Japanese journal of clinical oncology
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Sarcomas are a heterogeneous group of malignancies of mesenchymal origin; their molecular and genomic mechanisms differ with regard to histology. These characteristics lead to the presentation of varied immunological profiles based on the tumor microenvironment. Various immunotherapies are considered for the treatment of sarcoma. ⋯ Although the sole use of immune checkpoint inhibitors provides limited efficacy, combined immunotherapy with immune checkpoint inhibitors or molecular target agents, especially antiangiogenic agents, has shown moderate results against some types of sarcoma, such as the alveolar soft part sarcoma. Several clinical trials utilizing immunotherapy, including T-cell receptor gene therapy and immune checkpoint inhibitors, in sarcomas are under progress. By clarifying the tumor microenvironment and biomarker-predictive capacity of immunotherapy in sarcomas, better clinical trials can be designed; this could lead to improved outcomes for immunotherapy in sarcoma.
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Jpn. J. Clin. Oncol. · Jan 2021
ReviewBrigatinib and lorlatinib: their effect on ALK inhibitors in NSCLC focusing on resistant mutations and central nervous system metastases.
Major issues in anaplastic lymphoma kinase-positive non-small cell lung carcinoma are acquired resistance against anaplastic lymphoma kinase inhibitors and control of central nervous system metastasis. The development of these inhibitors has changed therapeutic strategy in patients with advanced anaplastic lymphoma kinase-positive non-small cell lung carcinoma. Brigatinib and lorlatinib were designed to penetrate the blood-brain barrier and to inhibit resistant mutations against anaplastic lymphoma kinase inhibitors. ⋯ In addition, brigatinib improved progression-free survival compared with crizotinib in anaplastic lymphoma kinase inhibitor-naïve patients with anaplastic lymphoma kinase-positive non-small cell lung carcinoma. Lorlatinib has demonstrated clinical antitumour activity against both intracranial and extracranial lesions in patients with anaplastic lymphoma kinase- or c-ros oncogene 1 (ROS1)-positive non-small cell lung carcinoma. Ongoing trials and further studies of these agents' biological and clinical properties would provide insight into the optimal therapeutic strategy for administering them to achieve the best survival benefit.
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Jpn. J. Clin. Oncol. · Dec 2020
ReviewAdjuvant and neoadjuvant therapy for biliary tract cancer: a review of clinical trials.
Cancer originating in the biliary tract can be classified as bile duct cancer (cholangiocarcinoma), gallbladder cancer, or ampullary cancer. Bile duct cancer is further divided to intrahepatic, perihilar and distal bile duct subtypes according to the anatomical location of the tumor. The biological characteristics of each tumor are heterogeneous. ⋯ Several other studies of adjuvant therapy are ongoing, and they may lead to reforms in treatment strategy for resectable biliary tract cancer in the future. The use of neoadjuvant therapy for biliary tract cancer is in its infancy, but it is expected to overcome the limitations of adjuvant therapy for this malignancy. In this review, we summarized the evidence available from clinical trials of adjuvant and neoadjuvant therapy for biliary tract cancer and described ongoing clinical trials.
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The prognosis of multiple myeloma was quite poor in the last century, but it has significantly improved with the incorporation of novel agents, immunomodulatory drugs (IMiDs) and proteasome inhibitors. Thalidomide was first developed as a sedative in 1950s, but it was withdrawn from the market because of teratogenicity. In 1990s, however, thalidomide received attention due to the discovery of its anticancer potential derived from antiangiogenic and immunomodulatory activities, and its therapeutic effect on myeloma. ⋯ There are many clinical trials of multiple myeloma using IMiDs under various conditions, and most of them show the efficacy of IMiDs. Nowadays lenalidomide plays a central role in both newly diagnosed and relapsed/refractory settings, mainly in combination with other novel agents such as proteasome inhibitors and monoclonal antibodies. This review presents an overview of recent advances in immunomodulatory drugs in the treatment of multiple myeloma.
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In recent years, many antibody therapies for multiple myeloma have been developed. Antibodies against SLAMF7, CD38, B-cell maturation antigen and PD-1 have been developed and clinical trials are currently under way. As of July 2017, antibodies clinically available in Japan for the treatment of multiple myeloma are elotuzumab against SLAMF7 and daratumumab against CD38. ⋯ CD38 is expressed ubiquitously virtually in all tissues that are highly expressed on plasma cells and it represents an attractive target for immunotherapy using monoclonal antibodies. In the phase III CASTOR trial, patients treated with daratumumab+bortezomib+dexamethasone had a better CR rate and progression-free survival rate compared with bortezomib+dexamethasone-treated patients (29% vs 10%, median progression-free survival: 16.7 vs 7.1 months, respectively). Moreover, in the phase III POLLUX trial, patients treated with daratumumab+lenalidomide+dexamethasone had a better response and progression-free survival (CRR or better: 55% vs 23%, 30-month progression-free survival: 58% vs 35%), compared with lenalidomide+dexamethasone-treated patients.