Treatment with trastuzumab, pertuzumab, and docetaxel appears to yield similar efficacy to trastuzumab emtansine in patients with ErbB2-positive breast cancer.
Treatment with trastuzumab (Herceptin), pertuzumab (Perjeta), and docetaxel (Taxotere) appears to be comparable to treatment of trastuzumab emtansine (T-DM1) in patients with ErbB2-positive breast cancer, according to the results of the phase 2 PREDIX HER trial (NCT02568839).
Results from the trial indicated that there was not a statistically significant difference in pathological complete response (pCR) between cohorts (P = .82). In the standard group, 45.5% of patients achieved a pCR (n = 45; 95% CI, 35.4%-55.8%) and 43.9% of patients achieved a pCR (n = 43; 95% CI, 33.9%-54.3%) in the investigational group.
“The first report from the PREDIX HER2 trial shows that standard neoadjuvant treatment with docetaxel, trastuzumab, and pertuzumab was equivalent to T-DM1 monotherapy, while T-DM1 demonstrated a more favorable toxic effect profile. With appropriate patient selection and dynamic therapy adaptation based on early response assessment, T-DM1 may have the potential to become a successful strategy for treatment de-escalation,” the study investigators said.
The randomized, multicenter, open-label study’s population consisted of of 99 women in the standard group, and 98 women in the investigational group. Throughout the trial, 92 patients in the standard group and 94 in the investigational group received all 6 courses of treatment scheduled. However, 17 switched from the standard treatment arm to treatment with T-DM1 during the study, due to stable disease (n = 4) and grade 3 or higher toxicities (n = 13). Additionally, 9 crossed over from the T-DM1 arm to the standard arm because of stable disease (n = 4), tumor progression (n = 3), and grade 3 or higher toxicities (n = 2).
To enroll on the trial, patients needed to have an ERBB2-positive tumor that was larger than 20 mm and/or morphologically verified lymph node metastases. Additionally, an ECOG performance status of 0 or 1 was required.
The primary end point of the trial was pCR to primary medical treatment and the secondary end points included event-free survival, overall survival, and distant disease-free survival.
Additionally,a subgroup analysis was conducted that identified higher pCR rates in patients hormone receptor (HR)–negative disease vs HR-positive. Patients who were HR-negative (n = 45/72) had a pCR rate of 62.5% compared with 36.0% (n = 45/125) in those who were HR-positive patients. Investigators found that pCR occurred more frequent in patients who were HR-negative (62.5%; n = 45/72), including 66.7% (n = 22/33)in the standard group and 59.0% in the investigational group (n = 23/39). By comparison, the HR-positive group had a pCR rate of 36.0% (n = 45/100), including 36.4% (n = 24 of 66) and 35.6% (n = 21/59; P=.001) in the standard and investigational groups, respectively.
The median follow-up time after cutoff was 40.4 months (range, 2.2-66.5). Additionally, event-free survival was not significant between groups. Seventeen events that occurred during the study, including local progression of primary breast tumor during neoadjuvant treatment (n = 3), all of which took place in the investigational group. Moreover, post-operative events included diagnosis of local-regional relapse (n = 4), collateral breast cancer (n = 4), and distant metastases (n = 5).
Between groups, T-DM1 was found to be better tolerated, with a higher incidence of adverse effects (AEs) taking place in the standard cohort vs the investigational cohort. Grade 3 or 4 AEs occurred in 39 (39.4%) patients in the standard group, the most frequent being diarrhea, mucositis, exanthema, and sensory neuropathy. In the investigational group, 10 (10.1%) patients had grade 3 or 4 AEs, the most common being headache, mucositis, sensory neuropathy, and increase of liver transaminases. No deaths occurred during this treatment.
Investigators also had patients fill out health-related quality of life (HRQoL) questionnaires, the response rate of which was 99.0% at baseline and 86.9% following cycle 6. There were no notable differences in HRQoL at baseline. Following 6 cycles of treatment, investigators identified a statistically significant difference favoring the investigational group on 13 of the EORTC QoL questionnaire C30 and BR23 variables. However, 3 months post-surgery, a statistically significant difference was observed in favor of the standard group for 6 variables
Hatschek T, Foukakis T, Bjöhle J, et al. Neoadjuvant trastuzumab, pertuzumab, and docetaxel vs trastuzumab emtansine in patients With ERBB2-positive breast cancer: a phase 2 randomized clinical trial. JAMA Oncol. Published online ahead of print, June 24, 2021. doi:10.1001/jamaoncol.2021.1932