Trastuzumab Emtansine With or Without Pertuzumab Versus Trastuzumab Plus Taxane for Human Epidermal Growth Factor Receptor 2–Positive, Advanced Breast Cancer: Primary Results From the Phase III MARIANNE Study

Abstract

PurposeTrastuzumab and pertuzumab are human epidermal growth factor receptor 2 (HER2) –targeted monoclonal antibodies, and trastuzumab emtansine (T-DM1) is an antibody–drug conjugate that combines the properties of trastuzumab with the cytotoxic activity of DM1. T-DM1 demonstrated encouraging efficacy and safety in a phase II study of patients with previously untreated HER2-positive metastatic breast cancer. Combination T-DM1 and pertuzumab showed synergistic activity in cell culture models and had an acceptable safety profile in a phase Ib and II study.MethodsIn the MARIANNE study, 1,095 patients with centrally assessed, HER2-positive, advanced breast cancer and no prior therapy for advanced disease were randomly assigned 1:1:1 to control (trastuzumab plus taxane), T-DM1 plus placebo, hereafter T-DM1, or T-DM1 plus pertuzumab at standard doses. Primary end point was progression-free survival (PFS), as assessed by independent review.ResultsT-DM1 and T-DM1 plus pertuzumab showed noninferior PFS compared with trastuzumab plus taxane (median PFS: 13.7 months with trastuzumab plus taxane, 14.1 months with T-DM1, and 15.2 months with T-DM1 plus pertuzumab). Neither experimental arm showed PFS superiority to trastuzumab plus taxane. Response rate was 67.9% in patients who were treated with trastuzumab plus taxane, 59.7% with T-DM1, and 64.2% with T-DM1 plus pertuzumab; median response duration was 12.5 months, 20.7 months, and 21.2 months, respectively. The incidence of grade ≥ 3 adverse events was numerically higher in the control arm (54.1%) versus the T-DM1 arm (45.4%) and T-DM1 plus pertuzumab arm (46.2%). Numerically fewer patients discontinued treatment because of adverse events in the T-DM1 arms, and health-related quality of life was maintained for longer in the T-DM1 arms.ConclusionT-DM1 showed noninferior, but not superior, efficacy and better tolerability than did taxane plus trastuzumab for first-line treatment of HER2-positive, advanced breast cancer.

Efficacy and tolerability of trastuzumab emtansine in advanced human epidermal growth factor receptor 2–positive breast cancer

“…12 In that study, previously untreated patients with HER2+ metastatic breast cancer were randomised to one of the three arms: control (trastuzumab plus taxane), T-DM1 alone, or T-DM1 plus pertuzumab. Although the results revealed that grade 3 or higher adverse events were lower in the T-DM1 arm, efficacy data on PFS were similar in all three arms, at 13.7 months, 14.1 months, and 15.2 months, respectively.…”

Adverse Events of Trastuzumab Emtansine (T-DM1) in the Treatment of HER2-Positive Breast Cancer Patients

“…Finally, in the MARIANNE trial, 1,095 patients with HER2-positive advanced BC who had received no prior therapy for advanced disease were randomly assigned, in a 1: 1:1 ratio, to 1 of the following 3 groups: T-DM1 plus placebo, T-DM1 plus pertuzumab, and a control arm of trastuzumab plus a taxane [10]. According to this study, the incidence rate of grade 3 AEs was higher in the control group (54.1%), compared to the T-DM1 (45.4%) and the T-DM1 plus pertuzumab group (46.2%) [10].…”

Novel treatment strategies for patients with HER2‑positive breast cancer who do not benefit from current targeted therapy drugs (Review)

“…T-DM1, a second-generation antibody, has attracted great interest from researchers for its effective role as an adjuvant and neoadjuvant (34). The phase III EMILIA study and RESA study proved that T-DM1 was efficacious as afunctional treatment and facilitated better prognosis and improvements in health-related quality of life (35)(36)(37).…”