Post-Conference Perspectives: Optimizing the Management of HER2+ Metastatic Breast Cancer - Episode 7
Erika P. Hamilton, MD: The specific value of CNS [central nervous system] penetration is certainly to treat those patients who already have brain metastases. They really do not have great treatment options. We often use neratinib or lapatinib in these settings, but even the benefit there is short-lived. These patients ultimately progressed. It can be hard to tolerate those drugs. The other benefit really is the fact that we know that 50% of patients will develop brain metastases. This is a very exciting regimen for even those patients who don’t have brain metastases, because the reason people develop them is that the brain is a sanctuary, or other agents don’t get there. If we use something like this earlier on, it really could conceivably prevent brain metastases. We always love prevention instead of just treating something once it happens.
The adverse effects of HER2CLIMB predominantly came from the other agents that we know of. Capecitabine causes hand-foot syndrome. It can also cause a little bit of nausea. This is a chemotherapy pill, a little bit of diarrhea. It goes through the GI [gastrointestinal] tract, etc, and palmar-plantar erythrodysesthesia or redness and peeling on the palms of the hands and the soles of the feet. It didn’t really appear that tucatinib worsened these symptoms. Trastuzumab we’re all quite familiar with. It’s an IV [intravenous] infusion. It’s antibody against HER2. The main thing we have to watch out for with trastuzumab is decreases in ejection fraction, or how well the heart squeezes. Again, tucatinib did not worsen this. The adverse effects specific to tucatinib had a little bit of overlap with liver function tests increasing. These were all reversible. But in combination with the capecitabine, we did see some patients who had to hold or dose reduce for liver function test abnormalities.
HER2CLIMB met all of its end points. It met for progression-free survival of an improvement of a little over 2 months. It met for overall survival in the all-comer population with an improvement of overall survival of 4½ months, and it met its end point for progression-free survival in those patients with brain metastases. Across the board, it was positive.
The HER2CLIMB results are practice changing. I think we will see an approval of this agent shortly, based on these results. This is practice changing, not only for our patient population with brain metastases but also for those patients post—T-DM1 [trastuzumab emtansine] and chemotherapy trastuzumab-pertuzumab who don’t, hopefully as more of a prevention strategy for future brain metastases. It’s a highly active combination, it’s easy to give in the clinic, and patients generally feel well on it.
Transcript Edited for Clarity