Cabazitaxel shows a consistently greater survival benefit compared to mitoxantrone in patients with mCRPC

Cel. Niniejsza analiza — wtórna do badania TROPIC — ma na celu ocenę czasu przeżycia całkowitego (overall survival, OS) po zastosowaniu kabazytakselu w podgrupach chorych, u których od początku nie uzyskano odpowiedzi na docetaksel (D) i odstawiono docetaksel D z powodu progresji choroby, oraz u chorych, u których uzyskano początkowo odpowiedź na D, lecz u których wystąpiła progresja nowotworu w czasie < 3 miesiące od ostatniej dawki D. U takich pacjentów uzyskanie korzyści z ponownego leczenia D jest mało prawdopodobne, dlatego też potrzebują oni nowych opcji terapeutycznych, takich jak kabazytaksel. Metody. Z 755 chorych z przerzutami raka gruczołu krokowego opornego na kastrację (metastatic castration-resistant prostate cancer, mCRPC), włączonych do badania TROPIC, u 362 (47,9%) nie zaobserwowano początkowej odpowiedzi na D i przerwano jego podawanie. U 155 (20,5%) — w ocenie badacza — obserwowano początkowo od­powiedź na leczenie D, lecz wystąpiła progresja w czasie < 3 miesiące od ostatniej dawki D, a 238 (31,5%) nie należało do żadnej z tych podgrup. Wszystkich pacjentów zrandomizowano do grup otrzymujących kabazytaksel w dawce 25 mg/m2 lub mitoksantron w dawce 12 mg/m2 podawanych dożylnie co 3 tygodnie oraz prednizon, przyjmowany doustnie w dawce 10 mg/dzień. Wyniki. W każdej z podgrup mediana czasu przeżycia całkowitego (OS) dla chorych otrzymujących kabazytaksel była zawsze większa niż w grupie otrzymującej mitoksantron. Największą korzyść wydłużenia czasu przeżycia całkowitego w porównaniu z grupą otrzymującą mitoksantron obserwowano w podgrupie chorych, u których początkowo zaob­serwowano odpowiedź na D, a następnie progresję w czasie < 3 miesiące od ostatniej dawki D {mediana 15,7 miesiąca w porównaniu z 11,6 miesiąca, współczynnik ryzyka HR (hazard ratio) 0,52; 95% przedział ufności CI (confidence interval) [0,35–0,76]}. Mediana czasu przeżycia wolnego od progresji była także znacząco lepsza w tej podgrupie w porównaniu z grupą otrzymującą mitoksantron (2,6 miesiąca w porównaniu z 1,4 miesiąca, HR 0,66 (0,48–0,91). Wniosek. Kabazytaksel w skojarzeniu z prednizonem wykazuje konsekwentnie korzystniejsze działanie na czas prze­życia w porównaniu z leczeniem mitoksantronem w skojarzeniu z prednizonem w każdej z podgrup, w szczególności u chorych, u których zaobserwowano odpowiedź na D zastosowany w pierwszej linii i u których doszło do progresji w czasie < 3 miesiące od ostatniej dawki D, a także u chorych bez początkowej odpowiedzi na D, którzy przerwali jego przyjmowanie w celu kontroli progresji choroby.Aim. This sub analysis of TROPIC study evaluates overall survival (OS) under cabazitaxel in patients who had no initial response to docetaxel (D ) and discontinued D for disease progression and those who initially responded to D but experienced disease progression < 3 months since last D dose. These patients are believed unlikely to benefit from D re-treatment and need new treatment options such as cabazitaxel. Methods. Of the 755 patients with metastatic castration-resistant prostate cancer (mCRPC) enrolled in TROPIC study, 362 (47.9%) had no initial response to D and discontinued it for disease progression, 155 (20.5%) had an initial response to D therapy according to investigator judgment but progressed < 3 months since last D dose and 238 (31.5%) did not belong to these two subgroups. All patients were randomized to receive cabazitaxel 25 mg/m2 or mitoxantrone 12 mg/m2 both every 3 weeks and prednisone 10 mg per os daily. Results. Median OS with cabazitaxel was consistently longer than with mitoxantrone in all subgroups. The highest survival benefit versus mitoxantrone was observed for patients who initially responded to D and then progres­sed < 3 months since last D dose (median OS 15.7 versus 11.6 months, Hazard ratio (HR) 0.52 [95% CI 0.35–0.76]). Median PFS was also significantly improved in the latter subgroup compared to mitoxantrone (2.6 versus 1.4 months, HR 0.66 [0.48–0.91]). Conclusion. Cabazitaxel plus prednisone consistently shows a greater survival benefit compared to mitoxantrone plus prednisone whatever the subgroup considered, including responders to first-line D who progressed < 3 months since last D and pts without initial response to D who discontinued it for disease progression

Cost-Effectiveness of Alirocumab in Patients With Acute Coronary Syndromes: The ODYSSEY OUTCOMES Trial.

BACKGROUND: Cholesterol reduction with proprotein convertase subtilisin-kexin type 9 inhibitors reduces ischemic events; however, the cost-effectiveness in statin-treated patients with recent acute coronary syndrome remains uncertain. OBJECTIVES: This study sought to determine whether further cholesterol reduction with alirocumab would be cost-effective in patients with a recent acute coronary syndrome on optimal statin therapy. METHODS: A cost-effectiveness model leveraging patient-level data from ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was developed to estimate costs and outcomes over a lifetime horizon. Patients (n = 18,924) had a recent acute coronary syndrome and were on high-intensity or maximum-tolerated statin therapy, with a baseline low-density lipoprotein cholesterol (LDL-C) level ?70 mg/dl, non-high-density lipoprotein cholesterol ?100 mg/dl, or apolipoprotein B ?80 mg/l. Alirocumab 75 mg or placebo was administered subcutaneously every 2 weeks. Alirocumab was blindly titrated to 150 mg if LDL-C remained ?50 mg/dl or switched to placebo if 2 consecutive LDL-C levels were <15 mg/dl. Incremental cost per quality-adjusted life-year (QALY) was determined with the addition of alirocumab versus placebo and, based on clinical efficacy findings from the trial, was stratified by baseline LDL-C levels ?100 mg/dl and <100 mg/dl. RESULTS: Across the overall population recruited to the ODYSSEY OUTCOMES trial, using an annual treatment cost of US$5,850, the mean overall incremental cost-effectiveness ratio was US$92,200 per QALY (base case). The cost was US$41,800 per QALY in patients with baseline LDL-C ?100 mg/dl, whereas in those with LDL-C <100 mg/dl the cost per QALY was US$299,400. Among patients with LDL-C ?100 mg/dl, incremental cost-effectiveness ratios remained below US$100,000 per QALY across a wide variety of sensitivity analyses. CONCLUSIONS: In patients with a recent acute coronary syndrome on optimal statin therapy, alirocumab improves cardiovascular outcomes at costs considered intermediate value, with good value in patients with baseline LDL-C ?100 mg/dl but less economic value with LDL-C <100 mg/dl. (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab [ODYSSEY OUTCOMES]; NCT01663402)

High-Strength Copper/Silver Alloys Processed by Cold Spraying for DC and Pulsed High Magnetic Fields

International audienceHigh-strength, high-conductivity copper/silver-alloyed materials were prepared by cold-spray (CS) manufacturing. For DC high-field application at room temperature, bulk Cu/Ag (5% vol. Ag) alloys with high mechanical properties and high electrical conductivity can be obtained by CS and post-heat treatments. For pulsed-field application at liquid nitrogen temperature, bulk Cu/Ag (5% vol. Ag) alloys serve as precursors for room-temperature wire drawing. The Cu/Ag-alloyed bulk CS deposit presents a high yield strength of about 510 MPa with a corresponding electrical resistivity of 1.92 µΩ·cm (at 293 K). The Cu/Ag-alloyed wires show a very high ultimate tensile strength (1660 MPa at 77 K or 1370 MPa at 293 K) and low electrical resistivity (1.05 µΩ·cm at 77 K or 2.56 µΩ·cm at 293 K). Microstructural studies via STEM allow us to understand this very high level of mechanical strength. The results evidence that materials developed by CS exhibit very high mechanical properties compared to materials prepared by other routes, due to the high velocity of the deposited particles, which leads to high initial deformation rates and specific microstructural features

Formation processes of the ω-Al 70 Cu 20 Fe 10 phase synthesized by SPS technique

International audienc

Aflibercept Plus FOLFIRI vs. Placebo Plus FOLFIRI in Second-Line Metastatic Colorectal Cancer: a Post Hoc Analysis of Survival from the Phase III VELOUR Study Subsequent to Exclusion of Patients who had Recurrence During or Within 6 Months of Completing Adjuvant Oxaliplatin-Based Therapy

The aim of this post hoc analysis of the VELOUR study (ClinicalTrials.gov NCT00561470) was to investigate the treatment effect of adding aflibercept to second-line infusional 5-fluorouracil (5-FU), leucovorin and irinotecan (FOLFIRI) in patients with metastatic colorectal cancer (mCRC) who had failed any prior oxaliplatin-containing regimen. Adjuvant rapid relapsers (ARR), who were enrolled directly following relapse during or within 6 months of completion of oxaliplatin-containing adjuvant chemotherapy (N = 124, including 17 patients who also received bevacizumab as part of their adjuvant therapy), were excluded from the original VELOUR intention-to-treat (ITT) population (N = 1226). After exclusion of the ARR, overall survival (OS) in the ITT minus ARR (ITT-ARR) population (N = 1102) was longer in the aflibercept plus FOLFIRI arm than in the placebo plus FOLFIRI arm [hazard ratio (HR) 0.78, 95 % confidence interval (CI) 0.68-0.90; median survival difference 1.87 months]. In the subgroup of patients assigned to the prior bevacizumab stratum at randomization, OS was numerically longer in the aflibercept plus FOLFIRI arm than in the placebo plus FOLFIRI arm (HR 0.81; 95 % CI 0.63-1.04; median survival difference 2.14 months). Comparison of the post hoc analysis results with the primary analysis from VELOUR suggests that the inclusion of the directly enrolled ARR may have understated the aflibercept treatment benefit for both bevacizumab-pretreated and bevacizumab-naïve patients in the strictly second-line setting although no definitive conclusion may be inferred. The benefit associated with the addition of aflibercept to second-line FOLFIRI in patients with mCRC was observed whatever the timing of first-line disease progression. There were no unexpected safety concerns