FDA Approval Summary: Lutetium Lu 177 Vipivotide Tetraxetan for Patients with Metastatic Castration-Resistant Prostate Cancer.

On March 23, 2022, the FDA approved Pluvicto (lutetium Lu 177 vipivotide tetraxetan, also known as 177Lu-PSMA-617) for the treatment of adult patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor pathway inhibition and taxane-based chemotherapy. The recommended 177Lu-PSMA-617 dose is 7.4 gigabecquerels (GBq; 200 mCi) intravenously every 6 weeks for up to six doses, or until disease progression or unacceptable toxicity. The FDA granted traditional approval based on VISION (NCT03511664), which was a randomized (2:1), multicenter, open-label trial that assessed the efficacy and safety of 177Lu-PSMA-617 plus best standard of care (BSoC; n = 551) or BSoC alone (n = 280) in men with progressive, PSMA-positive mCRPC. Patients were required to have received ≥1 androgen receptor pathway inhibitor, and one or two prior taxane-based chemotherapy regimens. There was a statistically significant and clinically meaningful improvement in overall survival (OS), with a median OS of 15.3 months in the 177Lu-PSMA-617 plus BSoC arm and 11.3 months in the BSoC arm, respectively (HR: 0.62; 95% confidence interval: 0.52-0.74; P < 0.001). The most common adverse reactions (≥20%) occurring at a higher incidence in patients receiving 177Lu-PSMA-617 were fatigue, dry mouth, nausea, anemia, decreased appetite, and constipation. The most common laboratory abnormalities that worsened from baseline in ≥30% of patients receiving 177Lu-PSMA-617 were decreased lymphocytes, decreased hemoglobin, decreased leukocytes, decreased platelets, decreased calcium, and decreased sodium. This article summarizes the FDA review of data supporting traditional approval of 177Lu-PSMA-617 for this indication.

Does 6 Hours of Contact With Alginate Impression Material Affect Dental Cast Properties?

Alginate impression (irreversible hydrocolloid) material is commonly used in dental practice because it is easy to mix, low in cost, and well tolerated by patients. The material is not dimensionally stable, however; thus, it is necessary to pour the impression immediately after the molding is accomplished, or within 60 minutes if the impression is kept in 100% humidity. Excessive contact of the alginate impression with the cast model over time may affect the model's properties. In this study, the authors tested the effect of contact time between an alginate impression and type III dental stone on cast model properties. Sixty-seven cast models were obtained from a stainless steel cylinder by using irreversible hydrocolloid impression material and type III dental stone. Thirty-seven cast models were separated from the impression after 1 hour (control group) and 30 cast models were separated after 6 hours (study group). The samples were evaluated under light microscope for surface details and measured by digital caliper for dimensional stability. An indentation on the cast was made and the depth of the indentation was then measured with a digital caliper to measure hardness. The dimensional stability of the cast models was not affected when contact time was increased from 1 hour to 6 hours (P = .507). Surface details did not deteriorate when contact time was increased, as all of the samples could reproduce all details after the 1-hour and 6-hour interval periods. However, hardness was greater after 1 hour of contact time (P = .001) than after 6 hours of contact time. In conclusion, contact between alginate impression material and type III dental stone up to 6 hours did not affect the dimensional stability and richness of the surface; hardness, though, was significantly affected.

FDA Approval Summary: Olaparib Monotherapy in Patients with Deleterious Germline BRCA-Mutated Advanced Ovarian Cancer Treated with Three or More Lines of Chemotherapy.

On December 19, 2014, the FDA approved olaparib capsules (Lynparza; AstraZeneca) for the treatment of patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. The BRACAnalysis CDx (Myriad Genetic Laboratories, Inc.) was approved concurrently. An international multicenter, single-arm trial enrolled 137 patients with measurable gBRCAm-associated ovarian cancer treated with three or more prior lines of chemotherapy. Patients received olaparib at a dose of 400 mg by mouth twice daily until disease progression or unacceptable toxicity. The objective response rate (ORR) was 34% with median response duration of 7.9 months in this cohort. The most common adverse reactions (≥20%) in patients treated with olaparib were anemia, nausea, fatigue (including asthenia), vomiting, diarrhea, dysgeusia, dyspepsia, headache, decreased appetite, nasopharyngitis/pharyngitis/upper respiratory infection, cough, arthralgia/musculoskeletal pain, myalgia, back pain, dermatitis/rash, and abdominal pain/discomfort. Myelodysplatic syndrome and/or acute myeloid leukemia occurred in 2% of the patients enrolled on this trial.

Effect of contact time between alginate impression and type III dental stone on cast model properties

Objective: To measure the effect of different contact time between the alginate impression and type III dental stone on cast model properties in the terms of dimension stability, hardness and surface details reproduction. Material and methods: Sixty-seven cast models were obtained from stainless steel cylinder using alginate impression material and type III dental stone. Thirty-seven cast models were separated after one hour (control group) and 30 cast models were separated from impressions after 9 hours. The samples were evaluated under light microscope for surface details, measured by digital caliper for dimension stability and hardness was tested by making indentation on the cast then measuring the depth using digital caliper. Results: The dimension stability of cast models was not affected by increasing contact time between type III dental stone and alginate impression while surface details decreased. In the meanwhile, hardness was improved with increasing contact time. Conclusion: According to the results of this study, pouring of impression up to 9 hours can negatively affect the cast model properties in the term of details richness.