Checkpoint Inhibitors Induce Higher Rate of Adverse Events in Recurrent Ovarian Cancer

The use of immune checkpoint inhibitors in women with recurrent ovarian cancer has a clinical benefit but a higher rate of adverse events than previously reported in other tumor types.

The use of immune checkpoint inhibitors in women with recurrent ovarian cancer has a clinical benefit but a higher rate of adverse events (AEs) than previously reported in other tumor types, according to study findings presented during the 49th Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancers held in New Orleans March 24-27.

“There has been a rapid expansion in the use of checkpoint inhibition in many solid tumor types,” lead author Emily Hinchcliff, MD, The University of Texas MD Anderson Cancer Center in Houston, said. “The use of agents in ovarian cancer is still an area of active investigation both as monotherapy but also in combination with triple cytotoxic chemotherapy, targeted agents, or other immunologic effector modulation.”

The researchers examined women with recurrent disease who were being treated with an immune checkpoint inhibitor between January 2012 through August 2017. The main objective was to describe the clinical outcomes associated with this type of treatment. “We abstracted data including demographic, clinical and biologic factors and specifically were interested in the outcomes of response to therapy and immune-related adverse event,” she said.

The study included 44 women, who were predominately Caucasian (70.5%) and a majority had high-grade serous pathology. Median age was 53 years. About half of patients had platinum-sensitive disease at initial diagnosis.

The population of patients were highly treated with a median of 4 prior lines of therapy and as many as 10. “All patients treated in the clinical trials underwent somatic mutation testing prior to enrollment,” said Hinchcliff. “The mutation panel testing varied across the trials included, thus we analyzed a common subset of 50 genes.” The mean number of mutations was 2, with a range of 0 to 18.

The majority of patients (64%) were treated with a checkpoint inhibitor as part of a combination regimen and 36% received checkpoint inhibition as monotherapy. The combination regimens included checkpoint-checkpoint (21%), checkpoint plus other immune effector (46%), checkpoint plus targeted therapy (18%), and checkpoint plus traditional cytotoxic chemotherapy or radiation (14%).

The checkpoint targeted varied: anti-PD-1 was most common in 50% of women followed by anti-CTLA-4 and the combination of anti-PD-L1 and anti-CTLA-4.

The study found that of the 42 patients with data available, 13 patients (31%) progressed and 20 patients (48%) had initially stable disease. A partial response was seen in 6 patients (14%), and 3 of them experienced pseudo-progression.

Overall, immune checkpoint inhibitors demonstrated a response rate of 14% and stable disease rate of 48%.

Researchers only looked at grade 3 or 4 immune-related AEs. In 21 patients (48%), 28 AEs occurred and 14 patients (62%) who experienced an AE required a dose delay. Dermatologic, colitis, pulmonary, and cardiovascular AEs occurred, but the most common AEs were elevation in hepatic or pancreatic enzymes, which was seen in 6 patients (14%). “These rates are much higher than what has been previously reported in other tumor types,” said Hinchcliff.

To understand why, the researchers took a more detailed look at regimens received by patients and all, but 1, received checkpoint inhibitor as part of a combination regimen. Hinchcliff stated that 27% received combination checkpoint-checkpoint, specifically anti-PD-L1 and anti-CTLA4, and 64% received checkpoint plus some other immuno effector including IDL-1, anti-CSF-1R, or anti-TGF-beta.

“It is possible that there are tumor or histology-specific off-target effects of immune checkpoint inhibition that merit further investigation to aid in both prediction and prevention of such adverse events,” said Hinchcliff.

Hinchcliff EM, Hong D, Le H, et al. Adverse events and responses in patients with recurrent ovarian cancer undergoing early-phase immune checkpoint. Presented at: SGO Annual Meeting on Women’s Cancer; March 24-27, 2018. New Orleans. Abstract 15.

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