4.6 Review

Treatment landscape of triple-negative breast cancer - expanded options, evolving needs

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Summary: The study evaluated the prevalence of PD-L1 in metastatic triple-negative breast cancer patients, showing variations in different anatomical locations. The findings also suggest a decent agreement in PD-L1 status in paired samples collected synchronously or asynchronously from the same subject.

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Clinical and Biomarker Results from Phase I/II Study of PI3K Inhibitor Alpelisib plus Nab-paclitaxel in HER2-Negative Metastatic Breast Cancer

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Leisha A. Emens et al.

Summary: Understanding the impact of tumor immune microenvironment and BRCA1/2-related DNA repair deficiencies on the clinical activity of immune checkpoint inhibitors in metastatic triple-negative breast cancer may help optimize patient and treatment selection. The study found that PD-L1 expression and CD8-positive cells had an influence on the efficacy of immunotherapy.

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Joshua Z. Drago et al.

Summary: Nine ADCs are currently approved for cancer treatment, with many more in development. Advances in synthetic biochemistry have led to a new generation of ADCs promising improved tissue specificity and cytotoxicity. Despite impressive activity against treatment-refractory cancers, challenges such as systemic toxicity and acquired resistance remain. This review discusses the design, mechanism of action, and limitations of ADCs, proposing strategies to maximize their therapeutic benefit for cancer patients.

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Deborah Blythe Doroshow et al.

Summary: PD-L1 expression is currently the best predictor of responsiveness to immune-checkpoint inhibitors, despite challenges in clinical use such as variability in different assays and cut-off points, as well as the lack of prospective comparisons with clinical outcomes. Nevertheless, several immunohistochemical assays have been approved for clinical use, with implications for pathology services and potential impacts on clinical outcomes. Comparison of FDA-approved PD-L1 assays, understanding of the varying implications of PD-L1 expression across different tumour types, and exploration of novel approaches to optimize its clinical utility are important topics for further research and practice.

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Yujing Li et al.

Summary: The heterozygous loss of chromosome 17p, a common genomic event in breast cancer, leads to global gene expression changes, reduced T cell tumor infiltration, and deletion of tumor suppressor genes like TP53. This loss also makes breast cancer cells sensitive to POLR2A inhibition, enabling targeted precision immunotherapy.

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Summary: Analysis of over 10,000 patient tumors from The Cancer Genome Atlas showed that TMB-H tumors had significantly higher response rates to immune checkpoint blockade in certain cancer types, while showing no significant benefit in others. These results do not support the use of TMB-H as a biomarker for ICB treatment across all solid cancer types, indicating the need for further tumor type-specific studies.

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Summary: The biomarker analysis from the ASCENT trial demonstrates that sacituzumab govitecan (SG) provides improved survival outcomes and objective response rates in previously treated mTNBC patients with high/medium Trop-2 expression compared to standard-of-care chemotherapy (TPC), regardless of germline BRCA1/2 mutation status. The efficacy outcomes were consistently higher with SG compared to TPC in patients with both high/medium Trop-2 expression and those without germline BRCA1/2 mutations.

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First-line atezolizumab plus nab-paclitaxel for unresectable, locally advanced, or metastatic triple-negative breast cancer: IMpassion130 final overall survival analysis

L. A. Emens et al.

Summary: The study showed that although A + nP for first-line treatment of triple-negative breast cancer did not significantly improve overall survival in the overall population, clinically meaningful benefits were observed in patients with PD-L1 expression on tumor infiltrating immune cells. The combination therapy remained safe and tolerable with longer follow-up.

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Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer

D. Miles et al.

Summary: Combining atezolizumab with paclitaxel did not improve PFS or OS in PD-L1-positive aTNBC patients, although it showed some advantage in unconfirmed best overall response rate and duration of response.

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PD-L1 Immunohistochemistry Assay Comparison in Atezolizumab Plus nab-Paclitaxel-Treated Advanced Triple-Negative Breast Cancer

Hope S. Rugo et al.

Summary: This study evaluated different PD-L1 assays for triple-negative breast cancer patients and found that SP263 and 22C3 assays identified more PD-L1+ patients compared to SP142. A+nP treatment showed improved efficacy in patients with SP263+ and 22C3+ tumors compared to placebo+nP, with better outcomes in double-positive cases than single-positive cases. The concordance between different assays for PD-L1 detection was not perfect, and SP142 showed consistent efficacy in the IC >= 1% subgroup within 22C3 and SP263 PD-L1+ populations.

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