Ado-trastuzumab emtansine showed similar efficacy as trastuzumab plus taxane as first-line treatment for HER-2–positive advanced breast cancer, according to results of the randomized phase 3 MARIANNE study.
However, ado-trastuzumab emtansine (Kadcyla, Genentech) appeared more tolerable.
“[Ado-trastuzumab emtansine} is an antibody–drug conjugate that induces cell death by inhibiting microtube polymerization,” Edith A. Perez, MD, vice president and head of U.S. medical affairs for Genentech/Roche BioOncology, and colleagues wrote. “[It] has demonstrated superior efficacy and improved tolerability compared with the previous standard of care in two phase 3 trials in patients with previously treated HER-2–positive, advanced breast cancer.”
Edith A. Perez
The MARIANNE study included 1,095 patients from 38 countries with previously untreated HER-2–positive advanced breast cancer.
Researchers randomly assigned patients to three arms: ado-trastuzumab emtansine plus pertuzumab (Perjeta; Genentech; n = 363); ado-trastuzumab emtansine plus placebo (n = 367); or a control regimen that consisted of trastuzumab (Herceptin, Genentech) plus taxane (n = 365).
PFS served as the study’s primary endpoint. Median follow-up was 35 months in each treatment group.
Although ado-trastuzumab emtansine alone or with pertuzumab produced a noninferior PFS compared with the control arm, the two therapies were not superior (ado-trastuzumab emtansine alone vs. control, HR = 0.91; 97.5% CI, 0.73-1.13; ado-trastuzumab emtansine with pertuzumab vs. control, HR = 0.87; 97.5% CI, 0.69-1.08).
Median PFS was 15.2 months for ado-trastuzumab emtansine plus pertuzumab, 14.1 months for ado-trastuzumab emtansine alone and 13.7 months for the control regimen.
The addition of pertuzumab to ado-trastuzumab emtansine did not improve PFS (HR = 0.91; 97.5% CI, 0.73-1.13).
In the control arm, 31 patients died and 200 experienced disease progression. In the ado-trastuzumab emtansine monotherapy group, 11 died and 225 experienced progression. Among those assigned ado-trastuzumab emtansine plus pertuzumab, 23 died and 194 experienced progression.
Grade 3 or higher adverse events occurred in 54.1% of patients in the control arm, compared with 45.4% among those assigned to ado-trastuzumab emtansine monotherapy and 46.2% among those assigned ado-trastuzumab plus pertuzumab.
“[Ado-trastuzumab emtansine]–containing regimens demonstrated noninferior — but not superior — PFS compared with treatment with trastuzumab plus taxane,” the researchers wrote. “On the basis of the improved tolerability and noninferior PFS observed with [ado-trastuzumab emtansine], it may provide an alternate treatment option to trastuzumab plus taxane in patients with HER-2–positive metastatic breast cancer who are considered not suitable for treatment with the preferred regimen [of] pertuzumab, trastuzumab and a taxane.” – by Andy Polhamus
Disclosure: Perez reports employment with and stock ownership in Genentech. Please see the full study for a list of all other researchers’ relevant financial disclosures.