Anti-NaPi2b antibody-drug conjugate lifastuzumab vedotin (DNIB0600A) compared with pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer in a randomized, open-label, phase II study.

Background: Lifastuzumab vedotin (LIFA) is a humanized anti-NaPi2b monoclonal antibody conjugated to a potent antimitotic agent, monomethyl auristatin E, which inhibits cell division by blocking the polymerization of tubulin. This study is the first to compare an antibody-drug conjugate (ADC) to standard-of-care in ovarian cancer (OC) patients. Patients and methods: Platinum-resistant OC patients were randomized to receive LIFA [2.4 mg/kg, intravenously, every 3 weeks (Q3W)] or pegylated liposomal doxorubicin (PLD) (40 mg/m2, intravenously, Q4W). NaPi2b expression and serum CA-125 and HE4 levels were assessed. The primary end point was progression-free survival (PFS) in intent-to-treat (ITT) and NaPi2b-high patients. Results: Ninety-five patients were randomized (47 LIFA; 48 PLD). The stratified PFS hazard ratio was 0.78 [95% confidence interval (95% CI), 0.46-1.31; P = 0.34] with a median PFS of 5.3 versus 3.1 months (LIFA versus PLD arm, respectively) in the ITT population, and 0.71 (95% CI, 0.40-1.26; P = 0.24) with a median PFS of 5.3 months versus 3.4 months (LIFA versus PLD arm, respectively) in NaPi2b-high patients. The objective response rate was 34% (95% CI, 22% to 49%, LIFA) versus 15% (95% CI, 7% to 28%, PLD) in the ITT population (P = 0.03), and 36% (95% CI, 22% to 52%, LIFA) versus 14% (95% CI, 6% to 27%, PLD) in NaPi2b-high patients (P = 0.02). Toxicities included grade ≥3 adverse events (AEs) (46% LIFA; 51% PLD), serious AEs (30% both arms), and AEs leading to discontinuation of drug (9% LIFA; 8% PLD). Five (11%) LIFA versus 2 (4%) PLD patients had grade ≥2 neuropathy. Conclusion: LIFA Q3W was well tolerated and improved objective response rate with a modest, nonstatistically significant improvement of PFS compared with PLD in platinum-resistant OC. While the response rate for the monomethyl auristatin E-containing ADC was promising, response durations were relatively short, thereby highlighting the importance of evaluating both response rates and duration of response when evaluating ADCs in OC. Clinical trials.gov: NCT01991210.

Orthodontic positioner used for home fluoride treatments.

It has been well documented that the more time the enamel surface is exposed to fluoride, the higher will be the caries protection. An extremely good method of greatly increasing caries resistance is by daily or weekly home fluoride treatments. This procedure is usually limited to special cases of rampant caries, patients with hemophilia, and handicapped patients in whom caries control is vital. It is not used more widely because of the added costs of impressions, tray fabrication, and professional. If the patient already has a vehicle for applying fluoride, such as a positioner or mouth guard, it is a simple matter to prescribe or dispense fluoride gel to be used when these appliances are being worn. This is expecially true for orthodontic postioners. When bands are removed, a slight space usually exists interproximally. This space greatly facilitates fluoride contact with the proximal surfaces. Fluoride will tend to recalcify decalcified areas of enamel in addition to providing added caries protection for the patient. If positioners are not used after band removal, home fluoride trays or rinses can also be effective. Since many orthodontic patients wear a positioner when bands are removed, the orthodontist can provide his patients with the benefits of topical fluoride by prescribing fluoride gel and explaining how to use it along with his positioner.