ASCO 2026 | HER2CLIMB-05: subgroup analyses of tucatinib, trastuzumab & pertuzumab in HER2+ mBC

This was the HER2CLIMB-05 presentation, and it was an update from previously presented data. And what we really updated was efficacy as well as objective response rate and duration of response in some key important subgroups. As you remember, the HER2CLIMB-05 really was looking at first-line maintenance. So once patients complete taxane with trastuzumab and pertuzumab, they’re progression-free after four to eight cycles of taxane, and they’re dropping the taxane out, this is when they can enter this maintenance regimen. Patients are randomized to either getting HP alone, with or without endocrine therapy, depending on whether they have HR positive status, and that was left at the discretion of kind of local institutional standards, or HP in combination with tucatinib, again, also allowed to have endocrine therapy in that arm as well. Previously presented data was that progression-free survival was improved from 16.3 to 24.9 months, and so this was an absolute magnitude of benefit of 8.6 months. But new data was in the overall population, those that had a valuable scan, so a baseline scan and an on-treatment scan, that the objective response rate was improved from 15.2% to 22.6% with the addition of tucatinib, as well as the duration of response for those responders was lengthened from 16.9 months to 20.9 months. We also looked at a couple of key subgroups, HR positive versus HR negative disease, patients that either had or did not have brain metastases at baseline and patients that had de novo or recurrent metastatic disease. And what we found for the subset of patients that had HR positive disease, that progression-free survival was lengthened by 6.9 months. For those that had HR negative disease, it was lengthened by 12.3 months. And then what was really interesting is we looked at that subset of patients that had HR positive disease and looked at whether they received concurrent endocrine therapy or not. And interestingly, the majority of our patients actually did not receive endocrine therapy. The benefit, though, existed regardless of whether patients received endocrine therapy. Hazard ratio was 0.724 if they did receive, 0.658 if they did not. So benefit really persisted regardless. We did see progression-free survival be really quite a bit longer if you did receive endocrine therapy, really highlighting the importance of receiving endocrine therapy in this subgroup. And then in terms of brain metastases, about 12.4% of patients in this first line trial had brain metastases at baseline. And we saw for those patients that had brain metastases at baseline that progression-free survival was more than doubled with the addition of tucatinib from 4.2 to 8.5 months. In the patients that did not have brain metastases, the hazard ratio actually was identical, 0.64 in favor of adding tucatinib with a 9.1-month benefit there as well. And then a similar story told regardless of de novo or recurrent disease, 16.8 up to 28.9 months or 12.7 up to 21.3 months. So really our overall takeaways was that regardless of whether patients had hormone receptor expression, regardless of whether they had brain metastases or not, or whether their metastatic disease was de novo or recurrent, that the addition of tucatinib to first-line maintenance therapy with HP benefited patients. And this really is an emerging new standard of care in the first-line maintenance space.

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