The cancer journal
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Immune checkpoint inhibition will be the first treatment breakthrough in recurrent and metastatic urothelial carcinoma since the introduction of combination chemotherapy more than 30 years ago. Monoclonal antibodies that target cytotoxic T-lymphocyte antigen 4, programmed death receptor 1, and programmed death receptor ligand 1 are furthest along in clinical development. Specific antibodies targeting either programmed death receptor 1 or programmed death receptor ligand 1 have demonstrated significant single-agent activity with impressive safety and tolerability for heavily pretreated patients in early-phase clinical trials. In our review, we discuss the rationale for immunotherapy in urothelial cancer, completed and ongoing studies with immune checkpoint therapy, the development of molecular subtypes of urothelial carcinoma with the potential impact of immunotherapy in these new groupings, and future directions of exploration with these agents in both early- and late-stage disease.
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Checkpoint-blocking antibodies have transformed cancer therapy, and the treatment of patients with metastatic melanoma has led the revolution. Herein, we review the current clinical data supporting the use of checkpoint-blocking antibodies in the treatment of melanoma and highlight outstanding clinical questions and unmet clinical needs.
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There is mounting evidence that the immune system plays an important role in the development and growth of gynecologic malignancies, and preliminary studies show activity of immune checkpoint inhibitors in ovarian, endometrial, and cervix cancer. In this review, we outline the completed trials of immune checkpoint blockade in the treatment of gynecologic malignancies. ⋯ The questions of which patients will benefit from immune checkpoint inhibitors and when immune checkpoint inhibitors should be incorporated into the treatment of gynecologic malignancies continue to be largely unanswered. As preclinical and clinical data emerge regarding predictive markers for response and resistance to immune checkpoint inhibitors, rational combination treatment strategies will help to further develop this emerging field in the treatment of gynecologic malignancies.
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Review Case Reports
Preclinical Rationale and Clinical Considerations for Radiotherapy Plus Immunotherapy: Going Beyond Local Control.
The use of radiation for cancer therapy has expanded and sparked interest in possible synergistic effects by combining it with current immunotherapies. In this review, we present a case of a patient who responded to programmed cell death 1 (PD1) blockade and radiation therapy and discuss possible mechanisms. ⋯ Clinical considerations are noted for combining radiation with immunotherapies to extend the benefit of immunotherapy to more patients. New trials are needed to appropriately investigate the best sequencing and radiation dose to prime an immune response and to identify predictive biomarkers of such responses.
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Immune checkpoint therapy has started a revolution in the field of oncology. The concept that the immune system plays a critical role in antitumor responses, which has been around for decades, has finally been proven and firmly established with elegant preclinical studies and dramatic clinical responses in patients as a result of antibodies that block inhibitory T-cell pathways. However, the clinical responses being achieved are only in a subset of patients, and more work is needed to provide a better understanding of the mechanisms that elicit tumor rejection, which will enable identification of appropriate biomarkers, reveal new targets, provide data to guide combination studies, and eventually dictate a platform that allows more patients to derive clinical benefit, including cures, with immune checkpoint therapy.