1344 - Combination therapy with checkpoint inhibitors for first-line treatment of advanced renal cell carcinoma: A systematic review and meta-analysis of randomized controlled trials

Background

Management of advanced renal cell carcinoma (RCC) is an area in dire need of therapeutic innovation. In recent years, combining immunotherapy with chemotherapy has shown synergistic anticancer activities and multiple randomized clinical trials (RCT) have combined checkpoint inhibitors with chemotherapy as first-line treatment of advanced RCC. We undertook a combined analysis of phase III trials to evaluate the efficacy of first-line checkpoint inhibitors combination therapy in patients with advanced RCC.

Methods

We systematically conducted a comprehensive literature search using PUBMED, MEDLINE, EMBASE databases and meeting abstracts from inception through March 2019. RCTs utilizing first-line checkpoint inhibitors combination therapy in patients with advanced RCC were incorporated. A generic inverse variance method was used to calculate the estimated pooled hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS) with 95% confidence interval (CI). Heterogeneity was assessed with Cochran’s Q -statistic. Random effects model was applied.

Results

Four phase III RCTs (CheckMate 214, IMmotion 151, Javelin Renal 101 and Keynote-426) including 3758 patients with advanced RCC were eligible. The study arm used nivolumab+ ipilimumab, pembrolizumab+ axitinib, avelumab+ axitinib or atezolizumab+ bevacizumab while control arm utilized sunitinib. The randomization ratio was 1:1 in all studies. The I² statistic for heterogeneity was 24%, suggesting some heterogeneity among RCTs. The pooled HR for PFS was statistically significant at 0.79 (95% CI: 0.67-0.94; P = 0.008) and the pooled HR for OS was 0.70 (95% CI: 0.58- 0.85; P = 0.0002). In PD-L1 positive/ combined positive score of ≥ 1% cohort, the pooled HR for PFS was noted at 0.62 (95% CI: 0.53- 0.73; P < 0.00001).

Conclusions

Our meta-analysis demonstrated that upfront checkpoint inhibitors combination regimen significantly improved progression-free survival and overall survival compared to standard sunitinib in patients with advanced renal cell carcinoma, favoring combination regimen.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Kyaw Zin Thein.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.