medwireNews: The final overall survival (OS) analysis of the SOPHIA study has shown no significant benefit of adding margetuximab instead of trastuzumab to chemotherapy in previously treated patients with HER2-positive (HER2+), advanced breast cancer.
However, the investigators point out in the clinical trial update published in the Journal of Clinical Oncology that exploratory analyses suggest a difference in OS results by Fcγ receptor genotype.
The randomized phase 3 trial – comprising 536 patients who had received two or more prior HER2-directed therapies, at least one of which was in the metastatic setting – previously showed a significant 24% reduction in the risk for progression or death with the use of margetuximab 15 mg/kg versus trastuzumab 6 mg/kg every 3 weeks alongside physician’s choice of single-agent chemotherapy.
This progression-free survival (PFS) benefit failed to translate into an OS gain, however, with the current analysis, conducted at a median follow-up of 20.2 months, showing no significant difference between patients who received margetuximab and those given trastuzumab. The median OS durations were a comparable 21.6 and 21.9 months, respectively.
In prespecified exploratory analyses of OS by Fcγ receptor genotype in 506 participants with available genotyping data, the use of margetuximab rather than trastuzumab appeared to be associated with an OS improvement among CD16A-158FF homozygotes but not CD16A-158FV heterozygotes, at medians of 23.6 versus 19.2 months and 21.3 versus 22.0 months, respectively.
The analyses also pointed to a potential OS benefit in favor of trastuzumab among participants carrying the homozygous CD16A-158VV allele, such that the median OS duration was 22.0 months with margetuximab and 31.1 months with trastuzumab.
“Studies of margetuximab in patients with HER2+ [breast cancer] with different CD16A allelic variants are warranted, including MARGOT […], a randomized phase 2, neoadjuvant investigator-initiated study on the efficacy of margetuximab versus trastuzumab (both plus pertuzumab and paclitaxel) in patients with stage II–III HER2+ [breast cancer] carrying the CD16A-158F low-affinity allele,” write the researchers.
Hope Rugo (University of California San Francisco Helen Diller Family Comprehensive Cancer Center, USA) and fellow SOPHIA investigators also reported updated safety data, noting that the findings for margetuximab plus chemotherapy “confirmed an acceptable profile comparable with trastuzumab plus chemotherapy, similar to previous reports and consistent with the US Food and Drug Administration–approved label for margetuximab.”
Specifically, adverse events of grade 3 or worse occurred in a comparable 55.3% of margetuximab- and 53.0% of trastuzumab-treated patients. The most common events of this severity in the margetuximab and trastuzumab groups were neutropenia (20.5 and 12.4%, respectively) and neutrophil count decrease (8.7 and 10.5%).
An identical 3.8% of patients in both treatment arms discontinued from the study due to toxicity, and there were four deaths due to adverse events in the margetuximab group and two in the trastuzumab group, although none were considered related to the study treatments.
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