Future oncology
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Since the US FDA-approval of the first immune checkpoint inhibitor, anticytotoxic T-lymphocyte antigen-4 monoclonal antibody ipilimumab, for metastatic melanoma on 28 March 2011, another six agents have been granted use among a multitude of tumors, including renal cell cancer, Hodgkin lymphoma, urothelial carcinoma and non-small-cell lung cancer. The first anti-programmed cell death ligand-1 monoclonal antibody to receive the FDA approval, atezolizumab (Tecentriq®), has yielded promising results among international Phase III trials in triple-negative breast cancer and small-cell lung cancer, expanding the field of cancer immunotherapies. Herein, we review the pharmacodynamic and pharmacokinetic properties of atezolizumab, its safety and efficacy data from early clinical trials and summarize data from Phase III IMpassion130 trial, prompting FDA and EMA approval of atezolizumab in metastatic triple-negative breast cancer. Finally, implications for clinical use and ongoing research will be briefly discussed.
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Chimeric antigen receptor (CAR) T-cell therapies are increasingly providing options for care of oncology patients with advanced hematologic malignancies, which has led to two US FDA approvals. However, they are often associated with significant immune related adverse events that require prompt management. These toxicities are mainly cytokine release syndrome and neurotoxicity, and can be managed in an appropriate setting when presenting to nononcologists or internists. ⋯ A management approach can be determined by the severity of the toxicity. Tocilizumab, a humanized monoclonal antibody, was FDA approved for the treatment of cytokine release syndrome, and corticosteroids may be used. Neurotoxicity is generally managed with supportive care and steroidal therapy.
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DC Bead is designed for the embolization of liver malignancies combined with local sustained chemotherapy delivery. It was first demonstrated around a decade ago that irinotecan could be loaded into DC Bead and used in a transarterially directed procedure to treat colorectal liver metastases, commonly referred to as drug-eluting bead with irinotecan (DEBIRI). Despite numerous reports of its safe and effective use in treating colorectal liver metastases patients, there remains a perceived fundamental paradox as to how this treatment works. This review of the mechanism of action of DEBIRI provides a rationale for why intra-arterial delivery of this prodrug from an embolic bead provides for enhanced tumor selectivity, sparing the normal liver while reducing adverse side effects associated with the irinotecan therapy.
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Aim: To identify whether PD-L1 expression and EGFR status are associated with response to treatment benefit in advanced non-small-cell lung cancer (NSCLC) patients receiving PD-1/PD-L1 inhibitors. Methods: The relevant studies were retrieved and systematic evaluation was conducted. Databases were searched until November 2018. ⋯ For patients with PD-L1 expression levels of ≥1%, overall response rates were significantly prolonged, but there was no difference in patients with PD-L1 expression levels of <1% (hazard ratio [HR]: 1.75; 95% CI: 0.87-3.52; p = 0.12). EGFR wild-type NSCLC patients could benefit from PD-1/PD-L1 inhibitors in PFS (HR: 0.65; 95% CI: 0.45-0.91; p = 0.01) and OS (HR: 0.67; 95% CI: 0.62-0.73; p < 0.00001). Conclusion: This study indicates that PD-L1-positive or EGFR wild-type advanced NSCLC patients might get potential benefit from PD-1/PD-L1 inhibitors.
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Meta Analysis
Gemtuzumab ozogamicin for treatment of newly diagnosed CD33-positive acute myeloid leukemia.
In September 2017, the US FDA announced re-approval of gemtuzumab ozogamicin (GO), a CD33-targeting immunoconjugate, for treatment of newly diagnosed and relapsed/refractory acute myeloid leukemia (AML). This is a very significant step toward defining new treatment regimens in AML, as the treatment has essentially stayed unchanged with the '7 + 3 induction regimen' (7 days cytarabine and 3 days of anthracycline) since 1973. ⋯ This review article discusses the challenges faced and lessons learned during the journey of GO for AML treatment. Selected trials that have made significant contribution in our understanding of the most efficacious and safe use of GO for treating AML patients as well as factors influencing GO response are highlighted in this article.