clarity)
At the St. Gallen meeting this year, I discussed where we are in terms of progress with respect to preventing brain metastases, both in the early-stage and metastatic settings. Unfortunately in the early-stage setting, we really haven’t made much progress. And what I showed was that in the clinical trials, testing adjuvant trastuzumab, pertuzumab, lapatinib and now TDM1, we really have seen no evidence of prevention of CNS relapse with no difference in the rates between the control arm and the experimental arms...
At the St. Gallen meeting this year, I discussed where we are in terms of progress with respect to preventing brain metastases, both in the early-stage and metastatic settings. Unfortunately in the early-stage setting, we really haven’t made much progress. And what I showed was that in the clinical trials, testing adjuvant trastuzumab, pertuzumab, lapatinib and now TDM1, we really have seen no evidence of prevention of CNS relapse with no difference in the rates between the control arm and the experimental arms. There was a suggestion of a difference in the neratinib ExteNET trial, but this was in a subset analysis and we’re still waiting for results in terms of the planned tucatinib trials in the adjuvant setting, which are just underway.
In patients who have metastatic HER2-positive breast cancer, we are seeing some glimmers of hope that we may be able to prevent CNS metastases. These data come from both the NALA trial, which compared neratinib-capecitabine versus lapatinib-capecitabine that showed a prolongation to time to CNS intervention and a reduction in the incidence of CNS metastases. And then more recently in the HER2CLIMB trial, which showed a prolongation of time to CNS progression or death, and actually also a prolongation to time to new brain metastases in this trial.
In terms of how we improve outcomes for patients with brain metastases, I think first and foremost, we need to include patients with brain metastases into our clinical trials at all phases of testing, because this is really the only way that we can make progress and understand what works and doesn’t work in patients with brain metastases, as well as the prevention setting.
The other important advance would be really developing drugs specifically to target the CNS and whether this is developing drugs that penetrate the blood-brain barrier better or understanding better the mechanism by which breast cancer travels to the brain, or is able to survive in the brain and targeting those pathways specifically, I think that trying to stumble upon CNS-active drugs without a deliberate process will be much slower than trying to do this in a thoughtful and purposeful way.
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Disclosures
Clinical trial/grant funding (to institution): Genentech, Seattle Genetics, Merck, Pfizer
Consulting/advisory board: AstraZeneca, Daichii Sankyo, Puma, Prelude Therapeutics, Seattle Genetics, Denali Therapeutics, California Institute for Regenerative Medicine
