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Single-agent nivolumab (Opdivo) did not improve overall survival (OS) or progression-free survival (PFS) versus chemotherapy for patients with platinum-resistant ovarian cancer, according to a randomized trial from Japan.

Both outcomes actually trended lower with the checkpoint inhibitor, as median OS was 10.1 months with nivolumab and 12.1 months with chemotherapy, and median PFS was significantly lower with nivolumab (2.0 vs 3.8 months). Response rate also favored chemotherapy, but patients had more durable responses with nivolumab.

The findings of the are consistent with a of single-agent pembrolizumab (Keytruda) and a phase III trial comparing single-agent avelumab (Bavencio), avelumab plus chemotherapy, and chemotherapy alone, reported Junzo Hamanishi, MD, PhD, of Kyoto University Graduate School of Medicine, and colleagues, in the .

Prior trials evaluating (Perjeta) and also showed no survival benefits versus chemotherapy for platinum-resistant ovarian cancer. A randomized comparison of chemotherapy with or without bevacizumab (Avastin) showed with the combination but no survival benefit.

"Collectively, these findings suggest that ovarian cancer may be resistant to checkpoint inhibitor monotherapy," Hamanishi and co-authors observed.

The authors of an agreed with the researchers' assessment of checkpoint inhibition for ovarian cancer.

"These negative results from the NINJA trial add to the growing list of trials demonstrating lack of activity of ICB [immune checkpoint blockade] in EOC [epithelial ovarian cancer]," stated Rebecca L. Porter, MD, PhD, and Ursula A. Matulonis, MD, both of Dana-Farber Cancer Institute in Boston.

"Although the data were negative for the overall population, [the fact that] the median DOR [duration of response] with nivolumab doubled indicated that the few patients who did respond to nivolumab had a durable response. Conversely, the response to chemotherapy in PROC [platinum-resistant ovarian cancer] tends to be short lived, underscoring the importance of identifying the small subset of patients who have a higher chance of benefiting from immunotherapy," Porter and Matulonis wrote.

Application of emerging technologies to characterize tumors and their microenvironment will lead to better biomarkers that will help optimize patient selection and improve clinical researchers' ability to test novel ICB combinations and sequences, the editorialists concluded.

The NINJA trial included 316 patients randomized to nivolumab or to physician's choice of gemcitabine or pegylated liposomal doxorubicin. The patients had a median age of about 59, about 80% had FIGO classification III or IV disease, and about a third had received three or more prior chemotherapy regimens. The primary endpoint was OS, and key secondary endpoints included PFS, objective response rate (ORR), and DOR.

The primary analysis revealed a trend toward better OS with chemotherapy, although the hazard ratio was 1.0 (95% CI 0.8-1.3, P=0.808). The nearly 2-month absolute difference in PFS in favor of chemotherapy did reach statistical significance (HR 1.5, 95% CI 1.2-1.9, P=0.002).

ORR favored chemotherapy (13.2% vs 7.6%) but the difference did not achieve statistical significance. Median DOR was more than twice as long with nivolumab (18.7 vs 7.4 months).

Treatment-related adverse events (TRAEs) occurred less often with nivolumab (61.5% vs 98.1%), and fewer patients randomized to the checkpoint inhibitor discontinued treatment because of TRAEs (7% vs 10%). The most common TRAEs in the nivolumab group were rash (10.3% of patients), fatigue (9.0%), and nausea (6.4%). Most common TRAEs in the chemotherapy group were decreased neutrophil count (64.%), decreased platelet count (33.5%), and nausea (32.9%).

A limitation of the study, the researchers said, was that it was not powered to detect treatment differences between subgroups.

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