Left Ventricular Ejection Fraction in Patients With Ovarian Cancer Treated With Avelumab, Pegylated Liposomal Doxorubicin, or Both

Abstract

In the phase III JAVELIN Ovarian 200 trial, 566 patients with platinum-resistant/refractory ovarian cancer were randomized 1:1:1 to receive avelumab alone, avelumab plus pegylated liposomal doxorubicin (PLD), or PLD alone. Cardiac monitoring was included for all patients. We report left ventricular ejection fraction (LVEF) data from the trial. Grade ≥3 cardiac adverse events (AEs) occurred in 4 (2.1%), 1 (0.5%), and 0 patients in the avelumab, combination, and PLD arms, respectively. LVEF decreases of ≥10% to below institutional lower limit of normal at any time during treatment were observed in 1 (0.8%), 3 (1.9%), and 2 (1.5%) patients, respectively; 4 had subsequent assessments, and these showed transient decreases. No patient had a cardiovascular AE related to LVEF decrease. This analysis is, to our knowledge, the first analysis of LVEF in patients receiving immune checkpoint inhibitors. ClinicalTrials.gov Identifier NCT02580058.

Engineered Exosomes with ATF5-Modified mRNA Loaded in Injectable Thermogels Alleviate Osteoarthritis by Targeting the Mitochondrial Unfolded Protein Response

“…The FDA-approved thermosensitive hydrogels based on PLGA copolymers have been widely utilized to deliver therapeutic or bioactive drugs and have broad prospects. − The accumulation of metabolites derived from PLGA may elicit inflammatory response and expedite OA progression . However, certain studies did not observe a substantial inflammatory response induced by PLGA; thus, we believed that the local proinflammatory effects were weak and acceptable, which was confirmed in vivo and in vitro − Moreover, PEG has been widely used in clinical trials and confirmed its safety in vivo . − In vivo clinical trials of PLGA–PEG-PLGA are expected to fully confirm its safety and highlight the feasibility of widespread clinical application. Ex modAtf5 can be conveniently and evenly distributed in aqueous polymer solutions at RT.…”