Where Does Immune Checkpoint Inhibition Fit in Advanced Ovarian Cancer Treatment?

January 29, 2019

Researchers studied how the anti–PD-L1 agent avelumab fit into the recurrent and refractory ovarian cancer treatment landscape.

A phase I trial found promising antitumor activity and acceptable toxicity with the anti–PD-L1 agent avelumab in heavily pretreated patients with recurrent or refractory ovarian cancer. Several trials are now underway combining this agent with other types of systemic therapy.

“Standard therapies for platinum-resistant or refractory ovarian cancer, including pegylated liposomal doxorubicin, weekly paclitaxel, and topotecan, provide limited benefits, and overall survival in patients with relapsed disease who have received multiple lines of prior treatment is particularly short,” wrote study authors led by Mary L. Disis, MD, of the University of Washington School of Medicine in Seattle. “Increasing evidence indicates that immune responses may influence patient outcomes in ovarian cancer.”

The new study involved an expansion cohort from the phase I JAVELIN Solid Tumor trial, including a total of 125 patients with advanced ovarian cancer who had previously received chemotherapy including a platinum agent. Patients were treated with the anti–programmed death ligand 1 (PD-L1) agent avelumab at a dose of 10 mg/kg every 2 weeks. The results were published in JAMA Oncology.

The median follow-up period was 26.6 months. The median patient age in the trial was 62.0 years, and the median time since first diagnosis was 4.0 years. (Time since diagnosis of metastatic disease was 2.4 years.) Patients had received a median of 3 prior lines of therapy, with more than 40% receiving 4 or more lines of therapy. Among 46 patients for whom BRCA mutation status was known, 38 were mutation-negative and 8 were mutation-positive.

There was 1 complete response in the study (0.8%), along with 11 partial responses (8.8%), and 53 patients had stable disease (42.4%); this yielded an objective response rate of 9.6% and a disease control rate of 52.0%. The median time to response was 8.9 weeks, and the median duration of response was 10.4 months, with 5 patients in an ongoing response at the time of data cutoff. The authors noted that responses “occurred in patients irrespective of tumor PD-L1 status, with no notable trends.”

The median progression-free survival was 2.6 months, and the 6-month rate was 16.1%; at 12 months, the rate was 10.2%. The median overall survival was 11.2 months, with a 12-month rate of 47.0%.

Most of the cohort (97.6%) had at least 1 adverse event of any grade, and 68.8% of the cohort had a treatment-related adverse event of any grade. The most frequent such adverse events included infusion-related reactions (20.0%), fatigue (13.6%), and diarrhea (12.0%). Nine patients (7.2%) experienced a grade 3 or 4 treatment-related adverse event. Immune-related adverse events occurred in 16.8% of patients. A total of 14 patients (11.2%) had an adverse event that led to death, but none of these were deemed to be treatment-related.

“Although response and survival findings with avelumab monotherapy in this study are encouraging, it would be of interest to determine whether efficacy can be increased through combination or sequential regimens involving chemotherapy or PARP inhibitors,” the authors wrote.

Franco Muggia, MD, of New York University Langone Medical Center, who was not involved in the research, told Cancer Network that this was the largest trial to date involving an immune checkpoint inhibitor in this heavily pretreated recurrent ovarian cancer population. “The results show only modest activity” based on response rates, he said, but added that the data suggest that a number of patients did experience benefit. “Interest in integrating it with chemotherapy prior to drug-resistant recurrences, and with PARP inhibitors, has been generated, and there are several randomized trials ongoing that will hopefully define a role for such immune interventions that have already claimed impressive successes against other malignancies,” he noted.