Efficacy and safety of nivolumab in Japanese patients with uterine cervical cancer, uterine corpus cancer, or soft tissue sarcoma: Multicenter, open‐label phase 2 trial

Abstract

Nivolumab is a human monoclonal antibody against the immune checkpoint receptor programmed death‐1, inhibiting binding to programmed death‐ligand 1 or 2 (PD‐L1 or PD‐L2). This phase 2 study evaluated the efficacy and safety of nivolumab in patients with advanced/recurrent uterine cervical cancer, uterine corpus cancer, or soft tissue sarcoma (STS). Patients received nivolumab 240 mg at 2‐week intervals. Primary endpoint was objective response rate; secondary endpoints included overall survival, progression‐free survival, and safety. PD‐L1 expression and microsatellite‐instability (MSI) status were analyzed as potential efficacy biomarkers. Objective response rate was 25%, 23%, and 0% in patients with cervical cancer (n = 20), corpus cancer (n = 22), and STS (n = 21), respectively. The lower 80% confidence intervals of objective response rates in patients with cervical or corpus cancer exceeded the threshold rate (5%); the primary endpoint was met in cervical and corpus cancer, but not in STS. Median progression‐free survival was 5.6, 3.4, and 1.4 months, and 6‐month overall survival was 84%, 73%, and 86% in cervical cancer, corpus cancer, and STS, respectively. The objective response rate was higher in patients with cervical cancer with PD‐L1‐positive (n = 5/15; 33%) versus PD‐L1‐negative (n = 0/5; 0%) tumors. The two patients with corpus cancer classified as MSI‐high responded; the six patients classified as microsatellite stable did not respond. Overall, nivolumab showed acceptable toxicity in all cohorts, with evidence of clinical activity in uterine cervical or corpus cancer, but not in STS. PD‐L1 expression in cervical cancer and MSI‐high in corpus cancer may predict clinical activity of nivolumab in these cancers.

Predictive Values of Programmed Cell Death-Ligand 1 Expression for Prognosis, Clinicopathological Factors, and Response to Programmed Cell Death-1/Programmed Cell Death-Ligand 1 Inhibitors in Patients With Gynecological Cancers: A Meta-Analysis

“…Additional 3 studies were supplemented through checking the references of reviews. Finally, 55 studies were eligible for the meta-analysis ( 16 – 70 ).…”

“…One thing should be noted that tumor cells and TICs were both analyzed and the different IHC counting methods (cut-off points) were applied in some studies, which led to more datasets used for analysis of the prognostic and clinical significance of PD-L1 compared with the actual number of papers ( Table S1 ). The patients in most of these studies underwent surgery, radiotherapy and/or chemotherapy with routine drugs, while six studies specifically explored the efficacy of anti-PD-1/PD-L1 antibodies (pembrolizumab, atezolizumab, nivolumab) for the treatment of gynecological cancers ( 65 – 70 ). The association of PD-L1 expression status with ORR, OS and PFS to these anti-PD-1/PD-L1 immune checkpoint inhibitors was also investigated in these six studies ( 65 – 70 ).…”

“…The patients in most of these studies underwent surgery, radiotherapy and/or chemotherapy with routine drugs, while six studies specifically explored the efficacy of anti-PD-1/PD-L1 antibodies (pembrolizumab, atezolizumab, nivolumab) for the treatment of gynecological cancers ( 65 – 70 ). The association of PD-L1 expression status with ORR, OS and PFS to these anti-PD-1/PD-L1 immune checkpoint inhibitors was also investigated in these six studies ( 65 – 70 ). The NOS scores of all included studies were > 6, suggesting the methodological quality was high for all of them ( Table S2 ).…”

Preoperative Neutrophil-to-Lymphocyte Ratio as a Prognostic Factor in Uterine Sarcoma

“…In addition, NLR has been recently highlighted as a prognostic factor for treatment with immunotherapy for advanced cancers such as melanoma, lung cancer, and bladder cancer [ 29 , 30 , 31 ]. Considering the recent spread of immune therapeutic agents, NLR is expected to be introduced in the treatment of uterine sarcoma in the near future [ 32 ]. Therefore, NLR could potentially be a more attractive and ideal marker that might provide valuable additional prognostic information.…”

Nivolumab plus ipilimumab versus nivolumab in individuals with treatment-naive programmed death-ligand 1 positive metastatic soft tissue sarcomas: a multicentre retrospective study

“…Antibodies against PD-1 or PD-L1 have a positive effect in blocking tumour immune evasion and inducing tumour regression in STS [ 7 , 24 ]. Previous reports [ 7 , 11 , 25 , 26 ] of PD-L1 expression have shown that STS is potentially responsive to PD-1/PD-L1 blockade intervention in STS patients with PD-L1 positivity. The survival benefit of NIV monotherapy is inconsistent with presently existing chemotherapy-based untargeted therapies [ 7 , 11 ].…”