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      Skin autoimmunity might be associated with increased efficacy of atezolizumab in metastatic urothelial carcinoma: a case report

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          Atezolizumab is a monoclonal antibody immune checkpoint inhibitor that binds to programmed death ligand 1 to selectively prevent its interaction with programmed cell death-1 (PD-1) and B7.1 (CD80) receptors. We present a case of a 61-year-old man with metastatic urothelial carcinoma of the right ureter and urinary bladder. After gemcitabine/cisplatin as the first-line chemotherapy and surgery, the patient received atezolizumab 1200 mg i.v. q3w. Following the first atezolizumab administration, he noted vitiligo periorally, on his hands, legs, and the scalp. The patient’s overall survival (OS) of >26 months and continuing response to atezolizumab treatment is considerably better than median OS in the SAUL study of 8.7 months (IMvigor211-like patients’ OS 10.0 months). This case indicates that increased efficacy of atezolizumab can be associated with cutaneous immune related adverse events, reflecting the known Th17 polarization of these diseases and showing that individuals with cutaneous adverse events could benefit from PD-1 checkpoint blockade in the therapy of metastatic urothelial carcinoma.

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          Primary Results from SAUL, a Multinational Single-arm Safety Study of Atezolizumab Therapy for Locally Advanced or Metastatic Urothelial or Nonurothelial Carcinoma of the Urinary Tract

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            A Changing of the Guard: Immune Checkpoint Inhibitors With and Without Chemotherapy as First Line Treatment for Metastatic Non-small Cell Lung Cancer

            Inhibitory antibodies targeting programmed death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) have resulted in improved outcomes for many patients with metastatic non-small cell lung cancer in (NSCLC) in the second-line setting due to their ability to lead to prolonged anti-tumor immune responses. Combining these immunotherapies with platinum-based chemotherapy as first-line treatment has resulted in improved response rates and increased survival when compared to platinum-based chemotherapy alone. Certain patient populations may even benefit from immune checkpoint inhibitors as monotherapy in the first-line setting. The PD-1 inhibitor pembrolizumab is approved as monotherapy or in combination with platinum + pemetrexed for most newly diagnosed patients with metastatic NSCLC, excluding those with a targetable oncogene such as ALK and EGFR. The PD-L1 inhibitor atezolizumab is also approved in combination with bevacizumab + carboplatin + paclitaxel for the same population, with some parts of the world also approving this regimen for patients with ALK rearrangements or EGFR activating mutations. However, there are many other chemo-immunotherapy regimens that have been evaluated as initial treatment in metastatic NSCLC. Additionally, combinations of PD-1 axis inhibitors with cytotoxic T lymphocyte antigen-4 inhibitors have been examined, although none are yet approved. Here we review the clinical data in support of the current first-line approaches across histologies and biomarker subtypes, as well as highlight future research directions revealed by the current data.
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              Beyond PD-1 Immunotherapy in Malignant Melanoma

              For many years, the standard therapy for malignant melanoma was based mainly on surgical resection. Unfortunately, this treatment is curative only in the early localized stage of this malignancy. The metastatic stage of malignant melanoma still remains a huge therapeutic challenge. Despite the many new therapeutic options that have become available over the last years, there is a constant need for safer and more effective treatment modalities. There has been a dynamic development of various anti-cancer immunotherapies directed against new molecular targets. A number of clinical trials are currently being conducted to confirm their effectiveness and safety. In this review of the literature, we summarize the contemporary knowledge on promising new immunotherapies beyond the currently available treatment options for malignant melanoma, including oncolytic immunotherapy, selective inhibitors of indoleamine 2,3-dioxygenease, anti-PD-(L)1 (programmed death ligand 1) drugs, immune checkpoint protein LAG-3 antibodies, inhibitors of histone deacetylase (HDAC) and inhibitors of B7-H3.

                Author and article information

                Croat Med J
                Croat. Med. J
                Croatian Medical Journal
                Croatian Medical Schools
                December 2019
                : 60
                : 6
                : 552-555
                [1 ]Department of Internal Medicine, University of Zagreb School of Medicine, Zagreb, Croatia
                [2 ]Unit for Clinical Pharmacology Department of Internal Medicine, University Hospital Centre Zagreb, Zagreb, Croatia
                [3 ]Division for Genitourinary Tumors, Department of Oncology, University Hospital Centre Zagreb, Zagreb, Croatia
                [4 ]Department of Oncology, University of Zagreb School of Medicine, Zagreb, Croatia
                Author notes
                Correspondence to:
Robert Likić
University Hospital Centre Zagreb
Department of Internal Medicine
Unit of Clinical Pharmacology
Kišpatićeva 12
10000 Zagreb, Croatia
 robert.likic@ 123456mef.hr
                Copyright © 2019 by the Croatian Medical Journal. All rights reserved.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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