Previous analysis of COMBI-d (NCT01584648) demonstrated improved progression-free survival (PFS) and overall survival (OS) with combination dabrafenib and trametinib versus dabrafenib monotherapy in ...BRAF V600E/K-mutant metastatic melanoma. This study was continued to assess 3-year landmark efficacy and safety after≥36-month follow-up for all living patients.
This double-blind, phase 3 study enrolled previously untreated patients with BRAF V600E/K-mutant unresectable stage IIIC or stage IV melanoma. Patients were randomized to receive dabrafenib (150mg twice daily) plus trametinib (2mg once daily) or dabrafenib plus placebo. The primary endpoint was PFS; secondary endpoints were OS, overall response, duration of response, safety, and pharmacokinetics.
Between 4 May and 30 November 2012, a total of 423 of 947 screened patients were randomly assigned to receive dabrafenib plus trametinib (n= 211) or dabrafenib monotherapy (n = 212). At data cut-off (15 February 2016), outcomes remained superior with the combination: 3-year PFS was 22% with dabrafenib plus trametinib versus 12% with monotherapy, and 3-year OS was 44% versus 32%, respectively. Twenty-five patients receiving monotherapy crossed over to combination therapy, with continued follow-up under the monotherapy arm (per intent-to-treat principle). Of combination-arm patients alive at 3 years, 58% remained on dabrafenib plus trametinib. Three-year OS with the combination reached 62% in the most favourable subgroup (normal lactate dehydrogenase and<3 organ sites with metastasis) versus only 25% in the unfavourable subgroup (elevated lactate dehydrogenase). The dabrafenib plus trametinib safety profile was consistent with previous clinical trial observations, and no new safety signals were detected with long-term use.
These data demonstrate that durable (≥3 years) survival is achievable with dabrafenib plus trametinib in patients with BRAF V600-mutant metastatic melanoma and support long-term first-line use of the combination in this setting.
Background
We aimed at investigating outcome of systemic treatments in advanced breast PT.
Methods
All cases of advanced breast PT treated with systemic treatments from 1999 to 2019, in one of the ...referral sarcoma centers involved in the study, were retrospectively reviewed.
Results
56 female patients were identified. Median age was 52 (range of 25–76) years. Patients received a median number of 2 systemic treatments (range of 1–4). Best responses according to RECIST were 1 (3.7%) CR, 11 (40.7%) PR, 6 (22.2%) SD, 9 (33.3%) PD with anthracyclines plus ifosfamide (AI); 2 (16.7%) PR, 4 (33.3%) SD, 6 (50.0%) PD with anthracycline alone; 3 (18.8%) PR, 4 (25.0%) SD, 9 (56.3%) PD with high-dose ifosfamide given as a continuous infusion (HD-IFX); 3 (20.0%) SD, 12 (80.0%) PD with a gemcitabine-based regimen (with 2 patients not evaluable); 1 (8.3%) PR, 2 (16.7%) SD, 9 (75.0%) PD with trabectedin (with 1 patient not evaluable); 1 (16.7%) PR, 1 (16.7%) SD, 4 (66.7%) PD with tyrosine-kinase inhibitors (TKI). The median PFS were 5.7 (IQR 2.5–9.1) months with AI; 3.2 (IQR 2.2–5.0) months with anthracycline alone; 3.4 (IQR 1.4–6.7) months with HD-IFX; 2.1 (IQR 1.4–5.2) months with gemcitabine-based chemotherapy; 1.8 (IQR 0.7–6.6) months with trabectedin; 3.4 (IQR 3.1–3.8) months with TKI. With a median follow-up of 35.3 (IQR 17.6–66.9) months, OS from the start of first-line systemic treatment was 15.2 (IQR 7.6–39.6) months.
Conclusion
In this series of advanced PT (to our knowledge, the largest reported so far), AI was associated with a high rate of responses, however, with a median PFS of 5.7 months. Other systemic treatments were poorly active.
The damage caused by the combination of corrosion and wear processes on the materials that machine elements are produced causes huge losses in several industries such as mineral processing, chemical, ...petrochemical and power generation. Some devices that operate in harsh environments, such as centrifugal pumps for transportation of caustic liquor used in the industries of production of aluminum, undergo a rapid deterioration of their materials by the coexistence of corrosion and erosion at temperatures around 75°C. The aim of this work is to study new ways for the corrosive–erosive problems confronted by the aluminum and nickel industries. Several coating materials in powder or wire form applied by GMA welding and HVOF thermal spray techniques are compared in erosion and erosion–corrosion tests. Corrosion tests were performed for comparison. A solution of 1M NaOH was used as a corrosive medium to get the polarization curves The temperature of the electrolyte was 25°C. For pure erosion test, the slurry erosive agent was 4l of water and an erosive particle concentration of 400g/l. Particles of ferric oxide, HRC=40–50 and an average diameter of 600μm, were used as an erosive agent. The impact angle of 90° was tested, with an impact velocity of the abrasive particles of 31m/s. Tests were performed for each condition at a time of 2h at intervals of 20min. The results show that the best performance was that of the mixed stainless steel and cobalt alloys welded coating even though the general resistance to erosive–corrosive wear significantly favors cermets in relation to the other welded deposits.
•We applied carbides and iron alloy coatings onto low carbon steel.•Six different coatings were evaluated in erosion and erosion–corrosion tests.•The erosion resistance of the different WC coatings applied by HVOF was similar.•The welded coatings combining iron and cobalt alloys presented the best results.•The performance of chromium carbide coating was the worst of all studied samples.
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