Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor–Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002)

Hua, Xin; Bi, Xiwen; Zhao, Jianli; Shi, Yanxia; Lin, Ying; Wu, Zhi‐Yong; Zhang, Yuanqi; Zhang, Lehong; Zhang, An-Qing; Huang, Heng; Liu, Xinmei; Xu, Fei; Guo, Ying; Wen, Xiaozhong; Hong, Ruoxi; Jiang, Kuikui; Xue, Cong; An, Xin; Zhong, Yong-Yi; Wang, Shusen; Huang, Jiajia; Yuan, Zhongyu

doi:10.1158/1078-0432.ccr-21-3435

Cited by 36 publications

(32 citation statements)

References 41 publications

(58 reference statements)

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“…However, these results were not adjusted for the type of ERBB2 -targeted therapy or treatment combination . In 2022, a phase III noninferiority trial reached its objective comparing ET with trastuzumab vs CT with trastuzumab. The study did not include the current first-line standard of care with dual- ERBB2 blockade, but it further supported the frequent use of ET observed in the clinical practice given that it also found a significantly higher prevalence of toxic effects in the CT group.…”

Section: Discussionmentioning

confidence: 99%

“…Current European guidelines recommend dual ERBB2 blockade with trastuzumab and pertuzumab (T+P) and CT for ERBB2+ MBC first-line therapy, regardless of HR status, and ET only during maintenance or if the patient is unfit for CT. 4 National Comprehensive Cancer Network (NCCN) guidelines mention ET alone or in combination with ERBB2-targeted therapy as an approach with lower levels of toxic effects for first-line therapy in these patients. 5 Moreover, a 2022 phase III randomized clinical trial 6 found that trastuzumab with ET was noninferior to trastuzumab with CT in patients with HR+/ERBB2+ MBC. Therefore, the role of ET in this setting is not well established, particularly in the context of the current standard first-line therapy that includes dual-ERBB2 blockade.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, a 2022 phase III randomized clinical trial found that trastuzumab with ET was noninferior to trastuzumab with CT in patients with HR+/ ERBB2 + MBC. Therefore, the role of ET in this setting is not well established, particularly in the context of the current standard first-line therapy that includes dual- ERBB2 blockade.…”

Section: Introductionmentioning

confidence: 99%

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Association of Endocrine Therapy for HR+/ERBB2+ Metastatic Breast Cancer With Survival Outcomes

et al. 2022

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ImportanceEvidence suggests that patients with human epidermal growth factor receptor 2–positive (ERBB2+ [formerly HER2+]) metastatic breast cancer (MBC) have different clinical characteristics and outcomes according to their hormone receptor (HR) status. The place of endocrine therapy (ET) for patients with HR+/ERBB2+ is still not clearly defined in this setting.ObjectiveTo evaluate the association of HR status and first-line inclusion of ET with outcomes among patients with ERBB2+ MBC.Design, Setting, and ParticipantsThis cohort study was an analysis of clinical data from the French clinical Epidemiological Strategy and Medical Economics (ESME) cohort, including patients with MBC who started treatment between 2008 and 2017. The last date of follow-up was June 18, 2020. Data were analyzed from May 2021 to May 2022.ExposuresPatients were treated with first-line ERBB2-targeted therapy and either chemotherapy (CT) with or without ET or ET alone. For the study of the association of maintenance ET with outcomes, we included patients treated with first-line ERBB2-targeted therapy with CT and with or without maintenance ET.Main Outcomes and MeasuresMedian overall survival (OS) and median first-line progression-free survival (PFS) were reported using the Kaplan-Meier method. Cox proportional hazards models and a propensity score were constructed to report and adjust for prognostic factors. Multivariable analysis included age at MBC, time to MBC, number of metastatic sites, type of metastases, and Eastern Cooperative Oncology Group performance status.ResultsAmong 4145 women with ERBB2+ MBC, 2696 patients had HR+ (median [IQR] age, 58.0 [47.0-67.0] years) and 1449 patients had HR– (56.0 [47.0-64.0] years) tumors. The median OS for patients with HR+ vs HR− tumors was 55.9 months (95% CI, 53.7-59.4 months) vs 42.0 months (95% CI, 38.8-45.2 months), confirmed in multivariable analysis (hazard ratio, 1.40; 95% CI, 1.26-1.56; P &lt; .001). The median PFS for patients with HR+ vs HR− tumors was 12.2 months (95% CI, 11.5-12.9 months) vs 9.8 months (95% CI, 9.2-11.0 months; P = .01), and the HR was 1.15 (95% CI, 1.06-1.26; P &lt; .001). In multivariable analysis, no significant difference was found in OS or PFS for 1520 patients treated with ERBB2-targeted therapy with CT and with or without ET vs 203 patients receiving ERBB2-targeted therapy with ET, regardless of type of ERBB2-targeted therapy (trastuzumab or trastuzumab with pertuzumab). This result was confirmed by matching patients using a propensity score. Using the time-dependent ET variable among patients with ERBB2-targeted therapy with CT, those with maintenance ET had significantly better PFS (hazard ratio, 0.70; 95% CI, 0.60-0.82; P &lt; .001) and OS (hazard ratio, 0.47; 95% CI, 0.39-0.57; P &lt; .001).Conclusions and RelevanceThese results suggest that ET-containing first-line regimens may be associated with benefits among a subgroup of patients with HR+/ERBB2+ MBC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association of Endocrine Therapy for HR+/ERBB2+ Metastatic Breast Cancer With Survival Outcomes

et al. 2022

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“…The recommended first‐line therapy is currently dual HER2 blockade with trastuzumab and pertuzumab in combination with chemotherapy (preferably taxanes) [ 204 , 205 ]. Patients with HR‐positive and HER2‐positive tumors have the alternative of receiving ET in combination with HER2‐targeted therapy [ 206 , 207 , 208 ]. The second line options include trastuzumab deruxtecan (T‐DXd), T‐DM1, and pyrotinib (approved in China).…”

Section: Mbcmentioning

confidence: 99%

Breast cancer: an up‐to‐date review and future perspectives

Hong

2022

Cancer Communications

129

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Breast cancer is the most common cancer worldwide. The occurrence of breast cancer is associated with many risk factors, including genetic and hereditary predisposition. Breast cancers are highly heterogeneous. Treatment strategies for breast cancer vary by molecular features, including activation of human epidermal growth factor receptor 2 (HER2), hormonal receptors (estrogen receptor [ER] and progesterone receptor [PR]), gene mutations (e.g., mutations of breast cancer 1/2 [BRCA1/2] and phosphatidylinositol‐4,5‐bisphosphate 3‐kinase catalytic subunit alpha [PIK3CA]) and markers of the immune microenvironment (e.g., tumor‐infiltrating lymphocyte [TIL] and programmed death‐ligand 1 [PD‐L1]). Early‐stage breast cancer is considered curable, for which local‐regional therapies (surgery and radiotherapy) are the cornerstone, with systemic therapy given before or after surgery when necessary. Preoperative or neoadjuvant therapy, including targeted drugs or immune checkpoint inhibitors, has become the standard of care for most early‐stage HER2‐positive and triple‐negative breast cancer, followed by risk‐adapted post‐surgical strategies. For ER‐positive early breast cancer, endocrine therapy for 5‐10 years is essential. Advanced breast cancer with distant metastases is currently considered incurable. Systemic therapies in this setting include endocrine therapy with targeted agents, such as CDK4/6 inhibitors and phosphoinositide 3‐kinase (PI3K) inhibitors for hormone receptor‐positive disease, anti‐HER2 targeted therapy for HER2‐positive disease, poly(ADP‐ribose) polymerase inhibitors for BRCA1/2 mutation carriers and immunotherapy currently for part of triple‐negative disease. Innovation technologies of precision medicine may guide individualized treatment escalation or de‐escalation in the future. In this review, we summarized the latest scientific information and discussed the future perspectives on breast cancer.

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“…The HER2+ breast cancer subtype is defined by assessment of HER2 expression by immunohistochemistry (score 3+ or 2+ with positive ISH), and the standard of care treatment is trastuzumab, a monoclonal antibody directed to the HER2 molecule [ 12 ], which is administered based on the results of HER2 expression. In the case of HER2+ breast cancer with positive hormone receptors (luminal B), endocrine therapy is incorporated into the trastuzumab and chemotherapy administration [ 13 , 14 ]. There are several prognostic biomarkers for HER2+ breast cancer, but no predictive biomarkers to determine which HER2-targeted therapy will be more effective for the patient.…”

Section: Introductionmentioning

confidence: 99%

Emerging Targeted Therapies for HER2-Positive Breast Cancer

Mercogliano

Bruni

Mauro

et al. 2023

Cancers

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Breast cancer is the most common cancer in women and the leading cause of death. HER2 overexpression is found in approximately 20% of breast cancers and is associated with a poor prognosis and a shorter overall survival. Tratuzumab, a monoclonal antibody directed against the HER2 receptor, is the standard of care treatment. However, a third of the patients do not respond to therapy. Given the high rate of resistance, other HER2-targeted strategies have been developed, including monoclonal antibodies such as pertuzumab and margetuximab, trastuzumab-based antibody drug conjugates such as trastuzumab-emtansine (T-DM1) and trastuzumab-deruxtecan (T-DXd), and tyrosine kinase inhibitors like lapatinib and tucatinib, among others. Moreover, T-DXd has proven to be of use in the HER2-low subtype, which suggests that other HER2-targeted therapies could be successful in this recently defined new breast cancer subclassification. When patients progress to multiple strategies, there are several HER2-targeted therapies available; however, treatment options are limited, and the potential combination with other drugs, immune checkpoint inhibitors, CAR-T cells, CAR-NK, CAR-M, and vaccines is an interesting and appealing field that is still in development. In this review, we will discuss the highlights and pitfalls of the different HER2-targeted therapies and potential combinations to overcome metastatic disease and resistance to therapy.

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Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor–Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002)

Cited by 36 publications

References 41 publications

Association of Endocrine Therapy for HR+/ERBB2+ Metastatic Breast Cancer With Survival Outcomes

Association of Endocrine Therapy for HR+/ERBB2+ Metastatic Breast Cancer With Survival Outcomes

Breast cancer: an up‐to‐date review and future perspectives

Emerging Targeted Therapies for HER2-Positive Breast Cancer

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