Pyrotinib plus capecitabine versus lapatinib plus capecitabine for the treatment of HER2-positive metastatic breast cancer (PHOEBE): a multicentre, open-label, randomised, controlled, phase 3 trial

Xu, Binghe; Yan, Min; Ma, Fei; Hu, Xichun; Feng, Jifeng; Ouyang, Qi; Tong, Zhongsheng; Li, Huiping; Zhang, Qingyuan; Sun, Tao; Wang, Xian; Yin, Yongmei; Cheng, Ying; Li, Wei; Gu, Yuanting; Chen, Qianjun; Liu, Jinping; Cheng, Jing; Geng, Cuizhi; Qin, Shukui; Wang, Shusen; Lu, Jinsong; Shen, Kunwei; Liu, Qiang; Wang, Xiaojia; Wang, Hong; Luo, Ting; Yang, Jin; Wu, Yudong; Yu, Zhiyong; Zhu, Xiaoyu; Chen, Chunxia; Zou, Jianjun; Investigators, Phoebe

doi:10.1016/s1470-2045(20)30702-6

Cited by 207 publications

(235 citation statements)

References 25 publications

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“…In EMILIA study, thrombocytopenia (12.9%), elevated serum concentrations of aspartate aminotransferase (4.3%), and alanine aminotransferase (2.9%) were the most commonly reported grade ≥3 AEs of T-DM1 (9). Nevertheless, the most frequent grade ≥3 AEs of Pyr-Cap were diarrhea (30.8%) and hand-foot syndrome (15.7%) in the PHENIX study, and diarrhea (30.6%) and hand-foot syndrome (16.4%) in the PHOEBE study (37,38,46). Frequent occurrence of diarrhea could be the reason why Pyr-Cap ranked in the highest of grade ≥3 AEs in this network meta-analysis.…”

Section: Discussionmentioning

confidence: 96%

“…It directly acts on the intracellular tyrosine kinase region and blocks the downstream pathways of HER family homo/heterodimers (20). Therefore, Pyr may be still effective for HER2+ MBC patients who progressed on Tra (45) (38,46). 134 and 132 HER2+ MBC patients pre-treated with Tra and a taxane were randomly assigned to receive Pyr-Cap and Lap-Cap, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…Frequent occurrence of diarrhea could be the reason why Pyr-Cap ranked in the highest of grade ≥3 AEs in this network meta-analysis. Despite the high incidence, the grade ≥3 diarrhea caused by Pyr-Cap is reversible and occurs in the early stage of treatment with a short duration, barely leading to the discontinuation of treatment (37,38,46). Therefore, the safety of Pyr could be considered acceptable.…”

Section: Discussionmentioning

confidence: 99%

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Efficacy and Safety of Pyrotinib Versus T-DM1 in HER2+ Metastatic Breast Cancer Patients Pre-Treated With Trastuzumab and a Taxane: A Bayesian Network Meta-Analysis

et al. 2021

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PurposeTo compare the efficacy and safety between pyrotinib (Pyr) and trastuzumab emtansine (T-DM1) in pre-treated human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) patients.MethodsA comprehensive literature search of the PubMed, EMBASE, and Web of Science was performed in August 2020. Randomized clinical trials comparing the efficacy and safety between different anti-HER2 regimens in patients pre-treated with trastuzumab (Tra) and a taxane in metastatic settings (≤second-line treatment) were included. A fixed effects network meta-analysis based on the Bayesian inferential framework was conducted for progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and grade ≥3 adverse events (AEs). Values of surface under cumulative ranking probability curve (SUCRA) were calculated to offer a ranking of all regimens.ResultsTwelve studies with 4,353 subjects were identified. Nine regimens were included into the network: T-DM1, lapatinib-capecitabine (Lap-Cap), Tra-Cap, Cap, neratinib (Ner), pertuzumab (Per)-Tra-Cap, Pyr-Cap, atezolizumab (Ate)-T-DM1, and Ner-Cap. For PFS, Pyr-Cap was more favorable than T-DM1 (hazard ratio, 95% confidence interval: 0.77, 0.70–0.86), Lap-Cap (0.64, 0.59–0.69), Tra-Cap (0.63, 0.56–0.70), Cap (0.50, 0.45–0.56), Ner (0.59, 0.51–0.69), Per-Tra-Cap (0.68, 0.59–0.79), and Ner-Cap (0.72, 0.64–0.81). For OS, Pyr-Cap showed further improvement than Lap-Cap (hazard ratio, 95% confidence interval: 0.71, 0.52–0.99), Cap (0.68, 0.49–0.96), and Ner (0.65, 0.45–0.94). For ORR, Pyr-Cap was significantly superior than Cap (odds ratio, 95% confidence interval: 7.87, 1.22–56.51). No significant difference was observed in grade ≥3 AEs among all the regimens. Pyr-Cap ranked in the highest in PFS, OS, ORR, and grade ≥3 AEs (SUCRA = 99.4, 89.7, 86.4, and 89.3%).ConclusionsThese results indicate that Pyr may be more effective than T-DM1 in HER2+ MBC patients pre-treated with Tra and a taxane. However, it may be associated with more grade ≥3 AEs.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Efficacy and Safety of Pyrotinib Versus T-DM1 in HER2+ Metastatic Breast Cancer Patients Pre-Treated With Trastuzumab and a Taxane: A Bayesian Network Meta-Analysis

et al. 2021

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“…Patients (n=267) were required to have received prior trastuzumab and taxane, but prior pertuzumab was not obligatory. 104 At the interim analysis, the pyrotinib arm was associated with a significantly longer PFS of 12.5 vs 6.8 months (HR 0.39, 95% CI: 0.27–0.56, P <0.0001) with the OS data still immature. 104 Toxicity remained an issue, with G3-4 diarrhoea affecting a worrying 30.6% of patients randomised to the pyrotinib arm.…”

Section: Scope Of This Reviewmentioning

confidence: 98%

“… 104 At the interim analysis, the pyrotinib arm was associated with a significantly longer PFS of 12.5 vs 6.8 months (HR 0.39, 95% CI: 0.27–0.56, P <0.0001) with the OS data still immature. 104 Toxicity remained an issue, with G3-4 diarrhoea affecting a worrying 30.6% of patients randomised to the pyrotinib arm. 104 While these data are evocative, the utility of this drug cannot be assured until further trials assess its efficacy after pertuzumab and T-DM1 and measures are in place to abrogate its excessive toxicity.…”

Section: Scope Of This Reviewmentioning

confidence: 98%

Treating Advanced Unresectable or Metastatic HER2-Positive Breast Cancer: A Spotlight on Tucatinib

Ulrich

Okines

2021

BCTT

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The management of HER2 positive breast cancer has been transformed by the development of targeted therapies. Dual blockade with the monoclonal antibodies, trastuzumab and pertuzumab, added to first-line taxane chemotherapy and second-line therapy with the antibody-drug conjugate, T-DM1, are internationally agreed standards of care for advanced HER2 positive breast cancer, where available. However, until recently, options for patients for third-line therapy and beyond were of modest efficacy or limited by toxicity. In 2019, the results of trials of two exciting new agents for this space were presented. A third-generation HER2 tyrosine kinase inhibitor, tucatinib, combines the efficacy of the second-generation drug, neratinib, with a more manageable toxicity profile and has become a new standard of care after T-DM1, in combination with capecitabine and trastuzumab. The antibody-drug conjugate, trastuzumab deruxtecan, demonstrated remarkable efficacy in heavily pre-treated patients and received accelerated approval in the United States, whilst confirmatory Phase 3 trials are completed. This review will discuss the available data for the post-T-DM1 setting, focusing on tyrosine kinase inhibitors including tucatinib.

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A Multifunctional Bimetallic Nanoplatform for Synergic Local Hyperthermia and Chemotherapy Targeting HER2‐Positive Breast Cancer

Zhao,

Chang,

Tong

et al. 2024

Advanced Science

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Anti‐HER2 (human epidermal growth factor receptor 2) therapies significantly increase the overall survival of patients with HER2‐positive breast cancer. Unfortunately, a large fraction of patients may develop primary or acquired resistance. Further, a multidrug combination used to prevent this in the clinic places a significant burden on patients. To address this issue, this work develops a nanotherapeutic platform that incorporates bimetallic gold‐silver hollow nanoshells (AuAg HNSs) with exceptional near‐infrared (NIR) absorption capability, the small‐molecule tyrosine kinase inhibitor pyrotinib (PYR), and Herceptin (HCT). This platform realizes targeted delivery of multiple therapeutic effects, including chemo‐and photothermal activities, oxidative stress, and immune response. In vitro assays reveal that the HCT‐modified nanoparticles exhibit specific recognition ability and effective internalization by cells. The released PYR inhibit cell proliferation by downregulating HER2 and its associated pathways. NIR laser application induces a photothermal effect and tumor cell apoptosis, whereas an intracellular reactive oxygen species burst amplifies oxidative stress and triggers cancer cell ferroptosis. Importantly, this multimodal therapy also promotes the upregulation of genes related to TNF and NF‐κB signaling pathways, enhancing immune activation and immunogenic cell death. In vivo studies confirm a significant reduction in tumor volume after treatment, substantiating the potential effectiveness of these nanocarriers.

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Pyrotinib plus capecitabine versus lapatinib plus capecitabine for the treatment of HER2-positive metastatic breast cancer (PHOEBE): a multicentre, open-label, randomised, controlled, phase 3 trial

Cited by 207 publications

References 25 publications

Efficacy and Safety of Pyrotinib Versus T-DM1 in HER2+ Metastatic Breast Cancer Patients Pre-Treated With Trastuzumab and a Taxane: A Bayesian Network Meta-Analysis

Efficacy and Safety of Pyrotinib Versus T-DM1 in HER2+ Metastatic Breast Cancer Patients Pre-Treated With Trastuzumab and a Taxane: A Bayesian Network Meta-Analysis

Treating Advanced Unresectable or Metastatic HER2-Positive Breast Cancer: A Spotlight on Tucatinib

A Multifunctional Bimetallic Nanoplatform for Synergic Local Hyperthermia and Chemotherapy Targeting HER2‐Positive Breast Cancer

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