J Clin Oncol: Long-term efficacy of Margetuximab-cmkb in the treatment of metastatic HER2-positive breast cancer

Margetuximab-cmkb (magmodoximab) is an Fc-engineered anti-human epidermal growth factor receptor 2 (anti-HER2) immunoglobulin G monoclonal antibody that targets the same epitope as trastuzumab and has similar antiproliferative effects
。 Compared to trastuzumab, Margetuximab is designed to increase the binding affinity of the (in vitro) activated Fcγ receptor (Fcγr) CD16A (Fcγ riiia) and reduce the binding affinity
of inhibitory Fcγr CD32B (Fcγ riib).

The SOPHIA study, a randomized, open-label, pivotal Phase 3 clinical trial of Margetuximab in the treatment of breast cancer, showed that Margetuximab+ chemotherapy significantly reduced the risk of disease progression or death by 24%
compared with trastuzumab + chemotherapy in patients with metastatic HER2-positive breast cancer who had previously received multiple anti-HER2 regimens.

This article reports the final analysis of the SOPHIA study
.

In this trial, 536 patients were randomized to Margetuximab (n=266) or trastuzumab (n=270) to receive Margetuximab (15 mg/kg for 3 weeks) + chemotherapy or trastuzumab (6 mg/kg for 3 weeks) + chemotherapy
.
The primary endpoints were progression-free survival and overall survival
.
A final overall survival analysis
was triggered after 385 predetermined events.

OS rates in both groups of the general population

By the date of analysis, there had been a median follow-up of 20.
2 months, with a total of 385 deaths
.
The median OS in the Margetuximab and trastuzumab groups was 21.
6 months and 21.
9 months, respectively (HR 0.
95, p=0.
620).

。 Exploratory analysis of CD16A genotypes showed that Margetuximab-treated OS in patients with CD16A-158FF was superior to trastuzumab (median OS 23.
6 vs 19.
2 months; HR 0.
72), patients with CD16A-158VV may have better OS treated with trastuzumab than Margetuximab (median OS 31.
1 vs 22.
0 months; HR 1.
77）
。 The safety profile of Margetuximab is comparable
to that of trastuzumab.
The final overall OS analysis did not demonstrate that Margetuximab was superior to trastuzumab
.

OS rate in two groups of CD16A-158FF patients

OS rate in two groups of CD16A-158VV patients

Taken together, the results of this study suggest that the Margetuximab study is necessary in human epidermal growth factor receptor 2-positive breast cancer patients with different CD16A allele variants
.

Original source:

Hope S.
Rugo, et al.
Margetuximab Versus Trastuzumab in Patients With Previously Treated HER2-Positive Advanced Breast Cancer (SOPHIA): Final Overall Survival Results From a Randomized Phase 3 Trial.
Journal of Clinical Oncology.
November 4, 2022.
https://ascopubs.
org/doi/full/10.
1200/JCO.
21.
02937