Recent studies have reported that serum microRNAs (miRNAs) are potentially useful cancer biomarkers. In patients with gastric cancer (GC), the efficacy of nivolumab (Nivo), a PD-1 inhibitor, was shown in a phase III study, but predictive biomarkers of Nivo for gastric cancer have not been found. We investigated whether serum miRNAs could be predictive markers of the efficacy of Nivo in GC.
The subjects of this study were 20 patients who were enrolled in the phase III study (ONO-4538-12) and received Nivo 3 mg/kg IV Q2W at our institution. Expressions of 2565 miRNAs in the serum samples before and during treatment were analyzed using “3D-Gene” Human miRNA Oligo Chip (Toray Industries, Inc.). We explored miRNAs that were significantly associated with the treatment response using receiver operating characteristic analysis and Cox regression analysis.
Median progression-free survival (PFS) was 2.3 month, and partial response was achieved in four of the 20 patients who received Nivo. Serum samples before (n = 20) and 4 weeks after (n = 17) the treatment of Nivo were available. Two different miRNAs, one before and the other after treatment, were identifiedwhich were related to response to Nivo. AUC of miR-A identified before treatment was 0.88, whereas that of miR-B after the first treatment was 0.85. The overall response rate (ORR) was 44% (4/9) in miR-A-high patients and 0% (0/11) in miR-A-low patients. The ORR was 50% (4/8) in miR-B-high patients and 0% (0/9) in miR-B-low patients. Median PFS was 14.3 m (95%CI: N/A-35.1) in miR-A-high patients and 1.6 m (95%CI: 0.9-2.3) in miR-A–low patients (HR = 0.19, log rank: p = 0.01), and those were 5.6 m (95%CI: N/A-35.1) and 1.6 m (95%CI: 0.9-2.3) in miR-B-high patients (HR = 0.21, log rank: p = 0.01), respectively.
The two miRNAs in GC pts may be a predictive marker for identifying pts who derived greater benefit from Nivo therapy.
Clinical trial identification
Legal entity responsible for the study
Has not received any funding.
S. Takizawa: Personal fees: Toray Industries, Inc., outside the submitted work. O. Takahiro: Grants: Kewpie Corporation, Takeda, BioMimetics Sympathies, Rohto Pharmaceutical Co., Ltd., Inter Stem, Japan Atherosclerosis Research Foundation, Ono Pharmaceutical Co., Ltd., Daiichi-Sankyo Company. All other authors have declared no conflicts of interest.