168P Sacituzumab govitecan (SG) efficacy in patients with metastatic triple-negative breast cancer (mTNBC) by HER2 immunohistochemistry (IHC) status: Findings from the phase III ASCENT study

Hurvitz, S; Bardia, Amit; Punie, Kevin; Kalinsky, Kevin; Cortés, Javier; O’Shaughnessy, Joyce; Carey, L.M.; Rugo, HS; Yoon, Oh Kyu; Pan, Yang; Delaney, Rosemary; Hofsess, Scott; Hodgkins, Paul; Phan, S-C.; Dièras, Véronique

doi:10.1016/j.annonc.2022.03.187

Cited by 18 publications

(16 citation statements)

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“…In the patients with available HER2 IHC, 123/416 patients (29.5%) were HER2low based on archivable tissue, which could be both breast primary or metastatic specimens. 18 Here we provide, to our knowledge, the largest dataset of metastatic patients with TNBC to address the two important questions: what is the frequency of HER2-low in metastatic TNBC and does it influence prognosis? We identified a frequency for HER2-low of 32%dwhich seems to be slightly lower than that reported in early breast cancer (34%-39%) [1][2][3] dand did not find any influence on OS either in univariable (HR 1.00; 95% CI 0.83-1.19; P ¼ 0.969) or in multivariable analysis (HR 0.95; 95% CI 0.79-1.13; P ¼ 0.545).…”

Section: Discussionmentioning

confidence: 99%

Influence of HER2 expression on prognosis in metastatic triple-negative breast cancer—results from an international, multicenter analysis coordinated by the AGMT Study Group

et al. 2023

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Section: Discussionmentioning

confidence: 99%

Influence of HER2 expression on prognosis in metastatic triple-negative breast cancer—results from an international, multicenter analysis coordinated by the AGMT Study Group

et al. 2023

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“…A post hoc analysis of ASCENT trial evaluated the efficacy of SG by HER2 status, reporting a clinical benefit with SG in HER2-0 and HER2-low mTNBC consistent with the overall population. 65 In the HER2-low subgroup treated with SG the mPFS was 6.2 months and mOS was 14 months. Since no direct comparison exists between T-DXd and SG, the choice of which ADC prioritize requires a careful assessment of the available literature and a shared decision-making process with the patient on the basis of the different efficacy and toxicity profile of these two agents.…”

Section: How To Treat Her2-low Mbcmentioning

confidence: 95%

The HER2-low revolution in breast oncology: steps forward and emerging challenges

et al. 2023

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Approximately half of breast cancers (BCs), historically categorized as human epidermal growth factor receptor 2 (HER2)-negative, have low expression of HER2 defined as an immunohistochemical (IHC) score of 1+ or 2+ with negative in situ hybridization. Retrospective evidence suggest that HER2-low BC does not represent a distinct subtype from a biological and prognostic perspective. Nonetheless, it currently constitutes an essential biomarker to guide treatment selection and its introduction has led to reconsidering the binary classification of HER2 status according to which only patients with HER2-positive BC were thought to derive benefit from anti-HER2 therapies. Trastuzumab deruxtecan has recently been approved by the U.S. Food and Drug Administration for the treatment of patients with HER2-low metastatic BC based on the results of the DESTINY-Breast04 phase III trial, and other antibody–drug conjugates (ADCs) targeting HER2 are showing promising results. Treatment paradigms for both triple-negative and hormone receptor-positive BCs exhibiting HER2-low expression are thus rapidly evolving. Given its therapeutic implications, it is essential to accurately recognize the level of HER2 expression, and the development of more sensitive and reliable methods for HER2 testing and scoring is warranted, especially since the minimum threshold of HER2 expression required for T-DXd efficacy is currently under investigation. Given the signs of activity of T-DXd even in patients with HER2-0 (IHC 0) disease, an evolution in the way we define HER2-low is anticipated. Considering the expansion of the therapeutic armamentarium for BC patients, with several ADCs approaching the clinic, research efforts are needed to clarify whether the expression level of targets can enrich for responders to a given ADC as well as to understand mechanisms of resistance with the goal of optimizing the sequencing of ADCs.

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“…The mOS was also longer in the HER2 IHC 0 and HER2‐low arm with SG compared with the PCC (11.3 months vs. 5.9 months; HR, 0.51; p < .001; 14 months vs. 8.7 months; HR, 0.43; p < .001, respectively). The ORR of the HER2 IHC 0 and HER2‐low groups with SG compared with the PCC was 31% vs. 3% and 32% vs. 8%, respectively 36 . This post hoc analysis demonstrates the uniform clinical benefit of SG compared with chemotherapy regardless of the HER2‐low vs. HER2 IHC 0.…”

Section: Introductionmentioning

confidence: 65%

“…36 This post hoc analysis demonstrates the uniform clinical benefit of SG compared with chemotherapy regardless of the HER2-low vs. HER2 IHC 0.Although SG was initially approved for the management of metastatic TNBC, it is important to note that a significant proportionof TNBC cancers are HR-negative HER2-low (26.3%). Hence, this raises the question of the comparative efficacy of SG vs. T-DXd in this subgroup.…”

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confidence: 78%

A review of treatment options in HER2‐low breast cancer and proposed treatment sequencing algorithm

Roy

Kumarasamy

Dhakal

et al. 2023

Cancer

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The expansion of the spectrum of human epidermal growth factor receptor 2 (HER2)‐status to HER2‐low, defined as HER2 expression of 1+ by immunohistochemistry (IHC) or 2+ by IHC without gene amplification, has made a major impact in the field of oncology. The HER2‐low expression has emerged as a targetable biomarker, and anti‐HER2 antibody‐drug conjugate trastuzumab deruxtecan has shown significant survival benefit in pretreated metastatic HER2‐low breast cancer (BC). With these recent data, the treatment algorithm for hormone receptor–positive and triple‐negative BC needs to be reconsidered, as approximately half of these BCs are HER2‐low. Although there are different therapeutic agents for hormone receptor–positive and hormone receptor–negative HER2‐low BCs, there is no consensus regarding the sequencing of these agents. In this article, the treatment options for HER2‐low BC are enumerated and a treatment sequencing algorithm based on the current clinical evidence proposed.

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168P Sacituzumab govitecan (SG) efficacy in patients with metastatic triple-negative breast cancer (mTNBC) by HER2 immunohistochemistry (IHC) status: Findings from the phase III ASCENT study

Cited by 18 publications

References 0 publications

Influence of HER2 expression on prognosis in metastatic triple-negative breast cancer—results from an international, multicenter analysis coordinated by the AGMT Study Group

Influence of HER2 expression on prognosis in metastatic triple-negative breast cancer—results from an international, multicenter analysis coordinated by the AGMT Study Group

The HER2-low revolution in breast oncology: steps forward and emerging challenges

A review of treatment options in HER2‐low breast cancer and proposed treatment sequencing algorithm

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