Abstract 997P
Background
ICIs exhibited moderate anti-tumor activity in HCC. The failures of phase III trials evaluating the benefits from nivolumab or pembrolizumab vs. sorafenib suggested the necessity to investigate predictive biomarkers. The PD-L1 expression in tumor cells showed varied trends of association with ICI response in multiple trials. Here, this meta-analysis aims to evaluate the effect size of PD-L1 expression in predicting response to ICI therapy.
Methods
A systematic search was conducted in PubMed, Embase and Cochrane Library for the trials of ICI in HCC with PD-L1 assessment. Random-effects model were used to pool estimates of risk ratio (RR) and 95% confidence interval (95%CI) of objective response. Subgroup analysis were implemented to investigate the source of heterogeneity.
Results
In total, 9 eligible trials of 894 patients with data of PD-L1 expression and response were included. Of these, PD-L1 positivity was observed in 178 patients (19.9%). Pooled estimate of all trials revealed the positive association between PD-L1 positivity and objective response to ICI (RR=1.70, 95%CI 1.17-2.47, P=0.006), and the heterogeneity level was low (Tau2=0.00, I2=0.00%) and non-significant (P=0.76). This effect was minimal in trials of anti-PD-1 plus anti-CTLA4 combination therapy (RR=1.21, 95%CI 0.53-2.74, P=0.65) but remarkable in trials of anti-PD-1 monotherapy (RR=1.86, 95%CI 1.22-2.83, P=0.004). Table: 997P
| Trial | Regimen | Phase | PD-L1 antibody | PD-L1-positive | PD-L1-negative | ||||
| PR/CR | All | ORR | PR/CR | All | ORR | ||||
| NCT02989922 | Camrelizumab | 2 | SP142 | 4 | 11 | 36.4% | 2 | 19 | 10.5% |
| CheckMate 040 | Nivolumab | 1b | 28-8 | 3 | 11 | 27.3% | 4 | 33 | 12.1% |
| CheckMate 040 | Nivolumab | 2 | 28-8 | 9 | 34 | 26.5% | 26 | 140 | 18.6% |
| CheckMate 040 (Asian cohort) | Nivolumab | 2 | 28-8 | 2 | 16 | 12.5% | 15 | 67 | 22.4% |
| CheckMate 040 | NIVO1+IPI3 (q3w) | 1/2 | 28-8 | 3 | 10 | 30.0% | 12 | 39 | 30.8% |
| CheckMate 040 | NIVO3+IPI1 (q3w) | 1/2 | 28-8 | 3 | 10 | 30.0% | 12 | 38 | 31.6% |
| CheckMate 040 | NIVO3 (q2w)+IPI1 (q6w) | 1/2 | 28-8 | 4 | 8 | 50.0% | 11 | 40 | 27.5% |
| CheckMate 459 | Nivolumab | 3 | NA | 20 | 71 | 28.2% | 36 | 295 | 12.2% |
| KEYNOTE-224 | Pembrolizumab | 2 | 22C3 | 3 | 7 | 42.9% | 10 | 45 | 22.2% |
Conclusions
PD-L1 protein expression was associated with better response to ICI treatment, especially anti-PD-1 monotherapy. Minimal association between PD-L1 positivity and response to combination therapy might be account of the boost anti-tumor immunity by the addition of anti-CTLA-4, which warrants further investigations.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
Y. Xu, F. Gong: Full/Part-time employment: 3D Medicines Inc. All other authors have declared no conflicts of interest.