Margetuximab-cmkb Versus Trastuzumab in ERBB2-Positive Advanced Breast Cancer
Posted: Thursday, March 11, 2021
William J. Gradishar, MD, of Northwestern University, Chicago, and colleagues conducted a phase III study to compare the efficacy of chemotherapy plus two different monoclonal antibodies: a median of six cycles of margetuximab-cmkb plus chemotherapy versus five cycles of trastuzumab plus chemotherapy. In patients with ERBB2-positive advanced breast cancer, the investigators demonstrated a head-to-head advantage for margetuximab over trastuzumab, with acceptable safety and a statistically significant improvement in progression-free survival. Their work was published in JAMA Oncology.
A total of 536 patients with pretreated ERBB2-positive advanced breast cancer were enrolled in a phase III randomized open-label trial. Individuals were stratified depending on metastatic sites, lines of therapy, and chemotherapy choice. They were randomly assigned (1:1) to receive either the margetuximab arm or the trastuzumab arm, and the median patient ages were 55 and 56, respectively.
The margetuximab combination improved primary progression-free survival over the trastuzumab combination, with a 24% relative risk reduction (P = .03), with a median of 5.8 months versus 4.9 months. After a second planned interim analysis of 270 deaths, the median overall survival with margetuximab was 21.6 months versus 19.8 months with trastuzumab (P = .33). Investigator-assessed progression-free survival yielded a 29% relative risk reduction with margetuximab (P < .001).
Grade 3 or greater adverse events occurred in at least 5% of all study patients. Adverse events of note included infusion-related reactions and left ventricular dysfunction. Grade 3 infusion-related reactions were reported in 1.5% of patients in the margetuximab arm. Grade 3 left ventricular dysfunction occurred in 1.1% of margetuximab recipients and 0.4% of trastuzumab recipients.
The investigators acknowledged that their study had several limitations. First, the primary endpoint did not allocate significance to the CD16A analysis performed in earlier phases. Second, patients with active brain metastases were omitted.
Disclosure: For full disclosures of study authors, visit jamanetwork.com.
