First-line pyrotinib in advanced HER2-mutant non-small-cell lung cancer: a patient-centric phase 2 trial

Liu, Si‐Yang Maggie; Tu, Hai‐Yan; Wei, Xue‐Wu; Yan, Hong‐Hong; Dong, Xiaorong; Cui, Jiuwei; Zhou, Zihan; Xu, Chong-Rui; Zheng, Ming-Ying; Li, Yang-Si; Wang, Zhen; Bai, Xiaoyan; Li, Anna; Sun, Yue‐Li; Huang, Jie; Lin, Jiaxin; Ke, E-E; Xu, Bo; Chang, Lu; Du, Yingying; Chen, Yuan; Ma, Rui; Wang, Buhai; Cang, Shundong; Wang, Bin-Chao; Chen, Hua-Jun; Yang, Jin‐Ji; Li, Yangqiu; Zhou, Qing; Wu, Yi‐Long

doi:10.1038/s41591-023-02461-x

Cited by 23 publications

(6 citation statements)

References 26 publications

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“…Nonetheless, while our overall findings in the subgroup of patients without BRCA/HRR mutations do not advocate for the routine application of PARP inhibitors, sensitivity analysis reminds us that further exploration necessitates more profound and comprehensive pre-clinical and clinical evidence. Furthermore, the concept of "patient-centered clinical trials" has gained significant traction in recent times [42]. Despite the general responsiveness of BRCA/HRR-positive patients to PARP inhibitors, a subset of these patients fails to derive a survival benefit.…”

Section: Discussionmentioning

confidence: 99%

Poly (ADP-ribose) Polymerase Inhibitors in Patients with Metastatic Castration-Resistant Prostate Cancer: A Meta-Analysis of Randomized Controlled Trials

Chao,

Wang,

et al. 2023

Medicina

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Context: Several recent randomized controlled trials (RCTs) have reported on the survival benefits of poly (ADP-ribose) polymerase inhibitors (PARPi) compared to standard-of-care (SOC) treatment (enzalutamide, abiraterone, or docetaxel) in patients with metastatic castration-resistant prostate cancer (mCRPC). However, there is a limited integrated analysis of high-quality evidence comparing the efficacy and safety of PARPi and SOC treatments in this context. Objective: This study aims to comprehensively analyze the survival benefits and adverse events associated with PARPi and SOC treatments through a head-to-head meta-analysis in mCRPC. Evidence acquisition: A systematic review search was conducted in PubMed, Embase, Clinical trials, and the Central Cochrane Registry in July 2023. RCTs were assessed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The systematic review was prospectively registered on PROSPERO (CRD42023441034). Evidence synthesis: A total of 8 studies, encompassing 2341 cases in the PARPi treatment arm and 1810 cases in the controlled arm, were included in the qualitative synthesis. The hazard ratio (HR) for radiographic progression-free survival (rPFS) and overall survival (OS) were 0.74 (95% CI, 0.61–0.90) and 0.89 (95% CI, 0.80–0.99), respectively, in the intention-to-treatment patients. For subgroup analysis, HRs for rPFS and OS in the BRCA-mutated subgroup were 0.39 (95% CI, 0.28–0.55) and 0.62 (95% CI, 0.38–0.99), while in the HRR-mutated subgroup, HR for rPFS was 0.57 (95% CI, 0.48–0.69) and for OS was 0.77 (95% CI, 0.64–0.93). The odds ratio (OR) for all grades of adverse events (AEs) and AEs with severity of at least grade 3 were 3.86 (95% CI, 2.53–5.90) and 2.30 (95% CI, 1.63–3.26), respectively. Conclusions: PARP inhibitors demonstrate greater effectiveness than SOC treatments in HRR/BRCA-positive patients with mCRPC. Further research is required to explore ways to reduce adverse event rates and investigate the efficacy of HRR/BRCA-negative patients.

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Section: Discussionmentioning

confidence: 99%

Poly (ADP-ribose) Polymerase Inhibitors in Patients with Metastatic Castration-Resistant Prostate Cancer: A Meta-Analysis of Randomized Controlled Trials

Chao,

Wang,

et al. 2023

Medicina

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“…This requires collaborative efforts from various stakeholders, forming international alliances to further accelerate the advancement and implementation of precision oncology treatments [68]. CTONG1702/1705 is an open-label, multicenter, phase II adaptive umbrella trial and realworld observational study [69,70]. Patients who meet the strict inclusion criteria of CTONG1702 based on large next-generation sequencing (NGS) panel and PD-L1 expression results are enrolled in parallel sub-studies with treatment regimens matched to their profiles.…”

Section: Level Of Evidence: Moderate Strength Of Recommendation: Mode...mentioning

confidence: 99%

Uncommon/rare oncogenic drivers in non‐small cell lung cancer: Consensus and contention

Wu,

Lu,

Cheng

et al. 2023

Medicine Advances

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The importance of uncommon/rare oncogenic drivers in non‐small cell lung cancer (NSCLC) was underscored during the 20th China Lung Cancer Summit. These drivers, while present in a significant proportion of NSCLC patients, remain a challenge for diagnosis and therapeutic targeting. In the never‐smokers/low smokers category with mutations such as EGFR and HER2, the efficacy of immune checkpoint inhibitors (ICIs) remains suboptimal, attributed to lower PD‐L1 expression and tumor mutation burden (TMB). However, heavy smokers, often with mutations like KRAS, may derive benefits from ICIs, as supported by trials like CheckMate‐057. With the complex landscape of these drivers and their clinical implications, the summit culminated in six pivotal consensus points, aiming to guide future research and clinical decisions. Despite the advancements, the detection, interpretation, and therapeutic strategies involving these drivers necessitate further exploration and standardization.

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“…In clinical research, PYR has demonstrated effective improvements in disease‐free and overall survival in patients with HER2‐positive breast cancer. [ 10 ] Nonetheless, the free form of this small‐molecule chemotherapeutic agent has limitations such as poor bioavailability and short action period, and is associated with systemic and organ toxicity. As an alternative approach, nanoparticle‐based drug delivery has gained increasing attention in breast cancer treatment.…”

Section: Introductionmentioning

confidence: 99%

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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First-line pyrotinib in advanced HER2-mutant non-small-cell lung cancer: a patient-centric phase 2 trial

Cited by 23 publications

References 26 publications

Poly (ADP-ribose) Polymerase Inhibitors in Patients with Metastatic Castration-Resistant Prostate Cancer: A Meta-Analysis of Randomized Controlled Trials

Poly (ADP-ribose) Polymerase Inhibitors in Patients with Metastatic Castration-Resistant Prostate Cancer: A Meta-Analysis of Randomized Controlled Trials

Uncommon/rare oncogenic drivers in non‐small cell lung cancer: Consensus and contention

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

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