LBA15 Primary results from IMpassion131, a double-blind placebo-controlled randomised phase III trial of first-line paclitaxel (PAC) ± atezolizumab (atezo) for unresectable locally advanced/metastatic triple-negative breast cancer (mTNBC)

Miles, D. W.; Gligorov, Joseph; André, Fabrice; Cameron, David; Schneeweiß, Andreas; Barrios, CH; Xu, Binghe; Wardley, Andrew M; Kaen, Diego; Andrade, Livia; Семиглазов, Владимир; Reinisch, Mattea; Patre, Monika; Morales, Leilani; Russell, Kenneth J.; Donica, Margarita; O’Shaughnessy, Joyce

doi:10.1016/j.annonc.2020.08.2243

Cited by 165 publications

(202 citation statements)

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“…Unexpectedly, PD-L1+ status (≥1% PD-L1 staining on immune cells with SP142 assay) did not influence atezolizumab benefit, with even a trend towards a detrimental effect in the preliminary OS analysis. Although hypothetical reasons for inconsistent results may rely on treatment-related factors such as steroid premedication or different backbone chemotherapies, these results may also suggest PD-L1 expression as a suboptimal predictive biomarker in this setting [ 76 , 77 ]. Thus, there is an impelling need to further deepen the biological role as well as the clinical relevance of PD-L1 expression in patients receiving immunotherapy in the advanced setting and to explore other predictors of immunotherapy efficacy [ 78 ].…”

Section: Adaptive Immunitymentioning

confidence: 99%

Immune Infiltrates in Breast Cancer: Recent Updates and Clinical Implications

Dieci

Miglietta

Guarneri

2021

Cells

154

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In recent decades, the increasing interest in the field of immunotherapy has fostered an intense investigation of the breast cancer (BC) immune microenvironment. In this context, tumor-infiltrating lymphocytes (TILs) have emerged as a clinically relevant and highly reproducible biomarker capable of affecting BC prognosis and response to treatment. Indeed, the evaluation of TILs on primary tumors proved to be strongly prognostic in triple-negative (TN) BC patients treated with either adjuvant or neoadjuvant chemotherapy, as well as in early TNBC patients not receiving any systemic treatment, thus gaining level-1b evidence in this setting. In addition, a strong relationship between TILs and pathologic complete response after neoadjuvant chemotherapy has been reported in all BC subtypes and the prognostic role of higher TILs in early HER2-positive breast cancer patients has also been demonstrated. The interest in BC immune infiltrates has been further fueled by the introduction of the first immune checkpoint inhibitors in the treatment armamentarium of advanced TNBC in patients with PD-L1-positive status by FDA-approved assays. However, despite these advances, a biomarker capable of reliably and exhaustively predicting immunotherapy benefit in BC is still lacking, highlighting the imperative need to further deepen this issue. Finally, more comprehensive evaluation of immune infiltrates integrating both the quantity and quality of tumor-infiltrating immune cells and incorporation of TILs in composite scores encompassing other clinically or biologically relevant biomarkers, as well as the adoption of software-based and/or machine learning platforms for a more comprehensive characterization of BC immune infiltrates, are emerging as promising strategies potentially capable of optimizing patient selection and stratification in the research field. In the present review, we summarize available evidence and recent updates on immune infiltrates in BC, focusing on current clinical applications, potential clinical implications and major unresolved issues.

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Section: Adaptive Immunitymentioning

confidence: 99%

Immune Infiltrates in Breast Cancer: Recent Updates and Clinical Implications

Dieci

Miglietta

Guarneri

2021

Cells

154

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“…Again, progression-free and overall survival were co-primary endpoints, and a reverse sequence hierarchical approach was planned, to look at the PD-L1-positive subgroup first and then at the ITT population. However, no benefit from the addition of atezolizumab to PTX was found either in the PD-L1-positive or in the ITT population [ 131 ].…”

Section: Moving From Working Hypothesis To Clinical Trialsmentioning

confidence: 99%

Advanced Nanotechnology for Enhancing Immune Checkpoint Blockade Therapy

et al. 2021

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Immune checkpoint receptor signaling pathways constitute a prominent class of “immune synapse,” a cell-to-cell connection that represses T-lymphocyte effector functions. As a possible evolutionary countermeasure against autoimmunity, this strategy is aimed at lowering potential injury to uninfected cells in infected tissues and at minimizing systemic inflammation. Nevertheless, tumors can make use of these strategies to escape immune recognition, and consequently, such mechanisms represent chances for immunotherapy intervention. Recent years have witnessed the advance of pharmaceutical nanotechnology, or nanomedicine, as a possible strategy to ameliorate immunotherapy technical weaknesses thanks to its intrinsic biophysical properties and multifunctional modifying capability. To improve the long-lasting response rate of checkpoint blockade therapy, nanotechnology has been employed at first for the delivery of single checkpoint inhibitors. Further, while therapy via single immune checkpoint blockade determines resistance and a restricted period of response, strong interest has been raised to efficiently deliver immunomodulators targeting different inhibitory pathways or both inhibitory and costimulatory pathways. In this review, the partially explored promise in implementation of nanotechnology to improve the success of immune checkpoint therapy and solve the limitations of single immune checkpoint inhibitors is debated. We first present the fundamental elements of the immune checkpoint pathways and then outline recent promising results of immune checkpoint blockade therapy in combination with nanotechnology delivery systems.

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“…OS data of KEYNOTE-355 have not yet been presented yet, and these must be awaited before approval of pembrolizumab can be expected. In the light of recent negative results obtained with the combination of paclitaxel and atezolizumab (IMpassion131) [ 3 ], the differential effects of pembrolizumab when added to paclitaxel or nab-paclitaxel needs to be analysed in more detail and these data are eagerly awaited.…”

Section: Keynote-355mentioning

confidence: 99%

ASCO 2020: highlights in breast cancer

Bartsch

2021

memo

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SummaryThe 2020 Annual Meeting of the American Society of Clinical Oncology (ASCO) was held in a virtual format due to the ongoing SARS-CoV‑2 pandemic. Despite these unique circumstances, results of several interesting studies in the field of breast cancer (BC) were reported. While overall survival data are still missing, KEYNOTE-355 suggests significant activity of pembrolizumab when added to first-line chemotherapy in metastatic triple-negative breast cancer. TBCRC 048 evaluated the role of olaparib in homologous recombination deficient tumours due to genomic alterations other than germline BRCA1/2 mutations; clinically relevant activity was reported in patients with germline PALB2 and somatic BRCA1/2 mutations. In HER2-positive early stage disease, different strategies of chemotherapy de-escalation are under investigation, but the optimal approach is still not well defined. Updated results from the HER2CLIMB trial show that the third-generation HER2 tyrosine-kinase inhibitor tucatinib in combination with trastuzumab and capecitabine is the new standard-of-care for pretreated patients with HER2-positive metastatic BC with active brain metastases. Results from BYLieve supports the notion that the combination of endocrine therapy with the PIK3Ca inhibitor alpelisib is a reasonable treatment approach in hormone-receptor positive/HER2-negative BC after prior CDK4/6-inhibitor therapy. Finally, the ECOG-ACRIN 2108 trial failed to show a benefit for early surgery of the primary tumour in patients with metastatic BC.

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LBA15 Primary results from IMpassion131, a double-blind placebo-controlled randomised phase III trial of first-line paclitaxel (PAC) ± atezolizumab (atezo) for unresectable locally advanced/metastatic triple-negative breast cancer (mTNBC)

Cited by 165 publications

References 0 publications

Immune Infiltrates in Breast Cancer: Recent Updates and Clinical Implications

Immune Infiltrates in Breast Cancer: Recent Updates and Clinical Implications

Advanced Nanotechnology for Enhancing Immune Checkpoint Blockade Therapy

ASCO 2020: highlights in breast cancer

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