Immune Checkpoint Inhibitor-Induced LVEF Decreases Rare in Ovarian Cancer

Treatment with immune checkpoint inhibitors (ICIs) alone or combined with pegylated liposomal doxorubicin (PLD) or PLD alone did not lead to significant decreases in left ventricular ejection fraction (LVEF) in patients with ovarian cancer, according to cardiotoxicity data from the JAVELIN Ovarian 200 trial (ClinicalTrials.gov Identifier: NCT02580058).

The phase 3 study, was conducted to determine if avelumab alone or avelumab plus PLD improves outcomes in patients with platinum-resistant/platinum-refractory ovarian cancer compared with PLD alone. The primary endpoints of improved progression-free and overall survival were not met; however, LVEF was assessed in all patients using systemic and sequential cardiac monitoring. The researchers presented the LVEF data from this trial in The Oncologist.

In the trial, 566 patients with platinum-resistant/platinum-refractory ovarian cancer were randomly assigned 1:1:1 to receive avelumab alone (188 patients), avelumab plus PLD (188 patients), or PLD alone (190 patients). Cardiac monitoring was performed using echocardiography or multigated acquisition (MUGA) scans at baseline and every 8 weeks until discontinuation or end of treatment.

The median duration of treatment was 10.1 weeks in the avelumab only arm; 16.9 weeks for avelumab and 16.3 weeks for PLD in the combination arm; and 16 weeks in the PLD only arm. At baseline, 1 patient in the combination arm had an LVEF below the institutional lower limit of normal (LLN).

Grade 3 or higher cardiac adverse events (AEs) occurred in 4 (2.1%) patients in the avelumab only arm, 1 (0.5%) patient in the combination arm, and 0 patients in the PLD only arm.

LVEF decreases of 10% or more to below LLN at any time during treatment were observed in 1 (0.8%) patient in the avelumab only arm, 3 (1.9%) patients in the combination arm, and 2 (1.5%) patients in the PLD only arm. Four patients underwent subsequent assessment; any observed changes were transitory. No  cardiovascular AEs were related to LVEF decrease.

“In patients with preserved LVEF at baseline, significant LVEF decreases were rare with avelumab or PLD treatment alone or in combination,” the researchers wrote. “Observed changes in LVEF were transitory and were not associated with cardiovascular AEs. These findings align with the absence of increased cardiomyopathy or heart failure seen in other avelumab studies and the relatively low rate of cardiotoxicity with PLD treatment in ovarian cancer.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference
Bonaca MP, Moslehi JJ, Ledermann JA, et al. Left ventricular ejection fraction in patients with ovarian cancer treated with avelumab, pegylated liposomal doxorubicin, or both. Oncologist. Published online September 4, 2023. doi:10.1093/oncolo/oyad213