Checkpoint Inhibitor Therapy for Metastatic Triple-Negative Breast Cancer

Immunotherapy has become a standard treatment for a variety of cancers, while its use in breast cancer is still limited. In triple-negative breast cancer (TNBC), infiltration and the expression of biomarkers linked to immunotherapy response are becoming more common.¹ The US Food and Drug Administration (FDA) has approved several immune checkpoint inhibitors (ICIs) to treat cancer in the recent decade, and there are numerous ongoing clinical trials evaluating the efficacy of next-generation immunotherapy drugs, novel indications, and combination therapies. The FDA gave atezolizumab, a monoclonal antibody, expedited approval in 2019. For unresectable locally advanced or metastatic cancer, a PD-L1 inhibitor in conjunction with nab-paclitaxel is used. The FDA also granted accelerated approval of pembrolizumab, a PD-1 inhibitor, in conjunction with chemotherapy for locally recurrent unresectable and metastatic PD-L1–positive TNBC in 2020.¹

Because of a lack of effective targeted medicines, TNBC is an aggressive breast cancer subtype with historically poor overall results. Chemotherapy has traditionally been the mainstay of treatment, while ICIs are currently being studied to determine if they can enhance patient outcomes.² In the treatment of patients with metastatic TNBC, further combination techniques are being investigated with the goal of enhancing anticancer efficacy. The clinical progress of ICIs in the treatment of patients with metastatic TNBC, including clinical results with monotherapy and combination therapy regimens, are all exciting areas of therapy for ICIs.

ICIs have shown modest response rates as monotherapy as well as improved results when used in combination with chemotherapy. ICIs showed better results in the first-line scenario and in immune-enriched tumors. Without targeted therapeutic options, metastatic TNBC is a difficult disease to treat. Conversely, the combination of chemotherapy and ICI therapy has shown considerable promise, especially in patients with immune-enriched tumors. In the MEDIOLA study, patients with metastatic breast cancer and a germline BRCA1/2 mutation were given a combination of the poly (ADP-ribose) polymerase inhibitor olaparib and durvalumab, an anti–PD-L1 monoclonal antibody.¹ The objective response rate was 63.3%, with the highest response rates (70%) when this combination was used as a first- or second-line treatment. Other targeted agents include cyclin-dependent kinase 4/6 inhibitors where combination studies are showing further promising results.¹

Overall, ICI clinical studies in patients with TNBC have shown promising results, particularly in the metastatic situation. ICI therapy is being studied in other combinations with cancer vaccines and even natural killer-cell treatment showing further promise for improving clinical outcomes in TNBC. Selecting patients who will most likely benefit from these treatments necessitates the development of reliable predictive biomarkers as well as a better understanding of cancer cell-intrinsic and microenvironmental factors that define a potent and long-lasting antitumor immune response.³

References

1. Heeke AL, Tan AR. Checkpoint inhibitor therapy for metastatic triple-negative breast cancer. Cancer Metastasis Rev. 2021;40:537-547.
2. Simmons CE, Brezden-Masley C, McCarthy J, et al. Positive progress: current and evolving role of immune checkpoint inhibitors in metastatic triple-negative breast cancer. Ther Adv Med Oncol. 2020;12:1758835920909091.
3. Thomas R, Al-Khadairi G, Decock J. Immune checkpoint inhibitors in triple negative breast cancer treatment: promising future prospects. Front Oncol. 2021;10:600573.