Abstract
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.
Highlights
The latest data showed that up to 30% of women with nonmetastatic, early-stage breast cancer at first diagnosis will develop distant metastatic disease and up to 6% of women diagnosed with breast cancer in the United States have metastatic disease at the time of their first visit (Gennari et al, 2005; Chia et al, 2007; Dafni et al, 2010; Waks and Winer, 2019)
There is promising development in the treatment of metastatic breast cancer (MBC) and an encouraging median overall survival time approaching to 24 months, known as an incurable and fatal disease subtype, advanced breast cancer still poses a vitally significant threat to the wellness of women all over the world (Greenberg et al, 1996; Kiely et al, 2011), making it a pressing priority to discover novel and effective approaches to improve overall survival and prognosis of patients who suffered from this dangerous disease
Programmed death-1 (PD-1)/ PD-L1 interactions were reported in breast cancer, and the expression of PD-1/PD-L1 was confirmed to be closely related to the effect of checkpoint inhibitors (Mittendorf et al, 2015; Salatino et al, 2018; Zhu et al, 2018)
Summary
The latest data showed that up to 30% of women with nonmetastatic, early-stage breast cancer at first diagnosis will develop distant metastatic disease and up to 6% of women diagnosed with breast cancer in the United States have metastatic disease at the time of their first visit (Gennari et al, 2005; Chia et al, 2007; Dafni et al, 2010; Waks and Winer, 2019). By combining with the B7 globulin family ligand PDL1, PD-1 is activated and subsequently limiting T-cell activity, prohibiting over-active autoimmunity and immunity (Ademuyiwa et al, 2012; Liu et al, 2013). Such interactions function differently in normal tissues and tumor cells: in normal tissues, by restricting inflammatory activities during infections, PD-1/PD-L1 interactions exert protection effect against excessive tissue damage (Wang et al, 2019); in tumor cells, such interaction resulted in immune exhaustion and downregulation of immune response (Loibl et al, 2021). 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
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