Performance of PD-L1 immunohistochemistry (IHC) assays in unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC): Post-hoc analysis of IMpassion130

Rugo, HS; Loi, Sherene; Adams, Sylvia; Schmid, Peter; Schneeweiß, Andreas; Barrios, CH; Iwata, Hiroji; Diéras, V.; Winer, EP; Kockx, Mark; Peeters, Dieter; Chui, Stephen Y.; Lin, J.; Duc, Anh Nguyen; Viale, Giulia; Molinero, Luciana; Emens, Leisha A.

doi:10.1093/annonc/mdz394.009

Cited by 101 publications

(138 citation statements)

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“…64,65 However, mismatch repair deficiency occurs rarely in breast cancer and more commonly in early-stage disease, 64 and most patients with mTNBC are PD-L1negative by the currently approved SP-142 assay. 66 Furthermore, the utility of PD-L1 expression as a reliable biomarker is limited by several issues: its varying expression over time and metastatic sites; the discrepancy among different PD-L1 assays, particularly when staining immune cells 67 ; the observations that some PD-L1-negative patients respond to ICIs 68 ; and recent trials in the early disease setting that show little to no correlation of PD-L1 expression with benefit specific to ICIs, including the KEYNOTE-522 and NeoTRIPaPDL1 trials. 36,69 Emerging potential biomarkers of immunotherapy response in TNBC include high tumor mutational burden (TMB), TILs, and transcriptional signatures of immune infiltration.…”

Section: Biomarkers Of Immunotherapy Responsementioning

confidence: 99%

Role of Immunotherapy in Triple-Negative Breast Cancer

Keenan

Tolaney

2020

Journal of the National Comprehensive Cancer Network

363

298

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Immune checkpoint inhibitors (ICIs) have led to durable clinical remissions in many metastatic cancers. However, the single-agent efficacy of ICIs in breast cancer is low, including in triple-negative breast cancer (TNBC), which has several key characteristics that enhance ICI responses. Strategies to improve anticancer immune responses in TNBC are urgently needed to extend survival for patients with metastatic disease. This review presents ICI monotherapy response rates and discusses combination strategies with chemotherapy, targeted therapies, and novel immunotherapies. It concludes with a summary of immunotherapy biomarkers in TNBC and a call to action for future directions of research critical to advancing the efficacy of immunotherapy for patients with TNBC.Although response rates to ICIs are higher in TNBC than in hormone receptor-positive and HER2-positive breast cancers, the single-agent efficacy is still low, with monotherapy response rates ranging from approximately 5% in

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Section: Biomarkers Of Immunotherapy Responsementioning

confidence: 99%

Role of Immunotherapy in Triple-Negative Breast Cancer

Keenan

Tolaney

2020

Journal of the National Comprehensive Cancer Network

363

298

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“…Tumor specimens of the IMpassion130 cohort have been further analyzed by means of two other clones used in diagnostic practice, the SP263 and the 22C3 with corresponding scoring systems (Table 1). The 22C3 and the SP263 identify a larger number of positive cases (81 and 75%, respectively) compared to SP142 (46%), and a significant correlation with response to atezolizumab was observed also for all of the clones [122]. However, it is important to consider that the subpopulation of cases positive for SP263 and/or the 22C3 but negative for SP142 does not show PFS advantage in the atezolizumab arm, thus demonstrating that the clinical benefit observed for the other two clones is driven by the positive population that is identified by the SP142 clone [122].…”

Section: Immunotherapy In Breast Cancermentioning

confidence: 86%

“…Still we do not have data on direct comparison of paired primary tumor and metastatic sites from the same patient. From a post-hoc analysis performed on the study we know that immunogenicity may vary according to the metastatic site, with liver metastases displaying the lowest level of IC infiltration overall [122].…”

Section: Immunotherapy In Breast Cancermentioning

confidence: 99%

“…However, it is important to consider that the subpopulation of cases positive for SP263 and/or the 22C3 but negative for SP142 does not show PFS advantage in the atezolizumab arm, thus demonstrating that the clinical benefit observed for the other two clones is driven by the positive population that is identified by the SP142 clone [122]. In addition, the SP142 assay identified patients with the smallest hazard ratio point estimates and longest median PFS and OS from atezolizumab plus nab-paclitaxel [122].…”

Section: Immunotherapy In Breast Cancermentioning

confidence: 99%

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The Multifaceted Nature of Tumor Microenvironment in Breast Carcinomas

et al. 2020

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Heterogeneity in breast carcinomas can be appreciated at various levels, from morphology to molecular alterations, and there are well-known genotypic-phenotypic correlations. Clinical decision-making is strictly focused on the evaluation of tumor cells and is based on the assessment of hormone receptors and of the HER2 status, by means of a combination of immunohistochemical and in situ hybridization techniques. The tumor microenvironment (TME) also shows a multifaceted nature stemming from the different actors populating the intratumoral and the peritumoral stroma of breast carcinomas. Of note, we have now evidence that tumor-infiltrating lymphocytes (TILs) are clinically meaningful as their quantification in the intratumoral stroma strongly correlates with good prognosis, in particular in triple-negative and HER2-positive breast cancer patients. Nevertheless, TILs are just one of the many actors orchestrating the com-plexity of the TME, which is populated by immune and nonimmune cells (cancer-associated fibroblasts, cancer-associated adipocytes), as well as non-cellular components such as chemical inflammation mediators. In this review article we will overview the main features of the distinct cell compartments by discussing (i) the potential impact the TME may have on the prognostic stratification of breast cancers and (ii) the possible predictive value of some markers in the context of immunotherapy in light of the recent results of phase III studies in advanced and early triple-negative breast cancer patients.

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“…Although the results of the IMpassion130 are certainly practice changing, yet it is essential to evoke the useless role of atezolizumab in patients with PD‐L1‐negative tumors (around 60% of all mTNBC). This notion underscores the crucial role of adequate PD‐L1 testing in these tumors, exclusively by the SP 142 assay, rather than any other commercially available assays, which were recently found to have an inferior capability to predict atezolizumab benefit in mTNBC …”

Section: Exploring Genetic Events To Tailor Therapy Of Mtnbcmentioning

confidence: 96%

Personalized treatment in metastatic triple‐negative breast cancer: The outlook in 2020

et al. 2019

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Compared with other breast cancer subtypes, patients with triple‐negative breast cancer (TNBC), and irrespective to their disease stage, were always recognized to have the worst overall survival data. Although this does not seem different at the present time, yet the last few years have witnessed many breakthrough genomic and molecular findings, that could dramatically improve our understanding of the biological complexity of TNBC. Based on genomic analyses, it was consistently evident that TNBC comprises a heterogeneous group of cancers, which have numerous diverse molecular aberrations. This—in return—has provided a platform for a new generation of clinical trials using many innovative therapies, directed against such novel targets. At the present time, two PARP inhibitors and one anti‐PD‐L1 monoclonal antibody (in combination with chemotherapy) have been approved in certain subpopulations of metastatic TNBC (mTNBC) patients, which have finally brought this disease into the era of personalized medicine. In the current review, we will explore the genomic landscape of TNBC, through which many actionable targets were graduated. We will also discuss the results of the key—practice changing—clinical studies, and some upcoming personalized treatment options for patients with mTNBC, that may be clinically adopted in the near future.

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Performance of PD-L1 immunohistochemistry (IHC) assays in unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC): Post-hoc analysis of IMpassion130

Cited by 101 publications

References 0 publications

Role of Immunotherapy in Triple-Negative Breast Cancer

Role of Immunotherapy in Triple-Negative Breast Cancer

The Multifaceted Nature of Tumor Microenvironment in Breast Carcinomas

Personalized treatment in metastatic triple‐negative breast cancer: The outlook in 2020

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