Abstract: SA-PO176
Combination of Immune Checkpoint Inhibitor and Antiangiogenic Therapy for the First-Line Treatment of Advanced Renal Cell Carcinoma: A Combined Analysis of Three Phase 3 Randomized Controlled Trials
Session Information
- Onco-Nephrology: Clinical
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Onco-Nephrology
- 1500 Onco-Nephrology
Authors
- Sultan, Anita, Texas Tech University Health Sciences Center, Lubbock, Texas, United States
- Ahmed, Vaqar, Dallas Nephrology Associates, Dallas, Texas, United States
- Swarup, Sriman, Texas Tech University Health Sciences Center, Lubbock, Texas, United States
- Yendala, Rachana, Texas Tech University Health Sciences Center, Lubbock, Texas, United States
- Hninn, Wut yi, UTHealth, Houston, Texas, United States
- Lin, Maung htain K., Charles Wilson VA outpatient clinic, Houston, Texas, United States
- Htut, Thura Win, Aberdeen Royal Infirmary, Colchester, Essex, United Kingdom
- Waguespack, Dia Rose, McGovern Medical School - UTHealth - Houston, Houston, Texas, United States
- Thein, Kyaw Z., The University of Texas MD Anderson Cancer Center, Lubbock, Texas, United States
Background
Management of advanced renal cell carcinoma (RCC) is an area in dire need of therapeutic innovation. Sunitinib, a tyrosine kinase inhibitor targeting vascular endothelial growth factor (VEGF), has been the standard first-line treatment of advanced RCC for the past decade. Recently, combination of immune checkpoint inhibitor (ICI) and antiangiogenic agent has shown survival benefits. The purpose of our study is to stratify the efficacy of combination of ICI and antiangiogenic therapy for the first-line treatment of advanced RCC, according to international metastatic RCC database consortium (IMDC) risk groups and PD-L1 status.
Methods
PUBMED, MEDLINE, EMBASE databases and meeting abstracts from inception through May 2019 were queried. RCTs utilizing upfront combination of ICI and antiangiogenic therapy in patients with advanced RCC were incorporated. A generic inverse variance method was used to calculate the estimated pooled hazard ratio (HR) for progression-free survival (PFS) with 95% confidence interval (CI). Heterogeneity was assessed with Cochran’s Q -statistic.
Results
A total of 2662 patients from 3 phase III RCTs were included. The study arm used 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 0%, suggesting homogeneity among RCTs. The PFS benefit was observed in all IMDC risk groups, including favorable group (HR, 0.70; 95% CI: 0.52- 0.96; P = 0.02), intermediate group (HR, 0.71; 95% CI: 0.60- 0.84; P < 0.0001) and poor group (HR, 0.58; 95% CI: 0.42- 0.80; P = 0.0009). The PFS benefit was only noted in PD-L1 positive (≥1%) cohort with HR of 0.66 (95% CI: 0.57- 0.77; P < 0.0001).
Conclusion
Our study showed that combination of immune checkpoint inhibitor and antiangiogenic therapy significantly improved PFS compared to standard sunitinib in patients with advanced RCC, regardless of IMDC risk categories. However, PFS benefit was only noted in PD-L1 positive cohort and further strategies are warranted in PD-L1 negative subset.