Margetuximab in HER2-positive metastatic breast cancer

Figures & data

Figure 1. Mechanism of action of anti-HER2 mAb margetuximab and differences between trastuzumab and margetuximab.

(A) Margetuximab mediates antiproliferative (Fc-independent) and immune activation (Fc-dependent) effects. (B) The Fc engineering of margetuximab alters Fcγ receptor affinities. The red X in panel A (on the left side) indicates inhibition.

ADCC: Antibody-dependent cellular cytotoxicity; ADCP: Antibody-dependent cellular phagocytosis; CD: Cluster of differentiation; Fab: Fragment antigen-binding; Fc: Fragment crystallizable; FcγR: Fragment crystallizable gamma receptor; IgG: Immunoglobin G; M: Margetuximab; mAb: Monoclonal antibody; MHC II: Major histocompatibility complex class II; NK: Natural killer; T: Trastuzumab; TAA: Tumor-associated antigen.

(A) reproduced from [26], with permission from BMJ Publishing Group Ltd.

Figure 2. SOPHIA progression-free survival (A) and overall survival (B) in the intent-to-treat population.

HR: Hazard ratio; ITT: Intent-to-treat; mo: Month; OS: Overall survival; PFS: Progression-free survival.

(A) Reproduced from [37], with permission from Rugo HS. (B) Reproduced from [19], https://ascopubs.org/journal/jco/.

Table 1. Prespecified^† exploratory progression-free survival and overall survival subgroup analyses by chemotherapy backbone.

All patients or investigator-selected chemotherapy backbone	No. Events/total^‡		Median PFS (95% CI), months^‡		Hazard ratio by unstratified Cox model (95% CI)^‡	Nominal unstratified log-rank p-value^‡
	Margetuximab + chemotherapy	Trastuzumab + chemotherapy	Margetuximab + chemotherapy	Trastuzumab + chemotherapy
All patients (N = 536)	130/266	135/270	5.8 (5.52–6.97)	4.9 (4.17–5.59)	0.78 (0.61–0.99)	0.044
Capecitabine (n = 143)	29/71	37/72	8.3 (5.55–11.50)	5.5 (4.17–8.28)	0.77 (0.47–1.29)	0.302
Eribulin (n = 136)	35/66	39/70	6.0 (3.81–8.05)	4.2 (3.38–5.55)	0.66 (0.42–1.05)	0.080
Gemcitabine (n = 66)	15/33	17/33	5.4 (4.07–11.01)	3.5 (1.45–7.16)	0.58 (0.29–1.18)	0.128
Vinorelbine (n = 191)	51/96	42/95	5.6 (4.24–6.97)	5.1 (3.42–6.67)	0.90 (0.60–1.35)	0.606
All patients or investigator-selected chemotherapy backbone	No. Events/total ^§		Median OS (95% CI), months ^§		Hazard ratio by unstratified Cox model (95% CI) ^§	Nominal unstratified log-rank p-value ^§
	Margetuximab + chemotherapy	Trastuzumab + chemotherapy	Margetuximab + chemotherapy	Trastuzumab + chemotherapy
All patients (N = 536)	194/266	191/270	21.6 (18.89–25.07)	21.9 (18.69–24.18)	0.96 (0.79–1.18)	0.716
Capecitabine (n = 143)	52/71	51/72	23.6 (15.05–32.76)	23.5 (19.19–31.24)	1.05 (0.72–1.55)	0.794
Eribulin (n = 136)	51/66	49/70	20.7 (18.37–25.49)	16.7 (14.39–27.24)	1.01 (0.68–1.49)	0.981
Gemcitabine (n = 66)	23/33	22/33	21.3 (12.02–29.44)	22.6 (18.00–31.90)	0.98 (0.54–1.75)	0.934
Vinorelbine (n = 191)	68/96	69/95	21.5 (17.48–30.62)	21.0 (16.66–24.67)	0.88 (0.63–1.23)	0.446

† Non-α allocating analysis.

‡ Oct 2018 cut-off.

§ Jun 2021 cut-off.

OS: Overall survival; PFS: Progression-free survival.

The upper part of the table is reproduced from [37], with permission from Rugo HS. The lower part of the table reproduced from [19], https://ascopubs.org/journal/jco/.

Figure 3. SOPHIA overall survival analysis, per CD16A genotype by treatment group.

(A) Kaplan–Meier estimates of OS by treatment group in CD16A-158F carriers (FF or FV), (B) CD16A-158FF homozygotes, (C) CD16A-158FV heterozygotes and (D) CD16A-158VV homozygotes.

HR: Hazard ratio; OS: Overall survival.

Reproduced from [19], https://ascopubs.org/journal/jco/.

Figure 4. Overall landscape of treatments for HER2-positive metastatic breast cancer in the first-, second- and third-line settings.

CTX: Chemotherapy; mAb: Monoclonal antibody; TKI: Tyrosine kinase inhibitor.

Musolino A , GradisharWJ, RugoHSet al. Role of Fcγ receptors in HER2-targeted breast cancer therapy. J. Immunother. Cancer10(1), e003171 (2022).

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Rugo HS , ImSA, CardosoFet al. Efficacy of margetuximab vs trastuzumab in patients with pretreated ERBB2-positive advanced breast cancer: a phase 3 randomized clinical trial. JAMA Oncol.7(4), 573–584 (2021).

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Rugo HS , ImS-A, CardosoFet 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. J. Clin. Oncol.41(2), 198–205 (2023).

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