646 research outputs found
Critical appraisal of cabazitaxel in the management of advanced prostate cancer
No full textSumanta Kumar Pal1, Przemyslaw Twardowski1, Oliver Sartor21Division of Genitourinary Malignancies, Department of Medical Oncology and Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Los Angeles, CA, USA; 2Departments of Urology and Medicine, Tulane University School of Medicine, New Orleans, LA, USAAbstract: Docetaxel remains a cornerstone of therapy for the patient with metastatic castration-resistant prostate cancer (CRPC). However, the landscape of CRPC therapy is changing rapidly – recently, data from the phase III TROPIC study revealed a survival advantage with the novel taxane cabazitaxel/prednisone (compared with mitoxantrone/prednisone) in a cohort of 755 men with docetaxel-refractory metastatic CRPC. Interestingly, cabazitaxel bears substantial structural similiarity to docetaxel but appears to be mechanistically distinct. In preclinical studies, the agent has antitumor activity in a variety of docetaxel-refractory in vitro and in vivo models. Subsequent to phase I testing in advanced solid tumors (where neutropenia was identified as a dose-limiting toxicity), the agent was assessed in a phase II trial in advanced, taxane-refractory breast cancer and in the aforementioned phase III TROPIC study. This review describes in detail the preclinical and clinical development of cabazitaxel.Keywords: cabazitaxel, castration resistant prostate cancer, Jevtana, breast cancer, taxan
Updated overall survival in patients with prior checkpoint inhibitor therapy in the phase III TIVO-3 study
No full textBackground: The phase III TIVO-3 study demonstrated improvement in progression-free survival (PFS) with tivozanib compared with sorafenib in patients with 2-3 prior systemic regimens for metastatic renal cell carcinoma (mRCC). Methods: The TIVO-3 trial enrolled patients with measurable mRCC who had received 2 or more prior systemic therapies, including a vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI). Patients were stratified by International Metastatic RCC Database Consortium risk score and type of prior treatment and were randomized 1:1 to receive tivozanib or sorafenib. Efficacy was assessed using Response Evaluation Criteria in Solid Tumors version 1.1 criteria, with PFS as the primary endpoint. Safety was evaluated using Common Terminology Criteria for Adverse Events version v4.03, and statistical analyses included Cox regression for overall survival (OS) and descriptive statistics for duration of response (DOR). The current post-hoc long-term follow-up analysis consists of an assessment of OS in the previously stratified subpopulation of patients with prior CPI exposure. Results: Between May 2016, and August 2017, 350 patients were randomized, of which 26% had prior CPI exposure, with final analysis data cut off on June 21, 2021. In patients previously treated with CPIs (n = 91), the median PFS of tivozanib was 7.3 months versus 5.1 months with sorafenib and hazard ratio (HR) of 0.55 (95% CI, 0.32-0.94). The OS HR in the CPI-treated subset was 0.69 (95% CI, 0.43-1.11, P =.0992) favoring tivozanib, although with a median OS of 18.1 and 20.9 months, for tivozanib and sorafenib, respectively. Tivozanib demonstrated a longer median DOR of 20.3 versus 5.7 months for sorafenib in the subset previously treated with CPIs. The safety profile favored tivozanib, with lower rates of VEGF-TKI class-related grade ≥3 adverse events compared with sorafenib. However, in the subset of patients previously treated with CPIs, the incidence of grade ≥3 adverse events was higher, at 58% for tivozanib and 67% for sorafenib, compared with the ITT population, at 46% and 55%, respectively. Conclusions: In this long-term post-hoc update of the TIVO-3 trial, we show that in CPI-resistant mRCC, the PFS benefit of tivozanib over sorafenib is accompanied with improved OS data, although not statistically significant, and durable responses
Temporal Characteristics of Adverse Events of Tivozanib and Sorafenib in Previously Treated Kidney Cancer
No full textTivozanib showed improved progression free survival compared to sorafenib with less toxicity and better tolerability in patients with previously treated metastatic renal cell carcinoma. In this study we looked at most commonly reported adverse events, duration of toxicity, and characteristics of dose modifications. Our analysis showed that treatment related adverse events were less frequent, had longer onset, and shorter duration in tivozanib arm leading to less frequent dose modifications. Introduction: Tivozanib, vascular endothelial growth factor receptor inhibitor, met the primary endpoint of improved progression free survival compared to sorafenib in the phase 3 TIVO-3 study in patients with previously treated metastatic renal cell carcinoma. In this study we sought to understand the temporal characteristics of treatment related adverse events (TRAEs) and frequency and timing of the dose modifications. Materials and Methods: In this open label, randomized, phase 3 TIVO-3 study, previously treated patients with a diagnosis of metastatic renal cell carcinoma and with measurable disease were included. Patients were randomized to receive either tivozanib 1.5 mg orally once daily in 4-week cycles or sorafenib 400 mg orally twice daily continuously. Based on updated safety analysis data (cutoff date of August 15, 2019), time to onset of the most commonly reported TRAEs, duration of toxicity, rate of dose modifications was calculated for each treatment arm. Results: Overall, 350 patients were randomly assigned to receive tivozanib or sorafenib;173 patients from the tivozanib arm and 170 patients from the sorafenib arm were included in this analysis. Patients received a median of 11.9 cycles (336 days) and 6.7 cycles (192 days) of tivozanib and sorafenib, respectively. Dose reductions, interruptions and treatment discontinuations were 25%, 50%, and 21%, and 39%, 50%, and 30% in the tivozanib and sorafenib arms, respectively, with a longer time to onset of TRAEs in the tivozanib arm. Conclusion: Tivozanib was associated with less TRAEs, fewer dose modifications, a longer time to onset and a shorter duration of TRAEs compared to sorafenib
Tivozanib in Patients with Advanced Renal Cell Carcinoma Previously Treated With Axitinib: Subgroup Analysis from TIVO-3
No full textBackground In phase III TIVO-3 trial, tivozanib improved progression-free survival (PFS) compared to sorafenib for patients with metastatic renal cell carcinoma (mRCC). However, the effectiveness of this drug after exposure to other selective VEGFR agents has not yet been defined. Herein, we characterize the clinical efficacy of tivozanib in patients with mRCC previously treated with axitinib. Methods We identified patients from the intention to treat (ITT) population, in the TIVO-3 trial, who received treatment with axitinib before enrolment in the study and evaluated PFS, response rate (RR), and safety. Results Out of 350 patients, 172 (83:89, tivozanib:sorafenib) had received prior treatment with axitinib in TIVO-3. In this subgroup, PFS was 5.5 months with tivozanib and 3.7 months with sorafenib (HR 0.68). RR was 13% and 8% favoring tivozanib. Conclusions Tivozanib is active in the treatment of patients with mRCC who have progressed on prior therapies, including axitinib.Results of the TIVO-3 trial suggested that tivozanib has a progression-free survival advantage compared with sorafenib; however, it has been speculated that prior use of axitinib (which bears mechanistic resemblance to tivozanib) renders tivozanib less effective. This article examines the TIVO-3 dataset for outcomes of patients with prior axitinib therapy
Energy Efficient Array Initialization Using Loop Unrolling with Partial Gray Code Sequence
No full textMMI Coupler Based Miniature Electronically Controlled Photonic Switch on InGaAsP on Insulator Platform
No full textAbsorption spectrophotometric, fluorescence and theoretical investigations on supramolecular interaction of a designed bisporphyrin with C60 and C70
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