Pembrolizumab versus investigator-choice chemotherapy for metastatic triple-negative breast cancer (KEYNOTE-119): a randomised, open-label, phase 3 trial

Winer, Eric P.; Lipatov, Oleg; Im, Seock‐Ah; Gonçalves, Anthony; Muñoz‐Couselo, Eva; Lee, Keun Seok; Schmid, Peter; Tamura, Kenji; Testa, Laura; Witzel, Isabell; Ohtani, Shoichiro; Turner, Nicholas C.; Zambelli, Stefania; Harbeck, Nadia; André, Fabrice; Dent, Rebecca; Zhou, Xuan; Karantza, Vassiliki; Mejia, Jaime; Cortés, Javier

doi:10.1016/s1470-2045(20)30754-3

Cited by 314 publications

(300 citation statements)

References 25 publications

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“…First, the cell patterns in which the assessment is evaluated differ from trials to trials. For example, KEYNOTE-119 is a phase III clinical trial, which used pembrolizumab as monotherapy vs. single-agent chemotherapy in advanced breast cancer setting (Winer et al, 2021) Previous studies have confirmed that high tumor-infiltrating lymphocytes (TILs) were associated with response to PD-1/PD-L1 inhibitors in patients with breast cancer and a quantitative evaluation of TILs is important for any PD-L1 assay evaluation especially for breast cancer (Duchnowska et al, 2016;Hendry et al, 2017;Gonzalez-Ericsson et al, 2020). In this meta-analysis, we found that studies conducted by Rugo, 2018, andNanda, 2016, assessed PD-L1 expression only in tumor cells, while the other four studies assessed that in both tumor cells and immune cells.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Anti-PD-1/ PD-L1 Monotherapy for Metastatic Breast Cancer: Clinical Evidence

Zhang

Wang

et al. 2021

Front. Pharmacol.

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Background: Success has been reported in PD-1/PD-L1 blockade via pembrolizumab, atezolizumab, or avelumab monotherapy in manifold malignancies including metastatic breast cancer. Due to lack of large-scale study, here we present interim analyses to evaluate the safety and efficacy of these promising strategies in patients with advanced breast cancer.Methods: Six studies including 586 advanced breast cancer patients treated with anti-PD-1/PD-L1 monotherapy agents before July 1, 2020, were included. The anti-PD-1/PD-L1 agents include pembrolizumab, atezolizumab, land avelumab. Statistics was analyzed by R software and IBM SPSS Statistics 22.Results: Global analysis showed that for this monotherapy, the complete response was 1.26%, partial response was 7.65%, objective response rate (ORR) was 9.85%, and disease control rate (DCR) was 18.33%. 1-year overall survival rate and 6-month progression-free survival rate were 43.34 and 17.24%. Overall incidence of adverse events (AEs) was 64.18% in any grade and 12.94% in severe grade, while the incidence of immune-related AEs (irAEs) was approximately 14.75%: the most common treatment-related AEs of any grade that occurred in at least 5% of patients were arthralgia and asthenia; the most common severe treatment-related AEs occurred in at least 1% of patients were anemia and autoimmune hepatitis; the most common irAEs were hypothyroidism. Besides, the incidence of discontinue and death due to treatment-related AEs was about 3.06 and 0.31%, respectively. Additionally, by comparing efficacy indicators between PD-L1–positive and PD-L1–negative groups, an implicated correspondence between efficacy and the expression of PD-L1 biomarker was found: the PR was 9.93 vs 2.69%; the ORR was 10.62 vs. 3.07%; the DCR was 17.95 vs. 4.71%.Conclusion: Anti–PD-1/PD-L1 monotherapy showed a manageable safety profile and had a promising and durable anti-tumor efficacy in metastatic breast cancer patients. Higher PD-L1 expression may be closely correlated to a better clinical efficacy.

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Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Anti-PD-1/ PD-L1 Monotherapy for Metastatic Breast Cancer: Clinical Evidence

Zhang

Wang

et al. 2021

Front. Pharmacol.

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“…Nevertheless, higher ORR was achieved in patients with combined positive score (CPS) ≥10 and CPS ≥1. In an exploratory analysis, patients with a CPS ≥20 seemed to have lower risk of death in the pembrolizumab arm, with an increase in OS (14.9 vs. 12.5 months), and longer maintained responses, but no statistically significant improvement in PFS (3.4 vs. 2.4 months) [36].…”

Section: Ici As Single-agent In Metastatic Tnbcmentioning

confidence: 93%

Immune Check-Point Inhibitors in Breast Cancer: Current Evidence and Future Directions

Mosteiro¹,

Cejuela²,

Pernas³

2021

austinjsurg

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Check-point inhibitors have erupted as a treatment option for numerous kinds of neoplasms. Although there have been some achievements, the evidence supporting their use in breast cancer is scarce. Combinations with chemotherapy seem to provide better outcomes, and triple negative is the subtype most likely to benefit from them. New combination strategies are undergoing research to improve these results. Other approaches to determining biomarkers that identify which populations clearly benefit from these therapies are needed. Here, we review the clinical data of the role of immune check-point inhibitors in early and advanced breast cancer and present emerging strategies.

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“…However, in tumors classified as PD-L1 positive, a trend toward improved OS was noted, particularly as PD-L1 enrichment increased. Furthermore, for patients with tumors classified by CPS ≥10, OS was 12.7 months with pembrolizumab versus 11.6 months with chemotherapy, compared to 9.9 months with pembrolizumab versus 10.8 months with chemotherapy for the overall population [ 6 ]. Given these results, pembrolizumab as monotherapy is not recommended as a second- or third-line treatment for metastatic TNBC.…”

Section: Immune Checkpoint Inhibitors As Monotherapymentioning

confidence: 99%

Checkpoint inhibitor therapy for metastatic triple-negative breast cancer

Heeke

Tan

2021

Cancer Metastasis Rev

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Immunotherapy has become a mainstay of cancer treatment in many malignancies, though its application in breast cancer remains limited. Of the breast cancer subtypes, triple-negative breast cancers (TNBCs) are characterized by immune activation and infiltration and more commonly express biomarkers associated with response to immunotherapy. Checkpoint inhibitor therapy has shown promising activity in metastatic TNBC. In 2019, the US FDA granted accelerated approval of atezolizumab, a programmed death-ligand 1 (PD-L1) inhibitor, in combination with nab-paclitaxel for unresectable locally advanced or metastatic PD-L1-positive TNBC, based on the results of the phase III IMpassion130 trial. In 2020, the FDA also granted accelerated approval of pembrolizumab, a PD-1 inhibitor, in combination with chemotherapy for locally recurrent unresectable and metastatic PD-L1-positive TNBC, based on results of the phase III KEYNOTE-355 trial. Additional combination strategies are being explored in the treatment of metastatic TNBC, with the goal of augmenting antitumor activity. In this review, the clinical development of checkpoint inhibitors in the treatment of metastatic TNBC will be discussed, including clinical outcomes with monotherapy and combination therapy regimens, biomarkers that may predict for benefit, and future directions in the field.

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Pembrolizumab versus investigator-choice chemotherapy for metastatic triple-negative breast cancer (KEYNOTE-119): a randomised, open-label, phase 3 trial

Cited by 314 publications

References 25 publications

Efficacy and Safety of Anti-PD-1/ PD-L1 Monotherapy for Metastatic Breast Cancer: Clinical Evidence

Efficacy and Safety of Anti-PD-1/ PD-L1 Monotherapy for Metastatic Breast Cancer: Clinical Evidence

Immune Check-Point Inhibitors in Breast Cancer: Current Evidence and Future Directions

Checkpoint inhibitor therapy for metastatic triple-negative breast cancer

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