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Therapeutic Associations Comprising Anti-PD-1/PD-L1 in Breast Cancer: Clinical Challenges and Perspectives.

ABSTRACT: Despite a few cases of long-responder patients, immunotherapy with anti-PD-(L)1 has so far proved rather disappointing in monotherapy in metastatic breast cancer, prompting the use of synergistic therapeutic combinations incorporating immunotherapy by immune-checkpoint inhibitors. In addition, a better understanding of both the mechanisms of sensitivity and resistance to immunotherapy, as well as the immunological effects of the usual treatments for breast cancer, make it possible to rationally consider this type of therapeutic combination. For several years, certain treatments, commonly used to treat patients with breast cancer, have shown that in addition to their direct cytotoxic effects, they may have an impact on the tumor immune microenvironment, by increasing the antigenicity and/or immunogenicity of a "cold" tumor, targeting the immunosuppressive microenvironment or counteracting the immune-exclusion profile. This review focuses on preclinical immunologic synergic mechanisms of various standard therapeutic approaches with anti-PD-(L)1, and discusses the potential clinical use of anti-PD-1/L1 combinations in metastatic or early breast cancer.

SUBMITTER: Ledys F

PROVIDER: S-EPMC8656936 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description: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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Therapeutic Associations Comprising Anti-PD-1/PD-L1 in Breast Cancer: Clinical Challenges and Perspectives.

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