Abstract 1344
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.
Resources from the same session
5218 - Elevated driver mutational burden or number of perturbed pathways and poor response to abiraterone or enzalutamide in metastatic castration-resistant prostate cancer
Presenter: Bram De Laere
Session: Poster Display session 3
Resources:
Abstract
2452 - High proportion of multiple KRAS mutations in circulating tumor DNA and tumor tissue of pancreatic ductal adenocarcinoma
Presenter: Min Kyeong Kim
Session: Poster Display session 3
Resources:
Abstract
3328 - Biological difference of tumor mutational burden (TMB) and microsatellite instability (MSI) status in patients (pts) with somatic vs. germline BRCA1/2-mutated advanced gastrointestinal (GI) cancers using cell-free DNA (cfDNA) sequencing analysis in the GOZILA study
Presenter: Yasuyuki Kawamoto
Session: Poster Display session 3
Resources:
Abstract
3022 - Cell-Free DNA to Detect Focal Versus Non-Focal MET Amplification in Metastatic Colorectal Cancer Patients: Combined Analysis from Japan and the United States
Presenter: Mishima Saori
Session: Poster Display session 3
Resources:
Abstract
2833 - Presence of circulating tumor DNA in surgically resected renal cell carcinoma is associated with advanced disease and poor patient prognosis
Presenter: Andres Correa
Session: Poster Display session 3
Resources:
Abstract
1376 - Combined genomic and epigenomic assessment of cell-free circulating tumor DNA (cfDNA) for cancer diagnosis and recurrence-risk assessment in early-stage lung cancer
Presenter: Junghee Lee
Session: Poster Display session 3
Resources:
Abstract
4050 - DEMo: a prospective evaluation of a prognostic clinico-molecular composite score in NSCLC patients treated with immunotherapy.
Presenter: Arsela Prelaj
Session: Poster Display session 3
Resources:
Abstract
4727 - Bespoke circulating tumor DNA (ctDNA) analysis as a predictive biomarker in solid tumor patients (pts) treated with single agent pembrolizumab (P)
Presenter: Cindy Yang
Session: Poster Display session 3
Resources:
Abstract
3662 - Dynamic changes in whole-genome cell-free DNA (cfDNA) to identify disease progression prior to imaging in advanced solid tumors
Presenter: Andrew Davis
Session: Poster Display session 3
Resources:
Abstract
3817 - Evaluation of Microsatellite Instability Testing Through cell-free DNA sequencing
Presenter: Shile Zhang
Session: Poster Display session 3
Resources:
Abstract