METHODS: Publications were collected from PubMed, EMBASE, Cochrane Library, Web of Science, CNKI, Sino Med, VIP, and Wan Fang Databases. Relative risk (RR) was calculated with a 95 % confidence interval (CI). Heterogeneity was assessed. The Cochrane Collaboration's tool was used to assess the risk of bias.
RESULTS: 10 studies with 2702 patients showed that the combination therapy significantly reduced the incidence of HCC in patients with post-hepatitis B cirrhosis at 1, 3, and 5 years. However, the preventive effects of TCM were in compensated cirrhosis, but not the decompensated cirrhosis. Furthermore, TCM correlated with improved liver function and enhanced virological response.
CONCLUSION: Combination therapy with TCM demonstrated the certain potential in reducing the incidence of HCC in patients with hepatitis B cirrhosis. This is attrinuted to the improvement of liver function and enhancement of the viral response. However, the efficacy of TCM in the field still needs more high-quality RCTs to provide stronger evidence in the future.
METHODS: HRD status was determined using the ACTHRD assay, an enrichment-based targeted next-generation sequencing assay. PD-L1 expression was assessed by SP263 immunohistochemistry assay. PD-L1 expression positivity was defined by the PD-L1 expression on ≥ 1% of immune cells. Kaplan-Meier method was utilised to analyse progression-free survival (PFS).
RESULTS: This exploratory biomarker analysis included 225 patients and tested HRD status [N = 190; positive, N = 125 (65.8%)], PD-L1 expression [N = 196; positive, N = 56 (28.6%)], and BRCA1/2 mutation status (N = 219). The HRD-positive patients displayed greater median PFS than the HRD-negative patients [17.9 months (95% CI: 14.5-22.1) versus 9.2 months (95% CI: 7.5-13.8)]. PD-L1 was predominantly expressed on immune cells. Positive PD-L1 expression on immune cells was associated with shortened median PFS in the patients with germline BRCA1/2 mutations [14.5 months (95% CI: 7.4-18.2) versus 22.2 months (95% CI: 18.3-NA)]. Conversely, positive PD-L1 expression on immune cells was associated with prolonged median PFS in the patients with wild-type BRCA1/2 [20.9 months (95% CI: 13.9-NA) versus 8.3 months (95% CI: 6.7-13.8)].
CONCLUSIONS: HRD remained an effective biomarker for enhanced olaparib efficacy in the Asian patients with PSROC. Positive PD-L1 expression was associated with decreased olaparib efficacy in the patients with germline BRCA1/2 mutations but associated with improved olaparib efficacy in the patients with wild-type BRCA1/2.
TRIAL REGISTRATION: NCT03534453. Registered at May 23, 2018.