Abemaciclib plus non-steroidal aromatase inhibitor or fulvestrant in women with HR+/HER2- advanced breast cancer: Final results of the randomized phase III MONARCH plus trial.

BACKGROUND: In the interim analysis of MONARCH plus, adding abemaciclib to endocrine therapy (ET) improved progression-free survival (PFS) and objective response rate (ORR) in predominantly Chinese postmenopausal women with HR+/HER2- advanced breast cancer (ABC). This study presents the final pre-planned PFS analysis. METHODS: In the phase III MONARCH plus study, postmenopausal women in China, India, Brazil, and South Africa with HR+/HER2- ABC without prior systemic therapy in an advanced setting (cohort A) or progression on prior ET (cohort B) were randomized (2:1) to abemaciclib (150 mg twice daily [BID]) or placebo plus: anastrozole (1.0 mg/day) or letrozole (2.5 mg/day) (cohort A) or fulvestrant (500 mg) (cohort B). The primary endpoint was PFS of cohort A. Secondary endpoints included cohort B PFS (key secondary endpoint), ORR, overall survival (OS), safety, and health-related quality of life (HRQoL). RESULTS: In cohort A (abemaciclib: n  = 207; placebo: n  = 99), abemaciclib plus a non-steroidal aromatase inhibitor improved median PFS vs . placebo (28.27 months vs . 14.73 months, hazard ratio [HR]: 0.476; 95% confidence interval [95% CI]: 0.348-0.649). In cohort B (abemaciclib: n  = 104; placebo: n  = 53), abemaciclib plus fulvestrant improved median PFS vs . placebo (11.41 months vs . 5.59 months, HR: 0.480; 95% CI: 0.322-0.715). Abemaciclib numerically improved ORR. Although immature, a trend toward OS benefit with abemaciclib was observed (cohort A: HR: 0.893, 95% CI: 0.553-1.443; cohort B: HR: 0.512, 95% CI: 0.281-0.931). The most frequent grade ≥3 adverse events in the abemaciclib arms were neutropenia, leukopenia, anemia (both cohorts), and lymphocytopenia (cohort B). Abemaciclib did not cause clinically meaningful changes in patient-reported global health, functioning, or most symptoms vs . placebo. CONCLUSIONS: Abemaciclib plus ET led to improvements in PFS and ORR, a manageable safety profile, and sustained HRQoL, providing clinical benefit without a high toxicity burden or reduced quality of life. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02763566).

Abemaciclib combined with endocrine therapy as adjuvant treatment for hormone-receptor-positive, HER2-, high-risk early breast cancer: 5-year Chinese population analysis of the phase III randomized monarchE study.

Background: Abemaciclib was the first cyclin-dependent kinase 4/6 (CDK4/6) inhibitor approved globally in the adjuvant setting for high-risk hormone-receptor positive (HR+)/human epidermal growth factor 2 negative (HER2-) early breast cancer (EBC), based on the phase III monarchE trial. Objective: To report an exploratory Chinese population analysis based on the preplanned overall survival (OS) interim analysis with 5-year efficacy results of monarchE. Design and methods: Patients with HR+/HER2-, high-risk (⩾4 positive lymph nodes, or 1-3 nodes and either tumor size ⩾5 cm, histologic grade 3, or Ki-67 ⩾20%) EBC were randomized (1:1) to abemaciclib (150 mg twice daily for 2 years) plus endocrine therapy (ET), or ET alone. This analysis included Chinese patients enrolled in mainland China, Hong Kong, and Taiwan. The primary endpoint was invasive disease-free survival (IDFS); key secondary endpoints included distant relapse-free survival (DRFS), safety, and patient-reported outcomes (PROs). Results: Overall, 501 Chinese patients were included (abemaciclib + ET, n = 259; ET, n = 242). With a median follow-up of 53 months, the addition of abemaciclib to ET resulted in improvements in IDFS (estimated 5-year IDFS rate: 85.9% vs 79.1%; hazard ratio (HR), 0.65 (95% confidence interval (CI) 0.41-1.03)) and DRFS (estimated 5-year DRFS rate: 88.4% vs 82.3%; HR, 0.65 (95% CI, 0.39-1.07)). The most common grade ⩾3 treatment-emergent adverse events in the abemaciclib + ET versus ET groups were neutropenia (24.7% vs 0.8%) and leukopenia (22.4% vs 0.4%). Generally, no clinically meaningful difference in PROs (endocrine symptoms and fatigue) was observed between groups, except for diarrhea. Conclusion: At this prespecified OS interim analysis, which provides 5-year data, the addition of abemaciclib to ET in Chinese patients with high-risk HR+, HER2- EBC was associated with sustained and clinically meaningful improvements in IDFS and DRFS, with acceptable safety and tolerability profiles and minimal impact on PROs. These results represent the first full report of a CDK4/6 inhibitor in Chinese patients with EBC and support the positive benefit-risk profile of adjuvant abemaciclib + ET in Chinese patients. Trial registration: ClinicalTrials.gov identifier: NCT03155997 (first posted: May 16, 2017).

Corrigendum: Identification of oxidative stress-related diagnostic markers and immune infiltration features for idiopathic pulmonary fibrosis by bibliometrics and bioinformatics.

[This corrects the article DOI: 10.3389/fmed.2024.1356825.].

A prospective study of Acupuncture Combined With Modified Blood and Vessel Expelling Blood Stasis Tang in Treating Poststroke Facial Paralysis With Insomnia.

OBJECTIVE: This study aimed to assess the clinical efficacy of acupuncture combined with modified Blood and Vessel Expelling Blood Stasis Tang in the treatment of poststroke patients experiencing facial paralysis and insomnia. METHODS: A total of 120 patients with poststroke facial paralysis and insomnia were selected from the Department of Acupuncture and Moxibustion at the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine between January 2021 and January 2023. They were randomly assigned to either a control group or a study group, with 60 patients in each group. The control group received conventional treatment, while the study group received acupuncture combined with modified Blood and Vessel Expelling Blood Stasis Tang. The neurological function, facial paralysis, and sleep quality of the patients in both groups were compared. RESULTS: The study group exhibited a significantly higher total effective rate compared with the control group (86.67% versus 66.67%). After treatment, both groups showed a significant reduction in National Institutes of Health Stroke Scale scores, with the study group demonstrating significantly lower scores than the control group. The Functional Disability Index scores for somatic functioning and social life functioning significantly improved in both groups after treatment, with the study group achieving significantly lower scores compared with the control group. The Sleep-Related Symptom Scale and Pittsburgh Sleep Quality Index scores significantly decreased in both groups after treatment, with the study group achieving significantly lower scores than the control group. CONCLUSIONS: Acupuncture combined with modified Blood and Vessel Expelling Blood Stasis Tang effectively promotes recovery of neurological function and significantly improves facial paralysis and insomnia in patients with poststroke facial paralysis and insomnia. However, further research is warranted to validate these findings.

Stellate ganglion, inflammation, and arrhythmias: a new perspective on neuroimmune regulation.

Current research on the stellate ganglion (SG) has shifted from merely understanding its role as a collection of neurons to recognizing its importance in immune regulation. As part of the autonomic nervous system (ANS), the SG plays a crucial role in regulating cardiovascular function, particularly cardiac sympathetic nerve activity. Abnormal SG function can lead to disordered cardiac electrical activity, which in turn affects heart rhythm stability. Studies have shown that excessive activity of the SG is closely related to the occurrence of arrhythmias, especially in the context of inflammation. Abnormal activity of the SG may trigger excessive excitation of the sympathetic nervous system (SNS) through neuroimmune mechanisms, thereby increasing the risk of arrhythmias. Simultaneously, the inflammatory response of the SG further aggravates this process, forming a vicious cycle. However, the causal relationship between SG, inflammation, and arrhythmias has not yet been fully clarified. Therefore, this article deeply explores the key role of the SG in arrhythmias and its complex relationship with inflammation, providing relevant clinical evidence. It indicates that interventions targeting SG function and inflammatory responses have potential in preventing and treating inflammation-related arrhythmias, offering a new perspective for cardiovascular disease treatment strategies.

Identification of oxidative stress-related diagnostic markers and immune infiltration features for idiopathic pulmonary fibrosis by bibliometrics and bioinformatics.

Idiopathic pulmonary fibrosis (IPF) garners considerable attention due to its high fatality rate and profound impact on quality of life. Our study conducts a comprehensive literature review on IPF using bibliometric analysis to explore existing hot research topics, and identifies novel diagnostic and therapeutic targets for IPF using bioinformatics analysis. Publications related to IPF from 2013 to 2023 were searched on the Web of Science Core Collection (WoSCC) database. Data analysis and visualization were conducted using CiteSpace and VOSviewer software primarily. The gene expression profiles GSE24206 and GSE53845 were employed as the training dataset. The GSE110147 dataset was employed as the validation dataset. We identified differentially expressed genes (DEGs) and differentially expressed genes related to oxidative stress (DEOSGs) between IPF and normal samples. Then, we conducted Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The hub genes were screened by protein-protein interaction (PPI) networks and machine learning algorithms. The CIBERSORT was used to analyze the immune infiltration of 22 kinds of immune cells. Finally, we conducted the expression and validation of hub genes. The diagnostic efficacy of hub genes was evaluated by employing Receiver Operating Characteristic (ROC) curves and the associations between hub genes and immune cells were analyzed. A total of 6,500 articles were identified, and the annual number of articles exhibited an upward trend. The United States emerged as the leading contributor in terms of publication count, institutional affiliations, highly cited articles, and prolific authorship. According to co-occurrence analysis, oxidative stress and inflammation are hot topics in IPF research. A total of 1,140 DEGs were identified, and 72 genes were classified as DEOSGs. By employing PPI network analysis and machine learning algorithms, PON2 and TLR4 were identified as hub genes. A total of 10 immune cells exhibited significant differences between IPF and normal samples. PON2 and TLR4, as oxidative stress-related genes, not only exhibit high diagnostic efficacy but also show close associations with immune cells. In summary, our study highlights oxidative stress and inflammation are hot topics in IPF research. Oxidative stress and immune cells play a vital role in the pathogenesis of IPF. Our findings suggest the potential of PON2 and TLR4 as novel diagnostic and therapeutic targets for IPF.

Chinese Society of Clinical Oncology (CSCO) Breast Cancer guidelines 2024.

Background: Developing guidelines for the diagnosis and treatment of common cancers in China based on the evidence-based practice, the availability of diagnosis and treatment products, and the up-to-date advances in precision medicine is one of the basic tasks of the Chinese Society of Clinical Oncology Breast Cancer (CSCO BC) Committee. Methods: Protocols with high evidence level and good availability are used as the Level I recommendations; protocols with relatively high evidence level but slightly lower expert consensus or with poor availability are used as the Level II recommendations; and protocols that are clinically applicable but with low evidence level are regarded as the Level III recommendations. Based on the findings of clinical research at home and abroad and the opinions of CSCO BC experts, the CSCO BC guidelines determine the levels of recommendations for clinical application. Results: For human epidermal growth factor receptor 2 (HER2)-positive breast cancer, a combination of trastuzumab and pertuzumab regimen were recommended as Level I recommendation for neoadjuvant and first line metastatic breast cancer. Pyrotinib is also recommended as Level I recommendation in first line and second line therapy according to the latest studies conducted in China. Antibody drug conjugates was also recommended for patients with trastuzumab progression. For triple negative breast cancer, immunotherapy in early and metastatic breast cancer was highlighted and listed as new chapters in this version of guideline. For hormone receptor (HR)-positive breast cancer, cyclin dependent kinase 4/6 (CDK4/6) was recommended in different stages, especially in adjuvant therapy. There was also a new chapter for HER2-low breast cancer stratified by HR status. Conclusions: We firmly believe that evidence-based, availability-concerned, and consensus-based guidelines will be more feasible for clinical practice in China and in other countries with similar situations.

De-escalation of neoadjuvant taxane and carboplatin therapy in HER2-positive breast cancer with dual HER2 blockade: a multicenter real-world experience in China.

BACKGROUND: TCbHP (taxane + carboplatin + trastuzumab + pertuzumab) is the preferred neoadjuvant therapy regimen for human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, no consensus exists regarding whether specific populations may be exempt from carboplatin, allowing for de-escalation to the THP (taxane + trastuzumab + pertuzumab) regimen. Additionally, the optimal number of cycles for neoadjuvant THP remains unclear. We compared the efficacy and safety of neoadjuvant TCbHP and THP regimens, providing clinicians with a nuanced perspective to guide their treatment regimen selection. METHODS: This multicenter real-world study included patients with HER2-positive breast cancer undergoing neoadjuvant TCbHP or THP between March 2019 and February 2023. Efficacy was assessed through the pathological complete response (pCR) rate, while safety was evaluated through monitoring adverse events. RESULTS: Among 220 patients, 103 received 6 cycles of TCbHP (TCbHP×6), 83 received 6 cycles of THP (THP×6), and 34 received 4 cycles of THP (THP×4). The TCbHP×6 cohort exhibited a 66% pCR rate compared with 53% in the THP×6 cohort (P = 0.072). Subgroup analysis revealed that in patients aged ≤ 50 years, those with hormone receptor (HR)-negative status, and those with clinical stage T2, the pCR rate of the TCbHP×6 regimen was significantly higher than the THP×6 regimen (P < 0.05). The TCbHP×6 cohort reported higher frequencies of any-grade adverse events (99% versus 86.7%) and grade 3-4 events (49.5% versus 12%) than the THP×6 cohort. Propensity score matching identified 27 patient pairs between the THP×6 and THP×4 cohorts, indicating a significantly higher pCR rate for the THP×6 regimen than the THP×4 regimen (63% versus 29.6%, P = 0.029). CONCLUSIONS: The TCbHP×6 regimen is favored for individuals aged ≤ 50 years and those aged > 50, ≤60 years with HR-negative status or clinical stage T2-4. For patients in compromised general condition or lacking the specified indications, the THP×6 regimen emerges as a lower-toxicity alternative with satisfactory efficacy. To ensure treatment efficacy, a minimum of 6 cycles of neoadjuvant THP is required.

Omicron neutralization character in patients with breast cancer and liver cancer after the nationwide omicron outbreak.

BACKGROUND: The surge in omicron variants has caused nationwide breakthrough infections in mainland China since the December 2022. In this study, we report the neutralization profiles of serum samples from the patients with breast cancer and the patients with liver cancer who had contracted subvariant breakthrough infections. METHODS: In this real-world study, we enrolled 143 COVID-19-vaccinated (81 and 62 patients with breast and liver cancers) and 105 unvaccinated patients with cancer (58 and 47 patients with breast and liver cancers) after omicron infection. Anti-spike receptor binding domain (RBD) IgGs and 50% pseudovirus neutralization titer (pVNT50) for the preceding (wild type), circulating omicron (BA.4-BA.5, and BF.7), and new subvariants (XBB.1.5) were comprehensively analyzed. RESULTS: Patients with liver cancer receiving booster doses had higher levels of anti-spike RBD IgG against circulating omicron (BA.4-BA.5, and BF.7) and a novel subvariant (XBB.1.5) compared to patients with breast cancer after breakthrough infection. Additionally, all vaccinated patients produced higher neutralizing antibody titers against circulating omicron (BA.4-BA.5, and BF.7) compared to unvaccinated patients. However, the unvaccinated patients produced higher neutralizing antibody against XBB.1.5 than vaccinated patients after Omicron infection, with this trend being more pronounced in breast cancer than in liver cancer patients. Moreover, we found that there was no correlation between anti-spike RBD IgG against wildtype virus and the neutralizing antibody titer, but a positive correlation between anti-spike RBD IgG and the neutralizing antibody against XBB.1.5 was found in unvaccinated patients. CONCLUSION: Our study found that there may be differences in vaccine response and protective effect against COVID-19 infection in patients with liver and breast cancer. Therefore, we recommend that COVID-19 vaccine strategies should be optimized based on vaccine components and immunology profiles of different patients with cancer.

The features of male breast cancer in China: A real-world study.

BACKGROUND: Male breast cancer (MBC) is a rare disease. Although several large-scale studies have investigated MBC patients in other countries, the features of MBC patients in China have not been fully explored. This study aims to explore the features of Chinese MBC patients comprehensively. METHODS: We retrospectively collected data of MBC patients from 36 centers in China. Overall survival (OS) was evaluated by the Kaplan-Meier method, log-rank test, and Cox regression analyses. Multivariate Cox analyses were used to identify independent prognostic factors of the patients. RESULTS: In total, 1119 patients were included. The mean age at diagnosis was 60.9 years, and a significant extension over time was observed (P < 0.001). The majority of the patients (89.1 %) received mastectomy. Sentinel lymph node biopsy was performed in 7.8 % of the patients diagnosed in 2009 or earlier, and this percentage increased significantly to 38.8 % in 2020 or later (P < 0.001). The five-year OS rate for the population was 85.5 % [95 % confidence interval (CI), 82.8 %-88.4 %]. Multivariate Cox analysis identified taxane-based [T-based, hazard ratio (HR) = 0.32, 95 % CI, 0.13 to 0.78, P = 0.012] and anthracycline plus taxane-based (A + T-based, HR = 0.47, 95 % CI, 0.23 to 0.96, P = 0.037) regimens as independent protective factors for OS. However, the anthracycline-based regimen showed no significance in outcome (P = 0.175). CONCLUSION: As the most extensive MBC study in China, we described the characteristics, treatment and prognosis of Chinese MBC population comprehensively. T-based and A + T-based regimens were protective factors for OS in these patients. More research is required for this population.

A Two-color Single-molecule Sequencing Platform and Its Clinical Applications.

DNA sequencers have become increasingly important research and diagnostic tools over the past 20 years. In this study, we developed a single-molecule desktop sequencer, GenoCare 1600 (GenoCare), which utilizes amplification-free library preparation and two-color sequencing-by-synthesis chemistry, making it more user-friendly compared with previous single-molecule sequencing platforms for clinical use. Using the GenoCare platform, we sequenced an Escherichia coli standard sample and achieved a consensus accuracy exceeding 99.99%. We also evaluated the sequencing performance of this platform in microbial mixtures and coronavirus disease 2019 (COVID-19) samples from throat swabs. Our findings indicate that the GenoCare platform allows for microbial quantitation, sensitive identification of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, and accurate detection of virus mutations, as confirmed by Sanger sequencing, demonstrating its remarkable potential in clinical application.

Expert consensus on the clinical application of immunotherapy in breast cancer: 2024.

Background: Significant progress has been made in immunotherapy of breast cancer (BC) with the approval of multiple immune checkpoint inhibitors (ICIs), particularly in early and metastatic triple-negative breast cancer (TNBC) settings. Most guidelines have recommended immune therapy as the important approach in BC, yet several critical aspects still require further clarification, including proper patient selection, treatment duration, optimized chemotherapy partner, predictive biomarkers, and specific considerations for Chinese patients. Methods: (I) Establishment of expert group: the expert group consists of 32 experts from departments such as medical oncology, breast surgery, and pathology; (II) literature search: mainly conducted in English databases (such as PubMed, Embase, and Cochrane Library) and Chinese databases (such as China National Knowledge Infrastructure, China Biology Medicine disc, and Wanfang Database), with a search cutoff date of April 23, 2024; (III) assessment of evidence quality and recommendation strength: evidence quality and recommendation opinions are graded based on the evidence category and recommendation level of the Chinese Society of Clinical Oncology (CSCO) guidelines; (IV) consensus formulation: on the March 2, 2024, through online consensus meeting, the consensus content is thoroughly discussed, and opinions from all experts are solicited. Results: The consensus meeting has resulted in 15 detailed recommendations, providing clearer guidance on the clinical application of immunotherapy in BC management. The core suggestions are as follows: for early-stage II-III TNBC and metastatic TNBC (mTNBC) in the first-line setting, programmed cell death protein 1 (PD-1) inhibitors can be considered. However, for hormone receptor-positive/human epidermal growth factor receptor 2-negative BC (HR+/HER2- BC), HER2+ BC, and mTNBC in later lines of therapy, evidence is lacking to support the use of immunotherapy. Conclusions: This consensus provides a comprehensive overview of BC immunotherapy, including immunotherapy for early-stage BC and late-stage BC, immune related adverse event (irAE) management, biomarkers of immunotherapy, and future directions. The consensus consolidates these deliberations into 15 evidence-based recommendations, serving as a practical guide for clinicians to more scientifically and systematically manage the clinical application of immunotherapy.

P2X7 receptor is essential for ST36-attenuated cardiac fibrosis upon beta-adrenergic insult.

P2X7 receptor (P2X7R) plays an important role in modulating inflammation and fibrosis, but information is limited whether Zusanli (ST36) can inhibit inflammation and fibrosis by regulating P2X7R. Isoprenaline at 5 mg/kg was subcutaneously injected to wild-type and P2X7R knockout mice for 7 days, while treatment groups received electroacupuncture (EA) stimulation at ST36 for 7 sessions. Following 7-session treatment, Masson's trichrome staining was performed to assess the fibrosis. Morphology, electrocardiogram, and echocardiography were carried out to evaluate the cardiac function and structure. Western blotting, hematoxylin and eosin staining, immunohistochemistry, and biochemical analysis of inflammatory cytokine and transmission electron microscopy were carried out to characterize the effect of ST36 on inflammation. P2X7R was overexpressed in ISO-treated mice. EA at ST36, but not at non-points, reduced ISO-induced cardiac fibrosis, increases in HW/BW, R+S wave relative to mice in ISO groups. In addition, EA at ST36 downregulated ISO-upregulated P2X7R and NLRP3 in ventricle. Moreover, EA reduced cytokines of IL-1ß, IL-6, and IL-18 in serum, and inhibited foam cell gathering, inflammatory cell infiltration, and autophagy. However, EA at ST36 failed to attenuate the cardiac fibrosis and hypertrophy in P2X7R knockout mice. In conclusion, EA at ST36 attenuated ISO-induced fibrosis possibly via P2X7R.

A real-world comparison of circulating tumor cells in breast cancer from China: Novel device, CTC counts and its overall survival.

Background: Both CellSearch and CellCollector have been accepted as the proper devices to capture CTC by domestic approval department. However, there is little article about the comparison between these two devices around the world. Herein, we conducted the real-world study to compare with these two devices and to re-verify the efficacy of CTC counts. Methods: Patients who meet the following points should be included in the analysis. 1. Female, aged 18 years or older; 2. Eastern Cooperative Oncology Group (ECOG) score 0-2; 3. With at least one measurable tumor lesion; 4. Clear immunohistochemistry result; 5. Accept at least one CTC test. Patients were excluded in the analysis if they had a history of malignant tumors, incomplete follow-up information. Results: 536 metastatic breast cancer patients who had been detected for CTC at least once by CellSearch or CellCollector were included in the analysis. CellCollector in vivo CTC detection technology has a higher detection rate than the CellSearch system (69.2% vs 57.4%, P = 0.009). However, the proportion of CTC≥5 detected by CellSearch was higher than CellCollector (37.4% vs 16.3%, P < 0.001). There was a statistically significant difference in overall survival of patients with CTC negative and CTC positive (mOS:49.8 months vs 26.9 months). After 4 weeks of treatment, when CTC decreased by more than 50%, there was a significant difference in survival between the two groups (40.1 months vs 25.8 months, HR = 0.588, 95% CI: 0.350-0.933). In addition, for HER2-positive patients, Patients with CTC HER2 positive had longer overall survival than patients with CTC HER2 negative (median OS: 26.7 months vs 17.3 month, HR = 0.528, 95% CI: 0.269-0.887). Conclusions: Real-world data indicate that CTC is an independent prognostic factor, and CellCollector and CellSearch have their own advantages in CTC detection.

Neoadjuvant-adjuvant pertuzumab in HER2-positive early breast cancer: final analysis of the randomized phase III PEONY trial.

The randomized, multicenter, double-blind, placebo-controlled, phase III PEONY trial (NCT02586025) demonstrated significantly improved total pathologic complete response (primary endpoint) with dual HER2 blockade in HER2-positive early/locally advanced breast cancer, as previously reported. Here, we present the final, long-term efficacy (secondary endpoints: event-free survival, disease-free survival, overall survival) and safety analysis (62.9 months' median follow-up). Patients (female; n = 329; randomized 2:1) received neoadjuvant pertuzumab/placebo with trastuzumab and docetaxel, followed by adjuvant 5-fluorouracil, epirubicin, and cyclophosphamide, then pertuzumab/placebo with trastuzumab until disease recurrence or unacceptable toxicity, for up to 1 year. Five-year event-free survival estimates are 84.8% with pertuzumab and 73.7% with placebo (hazard ratio 0.53; 95% confidence interval 0.32-0.89); 5-year disease-free survival rates are 86.0% and 75.0%, respectively (hazard ratio 0.52; 95% confidence interval 0.30-0.88). Safety data are consistent with the known pertuzumab safety profile and generally comparable between arms, except for diarrhea. Limitations include the lack of ado-trastuzumab emtansine as an option for patients with residual disease and the descriptive nature of the secondary, long-term efficacy endpoints. PEONY confirms the positive benefit:risk ratio of neoadjuvant/adjuvant pertuzumab, trastuzumab, and docetaxel treatment in this patient population.

Efficacy, Safety, and Population Pharmacokinetics of MW032 Compared With Denosumab for Solid Tumor-Related Bone Metastases: A Randomized, Double-Blind, Phase 3 Equivalence Trial.

Importance: The bioequivalence of denosumab biosimilar has yet to be studied in a 53-week, multicenter, large-scale, and head-to-head trial. A clinically effective biosimilar may help increase access to denosumab in patients with solid tumor-related bone metastases. Objectives: To establish the biosimilarity of MW032 to denosumab in patients with solid tumor-related bone metastases based on a large-scale head-to-head study. Design, Setting, and Participants: In this 53-week, randomized, double-blind, phase 3 equivalence trial, patients with solid tumors with bone metastasis were recruited from 46 clinical sites in China. Overall, 856 patients were screened and 708 eligible patients were randomly allocated to receive either MW032 or denosumab. Interventions: Patients were randomly assigned (1:1) to receive MW032 or reference denosumab subcutaneously every 4 weeks until week 49. Main Outcomes and Measures: The primary end point was percentage change from baseline to week 13 of natural logarithmic transformed urinary N-telopeptide/creatinine ratio (uNTx/uCr). Results: Among the 701 evaluable patients (350 in the MW032 group and 351 in the denosumab group), the mean (range) age was 56.1 (22.0-86.0) years and 460 patients were women (65.6%). The mean change of uNTx/uCr from baseline to week 13 was -72.0% (95% CI, -73.5% to -70.4%) in the MW032 group and -72.7% (95% CI, -74.2% to -71.2%) in the denosumab group. These percent changes corresponded to mean logarithmic ratios of -1.27 and -1.30, or a difference of 0.02. The 90% CI for the difference (-0.04 to 0.09) was within the equivalence margin (-0.13 to 0.13); the mean changes of uNTx/uCr and bone-specific alkaline phosphatase (s-BALP) at each time point were also similar during 53 weeks. The differences of uNTx/uCr change were 0.015 (95% CI, -0.06 to 0.09), -0.02 (95% CI, -0.09 to 0.06), -0.05 (95% CI, -0.13 to 0.03) and 0.001 (95% CI, -0.10 to 0.10) at weeks 5, 25, 37, and 53, respectively. The differences of s-BALP change were -0.006 (95% CI, 0.06 to 0.05), 0.00 (95% CI, -0.07 to 0.07), -0.085 (95% CI, -0.18 to 0.01), -0.09 (95% CI, -0.20 to 0.02), and -0.13 (95% CI, -0.27 to 0.004) at weeks 5, 13, 25, 37 and 53, respectively. No significant differences were observed in the incidence of skeletal-related events (-1.4%; 95% CI, -5.8% to 3.0%) or time to first on-study skeletal-related events (unadjusted HR, 0.86; P = .53; multiplicity adjusted HR, 0.87; P = .55) in the 2 groups. Conclusions and Relevance: MW032 and denosumab were biosimilar in efficacy, population pharmacokinetics, and safety profile. Availability of denosumab biosimilars may broaden the access to denosumab and reduce the drug burden for patients with advanced tumors. Trial Registration: ClinicalTrials.gov Identifier: NCT04812509.

Toripalimab plus nab-paclitaxel in metastatic or recurrent triple-negative breast cancer: a randomized phase 3 trial.

The combination of immune-checkpoint blockade with chemotherapy for the first-line treatment of advanced triple-negative breast cancer (TNBC) has generated mixed results. TORCHLIGHT is a randomized, double-blinded phase 3 trial evaluating the efficacy and safety of first-line toripalimab and nab-paclitaxel (nab-P) (n = 353; experimental arm) versus placebo and nab-P (n = 178; control arm) for the treatment of women with metastatic or recurrent TNBC. The primary end point was progression-free survival (PFS) assessed by a blinded independent central review in the PD-L1-positive and intention-to-treat populations. The secondary end points included overall survival and safety. Overall, 200 and 100 patients, in the toripalimab and placebo arm respectively had PD-L1-positive TNBC. At the prespecified interim analysis, a statistically significant improvement in PFS assessed by a blinded independent central review was demonstrated in the experimental arm in the PD-L1-positive population (median PFS 8.4 versus 5.6 months; hazard ratio (HR) = 0.65, 95% confidence interval (CI) 0.470-0.906, P = 0.0102). The median overall survival was 32.8 versus 19.5 months (HR = 0.62, 95% CI 0.414-0.914, P = 0.0148). Similar incidences of treatment-emergent adverse events (AEs) (99.2% versus 98.9%), grade ≥3 treatment-emergent AEs (56.4% versus 54.3%) and fatal AEs (0.6% versus 3.4%) occurred in the experimental and control arms. The addition of toripalimab to nab-P provided a significant improvement in PFS for PD-L1-positive patients with metastatic or recurrent TNBC with an acceptable safety profile. ClinicalTrial.gov identifier NCT03777579 .

Antibody drug conjugates in breast cancer in China: Highlights, challenges, and prospects.

Antibody drug conjugates (ADCs) are novel drugs that exert specific cytotoxicity against tumor cells. China approved T-Dxd in May 2023, and their introduction has changed the nation's clinical practice. Although more than 700 ADCs are being investigated worldwide, the challenges that remain in antibody engineering, drug discovery, safety management, resistance, drug selection, and sequencing hinder the further promotion and application of ADCs. Experts in China have discussed the several critical concerns related to clinical practice since 2022. Here, the authors conducted a review of ADCs and then discussed several ADCs explored in China. This study proposes several solutions and strategies to maximize the potential benefit that ADCs can provide to patients with breast cancer.