The combination of ado-trastuzumab emtansine and pertuzumab demonstrated significant antitumor activity and an acceptable safety profile in patients with HER-2–positive, locally advanced breast cancer, according to results of a phase 2a study.
“These findings validate the results observed in the preclinical setting and support the evaluation of [ado-trastuzumab emtansine] with pertuzumab in the ongoing phase 3 MARIANNE trial,” the researchers wrote.
Researchers evaluated the safety and efficacy of 3.6 mg of ado-trastuzumab emtansine (Kadcyla, Genentech), commonly called T-DM1, in combination with pertuzumab (Perjeta, Genentech) once every 3 weeks. The pertuzumab regimen consisted of an 840-mg loading dose, followed by subsequent 420-mg doses.
The analysis included 64 patients with HER-2–positive, metastatic breast cancer. Forty-three patients had advanced metastatic breast cancer and had undergone prior treatment; these patients had undergone a median of six prior nonhormonal therapies, and 86% had received trastuzumab (Herceptin, Genentech) in the neoadjuvant setting. The other 21 patients in the cohort were in the first-line setting.
Researchers reported an objective response rate of 41% overall, 33% among patients with advanced disease and 57% among first-line patients. Median PFS was 6.6 months overall, 5.5 months among patients with advanced disease and 7.7 months among first-line patients.
Exploratory biomarker analyses indicated that patients with above-median tumor HER-2 mRNA levels had higher objective response rates than those with below-median tumor HER-2 mRNA levels (44% vs. 33%).
The most common adverse events were fatigue (61%), nausea (50%), diarrhea (39%), cough (38%) and anorexia (34%). The most common grade 3 adverse events were thrombocytopenia (13%), fatigue (11%), and increased alanine transaminase and aspartate transaminase levels (9% each).
“T-DM1 and pertuzumab can be combined at full doses with no unexpected toxicities,” the researchers wrote. “The ongoing phase 3 MARIANNE trial, which is evaluating T-DM1 plus pertuzumab versus T-DM1 plus placebo versus trastuzumab plus a taxane in patients with HER-2- positive, progressive or recurrent locally advanced or chemotherapy-naive metastatic breast cancer, will provide a definitive assessment regarding the efficacy and safety of this dual HER-2-targeted combination.”
Disclosure: The researchers report employment or leadership positions with, consultant or advisory roles with, stock ownership in and research funding from Antigen Express, Boehringer Ingelheim, Celgene, Clovis, Entremed, F. Hoffmann-La Roche, Genentech, Genomic Health, GlaxoSmithKline, Imclone, Medivation, Merrimack, Nanostring Technologies, Nektar, Novartis, Pfizer, Roche, Seattle Genetics, Syndax and Taiho.