Combination therapy with nivolumab and bevacizumab appeared to have clinical activity in ovarian cancer patients with platinum-sensitive or platinum-resistant disease, with no new safety concerns, according to the results of a single-arm, phase II trial recently published in JAMA Oncology.
The trial enrolled 38 women with relapsed ovarian cancer, 18 of whom had platinum-resistant disease and 20 of whom had platinum-sensitive disease, from the Dana-Farber Cancer Institute and Massachusetts General Hospital. All of the women received nivolumab and bevacizumab intravenously once every two weeks.
The study population had a median age of 63.0 years (standard deviation, 9.1 years), according to the findings. Most patients had grade 3 (50%) or 4 cancer (34.2%) and most had tumors that were of a serous histologic subtype (60.5%) or adenocarcinoma histologic subtype (26.3%). Among the 31 patients with known germline BRCA status, 2 had pathogenic germline mutations. Nearly two-thirds of patients (65.8%) had previously received bevacizumab, the data showed.
No complete responses were seen. Overall, 11 patients (28.9%) achieved a confirmed partial response, including 8 patients with platinum-sensitive disease and 3 patients with platinum-resistant disease. This translated to an overall confirmed response rate of 40% for patients with platinum-sensitive disease and 16.7% for patients with platinum-resistant disease. One patient with platinum-sensitive disease achieved an unconfirmed partial response.
The trial was “unusual” because both patients with platinum-resistant disease and platinum-sensitive disease were included, said Konstantin Zakashansky, MD, Director of Gynecologic Oncology, Mount Sinai West, Associate Professor Obstetrics, Gynecology and Reproductive Science, the Icahn School of Medicine at Mount Sinai, in an interview with CancerNetwork.
“You don't usually mix them together,” he said.
As a result, Zakashansky added, one must be “very careful” when interpreting overall response because responses can vary “dramatically,” depending on whether its for platinum-sensitive or platinum-resistant disease.
“They aren’t phenomenal responses,” he explained. “But it’s better than what we see, especially in the platinum-resistant setting, where we really don’t have a lot of great options.”
Zakashansky said that in general, for the platinum-resistant setting, a response rate of 15 or 20 percent is considered a “very” good response. “That’s sort of similar to what you see in here.” However, he said, “if you look at platinum-sensitive disease, we do see complete responses, and not so much here.”
As for the safety profile of the combination, the majority of patients (89.5%) had 1 or more treatment-related adverse effect, according to the study. Overall, 9 patients (23.7%) had grade 3 or higher treatment-related adverse effects and 3 grade 4 events occurred, including 1 serum amylase level increase and 2 serum lipase level increases. The serum lipase level increases were believed to be due to nivolumab. No patients had a grade 5 event, the data showed.
Fatigue (47.4%), headache (28.9%), myalgia (28.9%), serum amylase level increase (28.9%), aspartate aminotransferase level increase (26.3%), and hypertension (26.3%) were the most frequently observed adverse effects, the authors added.
Zakashansky noted that the safety data revealed nothing that was unexpected and that the drugs did not appear worse when used in combination compared with when used as individual drugs.
Liu JF, Herold C, Gray KP, et al. Assessment of Combined Nivolumab and Bevacizumab in Relapsed Ovarian Cancer: A Phase 2 Clinical Trial. JAMA Oncol. Published online October 10, 2019. doi:10.1001/jamaoncol.2019.3343