Margetuximab vs Trastuzumab in Pretreated ERBB2-Positive Advanced Breast Cancer

The best way to treat ERRB2 (previously HER2)-positive advanced breast cancer (ABC) in the later stages of treatment is still unclear. Margetuximab, like trastuzumab, is a chimeric antibody, but its modified Fc region stimulates the immune system more effectively. This study aims to evaluate the clinical effectiveness of margetuximab against trastuzumab in patients with pretreated ERBB2-positive ABC. From August 26, 2015, to October 10, 2018, 536 patients were enrolled in the SOPHIA phase 3 randomized open-label trial of margetuximab with chemotherapy versus trastuzumab plus chemotherapy at 166 sites in 17 countries. Metastatic disease progression after 2 or more lines of anti-ERBB2 therapy were required for eligibility. From February 2019 to October 2019, data were evaluated. Before 1:1 randomization to margetuximab (15 mg/kg) or trastuzumab (6 mg/kg; loading dose, 8 mg/kg), both treatments were administered in 3-week cycles. The number of metastatic locations (2, >2), number of lines of therapy, and type of chemotherapy used were included as stratification criteria. As determined by central blinded analysis, PFS was the first primary endpoint, followed by OS. PFS received all, and OS came in second. The secondary end goals were the investigator-assessed PFS and objective response rate by the central blinded analysis.

A total of 536 patients were split evenly between margetuximab (n = 266) and trastuzumab (n = 270). There were 266 women in the margetuximab group and 267 women in the trastuzumab group, with a median age of 56 (27-86). Each group had an equal number of members. Pertuzumab was given to only one patient, while ado-trastuzumab emtansine was given to 489 (91.2%). As of October 10, 2018, margetuximab had a 24% relative risk decrease compared to trastuzumab in terms of primary PFS (hazard ratio [HR], 0.76; 95% CI, 0.59-0.98; P =.03; median, 5.8 [95% CI, 5.5-7.0] months vs. 4.9 [95% CI, 4.2-5.6] months). As of the second planned interim analysis of 270 deaths, the median overall survival (OS) with margetuximab was 21.6 months compared to 19.8 months with trastuzumab (HR, 0.89; 95% CI, 0.69-1.13; P =.33; September 10, 2019), and the investigator-assessed progression-free survival (PFS) showed a 29% relative risk reduction favoring margetuximab (HR, 0.71; 95% CI, 0. Two-year objective response rates with trastuzumab and margetuximab were 22% and 16%, respectively (P = .06 and P < .001 on October 10, 2018, and September 10, 2019, respectively). Among infusion-related adverse events, margetuximab had a greater incidence (35 [13.3%] vs. 9 [3.4%]); however, overall safety was comparable. After progression on 2 or more prior anti-ERBB2 medications, ERBB2-positive ABC patients in this randomized phase 3 clinical trial showed a statistically significant increase in PFS when treated with margetuximab plus chemotherapy.

Source:https://pubmed.ncbi.nlm.nih.gov/33480963/

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

Rugo HS, Im SA, Cardoso F, Cortés J, Curigliano G, Musolino A, Pegram MD, Wright GS, Saura C, Escrivá-de-Romaní S, De Laurentiis M, Levy C, Brown-Glaberman U, Ferrero JM, de Boer M, Kim SB, Petráková K, Yardley DA, Freedman O, Jakobsen EH, Kaufman B, Yerushalmi R, Fasching PA, Nordstrom JL, Bonvini E, Koenig S, Edlich S, Hong S, Rock EP, Gradishar WJ; SOPHIA Study Group. Efficacy of Margetuximab vs. Trastuzumab in Patients With Pretreated ERBB2-Positive Advanced Breast Cancer: A Phase 3 Randomized Clinical Trial. JAMA Oncol. 2021 Apr 1;7(4):573-584. doi: 10.1001/jamaoncol.2020.7932. PMID: 33480963; PMCID: PMC7823434.