scholarly journals Efficacy and Safety of Abemaciclib, an Inhibitor of CDK4 and CDK6, for Patients with Breast Cancer, Non–Small Cell Lung Cancer, and Other Solid Tumors

2016 ◽  
Vol 6 (7) ◽  
pp. 740-753 ◽  
Author(s):  
Amita Patnaik ◽  
Lee S. Rosen ◽  
Sara M. Tolaney ◽  
Anthony W. Tolcher ◽  
Jonathan W. Goldman ◽  
...  
2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A429-A429
Author(s):  
Elena Pentsova ◽  
Maria Düring ◽  
Charlotte Lybek Lind ◽  
John Rømer Nielsen

BackgroundLeptomeningeal metastasis (LM) from solid tumors may be diagnosed in approximately 10% of patients with metastatic cancer and can occur with virtually all malignant tumors. Median overall survival (OS) is poor and limited to a few months with LM-directed treatment, including available targeted therapy, immunotherapy and radiation therapy. Omburtamab specifically binds to B7-H3 (CD276), a transmembrane glycoprotein of the immunoglobulin superfamily. The limited expression of B7-H3 on normal cells, including normal brain, combined with the broad expression in various types of solid tumors, makes B7-H3 a target for radioimmunotherapy of LM from solid tumors. In this first-in-human trial the safety and efficacy of intracerebroventricular administration of radiolabeled omburtamab, 177Lu-DTPA-omburtamab, will be evaluated in patients with LM from ductal or lobular breast cancer, non-small cell lung cancer, or melanoma.MethodsThis is an open-label phase I/II study. Part 1 is a dose-escalation phase to be conducted at ~4 sites (US/Europe) with a primary objective of identifying the maximum tolerated dose and/or recommended phase II dose for Part 2 (RP2D). It will follow a 3+3 design with pts receiving up to five 5-week cycles of 177Lu-DTPA-omburtamab. Part 2 is a cohort-expansion phase at ~9 sites (US/Europe) in which a maximum of 48 patients in 3 cohorts (ductal or lobular breast cancer [cohort A], non-small cell lung cancer [cohort B], and melanoma [cohort C]) with up to 16 patients in each will receive up to five 5 week cycles of treatment with intracerebroventricular 177Lu DTPA omburtamab at the RP2D determined in Part 1. The primary objective of Part 2 is to establish the safety of repeat doses of 177Lu-omburtamab. Additional objectives of Parts 1/2 include the evaluation of absorbed radiation doses, PK profile, investigator-assessed response, duration of response, progression-free survival, and OS. Key inclusion criteria include diagnosis of either ductal or lobular breast cancer, non-small cell lung cancer, or malignant melanoma and diagnosis of recurrent or refractory LM; prior standard of care treatment of leptomeningeal disease; acceptable hematological, liver and kidney status; and a life expectancy of >2 months. The study has been approved by each institution’s ethics board, and patients provided informed consent before taking part.Trial RegistrationNCT04315246Ethics ApprovalThe study has been approved by each institution’s ethics board, and patients provided informed consent before taking part.


2019 ◽  
Vol 19 (3) ◽  
pp. 199-209 ◽  
Author(s):  
Bing-Di Yan ◽  
Xiao-Feng Cong ◽  
Sha-Sha Zhao ◽  
Meng Ren ◽  
Zi-Ling Liu ◽  
...  

Background and Objective: We performed this systematic review and meta-analysis to assess the efficacy and safety of antigen-specific immunotherapy (Belagenpumatucel-L, MAGE-A3, L-BLP25, and TG4010) in the treatment of patients with non-small-cell lung cancer (NSCLC). </P><P> Methods: A comprehensive literature search on PubMed, Embase, and Web of Science was conducted. Eligible studies were clinical trials of patients with NSCLC who received the antigenspecific immunotherapy. Pooled hazard ratios (HRs) with 95% confidence intervals (95%CIs) were calculated for overall survival (OS), progression-free survival (PFS). Pooled risk ratios (RRs) were calculated for overall response rate (ORR) and the incidence of adverse events. </P><P> Results: In total, six randomized controlled trials (RCTs) with 4,806 patients were included. Pooled results showed that, antigen-specific immunotherapy did not significantly prolong OS (HR=0.92, 95%CI: 0.83, 1.01; P=0.087) and PFS (HR=0.93, 95%CI: 0.85, 1.01; P=0.088), but improved ORR (RR=1.72, 95%CI: 1.11, 2.68; P=0.016). Subgroup analysis based on treatment agents showed that, tecemotide was associated with a significant improvement in OS (HR=0.85, 95%CI: 0.74, 0.99; P=0.03) and PFS (HR=0.70, 95%CI: 0.49, 0.99, P=0.044); TG4010 was associated with an improvement in PFS (HR=0.87, 95%CI: 0.75, 1.00, P=0.058). In addition, NSCLC patients who were treated with antigen-specific immunotherapy exhibited a significantly higher incidence of adverse events than those treated with other treatments (RR=1.11, 95%CI: 1.00, 1.24; P=0.046). </P><P> Conclusion: Our study demonstrated the clinical survival benefits of tecemotide and TG4010 in the treatment of NSCLC. However, these evidence might be limited by potential biases. Therefore, further well-conducted, large-scale RCTs are needed to verify our findings.


2019 ◽  
Vol 14 (10) ◽  
pp. S979-S980
Author(s):  
Y. Tanaka ◽  
T. Okano ◽  
Y. Kudo ◽  
S. Takeuchi ◽  
Y. Makino ◽  
...  

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