Clinical Cases in HER2+ Breast Cancer - Episode 11
Ruta Rao, MD: Dr Jhaveri, back to your patient, what treatment regimens are you thinking about when you first meet this patient, and which would you most likely recommend?
Komal Jhaveri, MD, FACP: When we think about patients who have to be treated in the first-line metastatic setting with HER2 [human epidermal growth factor receptor 2]–positive disease, we have compelling data from the phase 3 CLEOPATRA study that supports the use of the taxane with trastuzumab and pertuzumab, where we saw significant progression-free and overall survival benefits that changed our treatment paradigm. We were using trastuzumab with a chemotherapy with paclitaxel until a decade ago, but these data have been practice changing, and that’s what we’ve been utilizing.
We had multiple attempts with other agents. For example, we tried to see if T-DM1 [trastuzumab emtansine], which is approved in the second-and-beyond setting based on the EMILIA trial and in the third-line-and-beyond setting based on the TH3RESA trial. There was an attempt made in the MARIANNE trial to see if we could utilize T-DM1 [trastuzumab emtansine] alone or T-DM1 [trastuzumab emtansine] in combination with pertuzumab in the first-line setting. However, we did not see any superiority when we compared it with TH [taxane, trastuzumab]; it was similar. The control arm there, TH [taxane, trastuzumab], was our old standard, so it was surprising to see that even T-DM1 [trastuzumab emtansine] plus P [pertuzumab] was not superior to TH [taxane, trastuzumab]. Short of a patient who is not a candidate for a taxane-based chemotherapy because of preexisting disease or preexisting diabetic neuropathy, somebody who is unwilling to accept the adverse effects of chemotherapy, patients who have progressed within 6 months of their adjuvant therapy with a taxane and Herceptin [trastuzumab]—because that was a small subgroup of patients in the phase 3 EMILIA trial where T-DM1 [trastuzumab emtansine] could be offered—I am utilizing the CLEOPATRA-based regimen of a taxane with trastuzumab and pertuzumab. In fact, at our center, Chao Dang had led a phase 2 trial looking at weekly paclitaxel with trastuzumab and pertuzumab. In the CLEOPATRA study, we’d seen about a 14% febrile neutropenia rate with docetaxel and HP [trastuzumab, pertuzumab]. We had seen a 0% febrile neutropenia rate with the weekly Taxol [paclitaxel]–based regimen, so that has been endorsed by NCCN [the National Comprehensive Cancer Network] and ASCO [the American Society of Clinical Oncology]. My preference for this patient would be weekly paclitaxel with HP [trastuzumab, pertuzumab].
Ruta Rao, MD: Dr Tolaney, any additional thoughts or comments when thinking about first-line treatment for this patient?
Sara Tolaney, MD, MPH: I would completely agree. My preference has also been to use a weekly paclitaxel regimen instead of using docetaxel with trastuzumab and pertuzumab. Given the impressive survival data from the CLEOPATRA trial, using pertuzumab-based therapy has been my standard in the first-line setting too.
Transcript edited for clarity.