PracticeUpdate: There are interesting data on health-related quality of life among patients with HER2+ metastatic breast cancer treated with tucatinib. Where does tucatinib fit into the current paradigm for HER2+ disease?
Dr. Schwartzberg: One area where we've made a lot of progress in the last year or two has been in the HER2-positive advanced breast cancer space. We have new drugs in this area that are very exciting because they have meaningful impacts on our patients with this disease. One of the drugs and one of the trials that has been most impactful is the HER2CLIMB trial, which looked at a new small molecule, HER2 inhibitor, tyrosine kinase inhibitor called tucatinib in combination with capecitabine and trastuzumab.
And this study, which was reported over the last year in multiple meetings and published, showed that that combination in patients who had been heavily pre-treated, and by heavily pre-treated in the HER2 space I mean all patients in HER2CLIMB had received trastuzumab, had received pertuzumab, and T-DM1 in the metastatic setting, and that was a condition for enrollment in HER2CLIMB. Then they were randomized to receive tucatinib, capecitabine and trastuzumab, or placebo, trastuzumab and capecitabine. It was a two-to-one randomization. And what the results showed was an improvement in overall survival of 34% with the addition of tucatinib, with a 2-year survival of 45% versus 27%, a median overall survival of 21.9 months for tucatinib versus 17.4 months without tucatinib and the progression-free survival also improved [by] 46%.
One of the most interesting things about HER2CLIMB was that it allowed patients with brain metastases, either pre-treated or not treated. And almost half the patients on this trial had brain metastases, which as we know, is a consequence of HER2-positive advanced breast cancer after multiple treatments. What we saw there was that the brain metastases group also had a progression-free survival that was improved by over 50%. So this is an unmet need in HER2-positive breast cancer that we see tucatinib fulfilling. So at ESMO this year, the investigators looked at whether or not quality of life was impacted by the addition of tucatinib to trastuzumab and capecitabine. Now we have a treatment regimen that prolongs survival, do we do that at the expense of patients' quality of life? Which we certainly don't want. We want to maintain quality of life and maintain quantity of life as well, which we've already proven in the HER2CLIMB trial.
In HER2CLIMB, investigators looked at the health-related quality of life using a tool called the EQ-5D-5L tool. And this tool was administered to patients at baseline, at cycle three, and then every second cycle after that. And ESMO reported the results of the quality of life studies. What they found was that the health-related quality of life was maintained throughout the treatment and was not different between the two arms, whether or not they had tucatinib or placebo added to capecitabine and trastuzumab. And the time to meaningful worsening, which in this particular tool is a seven-point reduction in the survey answers, was not different for the patients who received tucatinib versus those that received placebo.
When they looked at sub-scales, like pain and self-care and mobility and doing usual activities, again, they saw no difference. And so what this proves is that there was no impact in a negative way of adding tucatinib to the regimen in the HER2-positive metastatic breast cancer patients. And these patients were able to enjoy the same quality of life and also have improved outcomes in terms of progression-free survival, controlled brain metastases and overall survival, while getting the more intensive regimen.