Anti-PD-1 Antibody Nivolumab Shows Activity in Ovarian Cancer

A small study found that treatment with the anti-PD-1 immunotherapy nivolumab was able to produce complete responses in patients with advanced platinum-resistant ovarian cancer. The phase II study of 20 patients had an overall response rate of 15% (3 responders); an additional 6 patients had stable disease.

The median progression-free survival time was 3.5 months and the median overall survival time was 20 months.

Results of the clinical trial are published in the Journal of Clinical Oncology.       

Patients were treated with nivolumab at either 1 mg/kg or 3 mg/kg every 2 weeks for up to 12 months. The two patients who experienced a complete response were in the 3 mg/kg cohort, including one patient with clear cell histology, which generally has a worse prognosis compared with serous adenocarcinoma.

Patients in the trial had a median age of 60 and were heavily pre-treated; 55% of patients (11 of 20) had received prior treatment with at least four regimens. Of the 20 patients, 15 had tumors with serous histology. The median duration of treatment with nivolumab was 3.5 months (range: 1–12 months).

High grade, treatment-related adverse events occurred in 40% of patients (8 of 20). The most common adverse events of any grade were increased serum AST, hypothyroidism, lymphocytopenia, decreased serum albumin, fever, increased serum ALT, maculopapular rash, arthralgia, arrhythmia, fatigue, and anemia.

Two patients had serious adverse events-disorientation and gait disorder and a 1-month long fever in one patient, and grade 3 fever and deep vein thrombosis in another patient.

Sixteen patients had high PD-L1 expression in their tumor specimens. While both patients who had a complete response had tumors with high PD-L1 expression, the correlation between expression and response was not significant. The authors noted that there may have been issues with the methods used for tumor sampling and PD-L1 expression, preventing the determination of whether PD-L1 is a potential marker of response in ovarian cancer patients.

Ovarian cancer is frequently diagnosed at a late stage and patients have few options besides surgery and platinum- and taxane-based chemotherapy. The rationale for an immunotherapy approach in this tumor type is that the cancer can elicit a spontaneous antitumor immune response and that ovarian tumors tend to express cancer-specific antigens.         

The National Cancer Institute is currently conducting a phase II study of nivolumab with or without another immunotherapy-the anti–CTLA-4 antibody ipilimumab-in 96 patients with advanced ovarian cancer.

Nivolumab is currently approved for the treatment of advanced melanoma and for the treatment of squamous non–small-cell lung cancer after progression on platinum-based chemotherapy.