Examining the Potential of Margetuximab in the Treatment of HER2+ Metastatic Breast Cancer

In clinical trials, it is common to observe the maturation of multiple endpoints at varying intervals. The preliminary findings, usually centered on the primary endpoint, may be released before significant planned co-primary or secondary analyses are completed. The Clinical Trial Updates offer a chance to distribute supplementary findings from investigations, which have already been published in JCO or other sources, and have already achieved their primary objective. The updated safety and overall survival (OS) findings of SOPHIA (ClinicalTrials.gov identifier: NCT02492711), a clinical trial comparing the efficacy of margetuximab versus trastuzumab, both in combination with chemotherapy, among patients with advanced breast cancer previously treated for human epidermal growth factor receptor 2-positive, have been reported. In the intention-to-treat population, a total of 536 patients were randomly allocated to receive either margetuximab (15 mg/kg intravenously once every 3 weeks; n = 266) in combination with chemotherapy or trastuzumab (6 mg/kg intravenously once every 3 weeks following a loading dose of 8 mg/kg; n = 270) in combination with chemotherapy.

The primary endpoints encompass progression-free survival, which has been previously documented, and overall survival. 385 pre-determined occurrences prompted the initiation of the final operating system analysis. The study found that the median overall survival (OS) for patients treated with margetuximab was 21.6 months (95% CI, 18.89 to 25.07), while those treated with trastuzumab had a median OS of 21.9 months (95% CI, 18.69 to 24.18). The hazard ratio (HR) was 0.95 (95% CI, 0.77 to 1.17; P = .620). An exploratory analysis of CD16A genotyping was conducted, which revealed a potential increase in overall survival for margetuximab in CD16A-158FF patients compared to trastuzumab (with a median overall survival of 23.6 months versus 19.2 months, respectively, and a hazard ratio of 0.72 and a 95% confidence interval of 0.52 to 1.00). Additionally, there was a possible improvement in overall survival for trastuzumab in CD16A-158VV patients compared to margetuximab (with a median overall survival of 31.1 months versus 22.0 months, respectively, and a hazard ratio of 1.77 and a 95% confidence interval of 1.01 to 3.12).

The safety profile of margetuximab was comparable to that of trastuzumab. The conclusive comprehensive analysis of the operating system did not reveal any superiority of margetuximab over trastuzumab. Further investigation is necessary to evaluate the efficacy of Margetuximab in individuals with human epidermal growth factor receptor 2-positive breast cancer who possess varying CD16A allelic variants.

Source: https://pubmed.ncbi.nlm.nih.gov/36332179/

Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT02492711

Rugo HS, Im SA, Cardoso F, Cortes J, Curigliano G, Musolino A, Pegram MD, Bachelot T, Wright GS, Saura C, Escrivá-de-Romaní S, De Laurentiis M, Schwartz GN, Pluard TJ, Ricci F, Gwin WR 3rd, Levy C, Brown-Glaberman U, Ferrero JM, de Boer M, Kim SB, Petráková K, Yardley DA, Freedman O, Jakobsen EH, Gal-Yam EN, Yerushalmi R, Fasching PA, Kaufman PA, Ashley EJ, Perez-Olle R, Hong S, Rosales MK, Gradishar WJ; SOPHIA Study Group. Margetuximab Versus Trastuzumab in Patients With Previously Treated HER2-Positive Advanced Breast Cancer (SOPHIA): Final Overall Survival Results From a Randomized Phase 3 Trial. J Clin Oncol. 2023 Jan 10;41(2):198-205. doi: 10.1200/JCO.21.02937. Epub 2022 Nov 4. PMID: 36332179; PMCID: PMC9839304.