1. In a phase II clinical trial of 20 patients with platinum-resistant ovarian cancer, the use of nivolumab, a monoclonal antibody against programmed-death 1 (PD-1) receptor, demonstrated positive efficacy and tolerability.
Evidence Rating Level: 2 (Good)
Study Rundown: Due to its frequent diagnosis at advanced stages, ovarian cancer carries the highest mortality among all gynecologic malignancies. Previous reports have demonstrated that activation of the programmed cell PD-1 receptors in T-cells suppress cancer immune reactions and has been shown to be a negative prognostic factor in ovarian cancer. Nivolumab, an anti-PD-1 receptor monoclonal antibody, may interfere with this pathway and improve the cancer immune response. The purpose of this phase II clinical trial was to evaluate the safety and antitumor effect of this novel agent in ovarian cancer patients.
The study recruited 20 women with platinum-resistant ovarian cancer and followed their clinical response to nivolumab at two different doses (1mg/kg or 3mg/kg) for a median duration of 11 months. At the conclusion of this small clinical trial, the best overall response rate was 15% with a disease control rate of 45%. In terms of safety, grade 3 and 4 adverse reactions occurred in 40% of patients; however, the majority of patients (19 of 20) were able to complete the treatment course. The patient cohort on the higher dose of nivolumab demonstrated higher efficacy without an increase in frequency of adverse events. The results of this phase II trial are encouraging and support the implementation of larger phase III trials to further assess the efficacy of nivolumab in platinum-resistant ovarian cancer.
Click to read the study in JCO
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In-Depth [randomized controlled trial]: This was a single-center, open-label, phase II clinical trial that enrolled 20 women with platinum-resistant advanced ovarian cancer that has failed previous platinum or taxane-based therapies. Patients were excluded if they had a previous history of anti-PD-1 antibody therapy or evidence of chronic immunosuppression. Overall, 20 patients were recruited and assigned sequentially to a low-dose cohort (1mg/kg) followed by the high-dose cohort (3mg/kg). The primary outcome was the best overall response (RR) as assessed by RECIST (Response Evaluation Criteria In Solid Tumors). Secondary end points were drug safety, adverse events, progression-free survival (PFS), overall survival (OS), and disease control rate. At the conclusion of the trial, the overall RR was 15% (95% CI: 3.2% to 37.9%) and the disease control rate was 45% (95% CI: 23.1% to 68.5%). Median PFS and OS were 3.5 months and 20 months, respectively. Grade 3 to 4 adverse events occurred in 40% of patients; however, 19 out of 20 patients completed treatment. There was no difference in adverse reaction rate between the low-dose versus high-dose cohort. The most common adverse events were transaminitis, thyroiditis, lymphocytopenia, fever, rash, arthralgia, arrhythmia, and fatigue.
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