Journal of the National Comprehensive Cancer Network : JNCCN
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J Natl Compr Canc Netw · Oct 2017
ReviewUrothelial Carcinoma of the Bladder and the Rise of Immunotherapy.
With the advent of platinum-based chemotherapy, survival rates for metastatic urothelial carcinoma have plateaued, giving way to the modern immunotherapy paradigm. Although immunotherapy as an effective treatment dates back to the live, attenuated bacillus Calmette-Guérin vaccine, the recent impact of immune checkpoint inhibitors targeting programmed death/programmed death-ligand 1 (PD-1/PD-L1) coupled with the promise of both anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibodies and indoleamine-2, 3-dioxygenase-1 (IDO-1) inhibitors have provided a resurgence. To date, pembrolizumab, a PD-1 inhibitor, has been granted full FDA approval based on its high antitumor activity, tolerability, and efficacy, with notable prolonged durable responses in the second-line setting. ⋯ Further expansion of immunotherapy will hinge in part on the ability to define responders versus nonresponders through the use of biomarkers like PD-L1 or mutational load. Clinical trials with immunotherapy for metastatic disease as single agents or in combination are ongoing. This review explores the rise of immunotherapy and presents the current treatments and challenges posed with development of biomarkers, and provides a summary of ongoing phase III clinical trials.
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Multigene testing is a complicated area, with advantages and disadvantages of testing for hereditary cancer syndromes. Currently, NCCN does not endorse routing multiplex testing outside of a research setting, and/or intensive genetic counseling regarding risks and benefits. The 2017 NCCN Clinical Practice Guidelines in Oncology for Genetic/Familial High-Risk Assessment: Breast and Ovarian and Colorectal provide suggestions for mutation carriers identified by panel tests.
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Colorectal cancer (CRC) is a leading cause of cancer-related mortality in the United States. Response rates to second- and third-line therapy for metastatic CRC (mCRC) remain low, and immunotherapy is an attractive strategy for treatment in these patients given generally better tolerability than conventional chemotherapy and the potential for long-lasting durable responses. ⋯ Despite this, a proportion of MSI-H and nearly all microsatellite stable disease will not respond to single-agent checkpoint inhibition, and clinical trials are ongoing to increase responses to immunotherapy in mCRC through both better patient selection and novel combinations of immunotherapeutic agents. This review will provide a focused update on the most compelling clinical results of immunotherapy in CRC to date, as well as a summary of current strategies being tested in clinical trials in increase responses to immunotherapy in CRC.