Pembrolizumab plus Chemotherapy in Advanced Triple-Negative Breast Cancer

Cortés, Javier; Rugo, Hope S.; Cescon, David W.; Im, Sungbin; Yusof, Mastura Md; Gallardo, Carlos; Lipatov, Oleg; Barrios, Carlos H.; Peréz-García, José Manuel; Iwata, Hiroji; Masuda, Norikazu; Otero, Marco Torregroza; Erhan, Gokmen; Sherene, Loi; Guo, Zifang; Zhou, Xuan; Karantza, Vassiliki; Pan, Wilbur; Schmid, Peter

doi:10.1056/nejmoa2202809

Cited by 324 publications

(157 citation statements)

References 22 publications

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“…KEYNOTE-355 trail has investigated the efficacy and safety of immunotherapy (pembrolizumab) added to chemotherapy in 847 advanced TNBC. In patients whose tumors expressed programmed death ligand (PD-L1), pembrolizumab could significantly longer survival than chemotherapy alone 40 . Besides, our previous study, have also shown that novel targeted therapeutic modalities may be an inspiring outlook in triple negative breast cancer 41 .…”

Section: Discussionmentioning

confidence: 99%

Development and validation of nomograms for predicting survival in patients with de novo metastatic triple-negative breast cancer

Chen

Liu

et al. 2022

Sci Rep

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Metastatic triple-negative breast cancer (mTNBC) is a heterogeneous disease with a poor prognosis. Individualized survival prediction tool is useful for this population. We constructed the predicted nomograms for breast cancer-specific survival (BCSS) and overall survival (OS) using the data identified from the Surveillance, Epidemiology, and End Results database. The Concordance index (C-index), the area under the time-dependent receiver operating characteristic curve (AUC) and the calibration curves were used for the discrimination and calibration of the nomograms in the training and validation cohorts, respectively. 1962 mTNBC patients with a median follow-up was 13 months (interquartile range, 6–22 months), 1639 (83.54%) cases died of any cause, and 1469 (74.87%) died of breast cancer. Nine and ten independent prognostic factors for BCSS and OS were identified and integrated to construct the nomograms, respectively. The C-indexes of the nomogram for BCSS and OS were 0.694 (95% CI 0.676–0.712) and 0.699 (95% CI 0.679–0.715) in the training cohort, and 0.699 (95% CI 0.686–0.712) and 0.697 (95% CI 0.679–0.715) in the validation cohort, respectively. The AUC values of the nomograms to predict 1-, 2-, and 3-year BCSS and OS indicated good specificity and sensitivity in internal and external validation. The calibration curves showed a favorable consistency between the actual and the predicted survival in the training and validation cohorts. These nomograms based on clinicopathological factors and treatment could reliably predict the survival of mTNBC patient. This may be a useful tool for individualized healthcare decision-making.

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Section: Discussionmentioning

confidence: 99%

Development and validation of nomograms for predicting survival in patients with de novo metastatic triple-negative breast cancer

Chen

Liu

et al. 2022

Sci Rep

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“…Despite persistent research efforts worldwide, the treatment outcome of gliomas, especially glioblastomas, remains unfavorable. Cancer immunotherapy, targeting enhancing natural defenses to attack malignant cells, has been confirmed to improve outcomes in multiple cancers ( Eggermont et al, 2018 ; Gandhi et al, 2018 ; Choueiri et al, 2021 ; Cortes et al, 2022 ). Nevertheless, almost all immunotherapy attempts on glioblastoma failed to improve overall survival ( Weller et al, 2017 ; Wakabayashi et al, 2018 ; Reardon et al, 2020 ; Lim et al, 2022 ; Omuro et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of cuproptosis-related genes signature and its impact on the reshaped immune microenvironment of glioma

Chen

Zhang²,

Yuan³

et al. 2022

Front. Pharmacol.

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Glioma is the most prevalent malignancy in the central nervous system. The impact of ion-induced cell death on malignant tumors’ development and immune microenvironment has attracted broad attention in recent years. Cuproptosis is a novel copper-dependent mechanism that could potentially regulate tumor cell death by targeting mitochondria respiration. However, the role of cuproptosis in gliomas remains unclear. In the present study, we investigated the relationships between the expression of cuproptosis-related genes (CRGs) and tumor characteristics, including prognosis and microenvironment of glioma, by analyzing multiple public databases and our cohort. Consensus clustering based on the expression of twelve CRGs stratified the glioma patients into three subgroups with significantly different prognosis and immune microenvironment landscapes. Reduced immune infiltration was associated with the less aggressive CRG cluster. A prognostic CRGs risk signature (CRGRS), based on eight critical CRGs, classified the patients into low- and high-risk groups in the training set and was endorsed by validation sets from multiple cohorts. The high-risk group manifested a shorter overall survival, and further survival analysis demonstrated that the CRGRS was an independent prognostic factor. The nomogram combining CRGRS and other clinicopathological factors exhibited good accuracy in predicting the prognosis of glioma patients. Moreover, analyses of tumor immune microenvironment indicated that higher CRGRS was correlated with increased immune cell infiltration but diminished immune function. Gliomas in the high-risk group exhibited higher expression of multiple immune checkpoints, including PD-1 and PD-L1, and a better predicted therapy response to immune checkpoint inhibitors. In conclusion, our study elucidated the connections between CRGs expression and the aggressiveness of gliomas, and the application of CRGRS derived a new robust model for prognosis evaluation of glioma patients. The correlations between the profiles of CRGs expression and immune tumor microenvironment illuminated prospects and potential indications of immunotherapy for glioma.

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“…It is important to mention that regardless of these results, the atezolizumab/nab-paclitaxel combination approval for metastatic TNBC has been withdrawn by the FDA. More importantly, according to the KEYNOTE-355 clinical phase III, the addition of pembrolizumab to chemotherapy led to significantly longer PFS than chemotherapy alone, in patients with PD-L1 + (CPS > 10) mBC TNBC (HR = 0.73; 95% CI, 0.55 to 0.95; p = 0.0185) [ 93 , 94 ]. Further clinical studies with a larger patient cohort are needed to address its effectiveness in PD-L1 + TNBC patients [ 94 ] ( Figure 5 ).…”

Section: Current Treatment Options Of Mbcmentioning

confidence: 99%

“…More importantly, according to the KEYNOTE-355 clinical phase III, the addition of pembrolizumab to chemotherapy led to significantly longer PFS than chemotherapy alone, in patients with PD-L1 + (CPS > 10) mBC TNBC (HR = 0.73; 95% CI, 0.55 to 0.95; p = 0.0185) [ 93 , 94 ]. Further clinical studies with a larger patient cohort are needed to address its effectiveness in PD-L1 + TNBC patients [ 94 ] ( Figure 5 ). Given that TNBC has a higher frequency metastasizing in the brain, a summary of proposed therapeutic choices and indications for brain metastasis mBC are outlined in Table 2 .…”

Section: Current Treatment Options Of Mbcmentioning

confidence: 99%

The Present and Future of Clinical Management in Metastatic Breast Cancer

Lin

Laliotis

2022

JCM

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Regardless of the advances in our ability to detect early and treat breast cancer, it is still one of the common types of malignancy worldwide, with the majority of patients decease upon metastatic disease. Nevertheless, due to these advances, we have extensively characterized the drivers and molecular profiling of breast cancer and further dividing it into subtypes. These subgroups are based on immunohistological markers (Estrogen Receptor-ER; Progesterone Receptor-PR and Human Epidermal Growth Factor Receptor 2-HER-2) and transcriptomic signatures with distinct therapeutic approaches and regiments. These therapeutic approaches include targeted therapy (HER-2+), endocrine therapy (HR+) or chemotherapy (TNBC) with optional combination radiotherapy, depending on clinical stage. Technological and scientific advances in the identification of molecular pathways that contribute to therapy-resistance and establishment of metastatic disease, have provided the rationale for revolutionary targeted approaches against Cyclin-Dependent Kinases 4/6 (CDK4/6), PI3 Kinase (PI3K), Poly ADP Ribose Polymerase (PARP) and Programmed Death-Ligand 1 (PD-L1), among others. In this review, we focus on the comprehensive overview of epidemiology and current standard of care treatment of metastatic breast cancer, along with ongoing clinical trials. Towards this goal, we utilized available literature from PubMed and ongoing clinical trial information from clinicaltrials.gov to reflect the up to date and future treatment options for metastatic breast cancer.

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Pembrolizumab plus Chemotherapy in Advanced Triple-Negative Breast Cancer

Cited by 324 publications

References 22 publications

Development and validation of nomograms for predicting survival in patients with de novo metastatic triple-negative breast cancer

Development and validation of nomograms for predicting survival in patients with de novo metastatic triple-negative breast cancer

Prognostic value of cuproptosis-related genes signature and its impact on the reshaped immune microenvironment of glioma

The Present and Future of Clinical Management in Metastatic Breast Cancer

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