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
3252 - Genes involved in DNA replication, chromatin remodeling and cell cycle as potential biomarkers for therapy outcome to immune therapy in patients with metastatic cutaneous malignant melanoma
Presenter: Fernanda Costa Svedman
Session: Poster Display session 3
Resources:
Abstract
5545 - Phase Ib/II Study (SENSITIZE) assessing safety, pharmacokinetics (PK), pharmacodynamics (PD), and clinical outcome of domatinostat in combination with pembrolizumab in patients with advanced melanoma refractory/non-responding to prior checkpoint inhibitor therapy
Presenter: Jessica Hassel
Session: Poster Display session 3
Resources:
Abstract
5213 - Genomic landscape of primary malignant melanoma of esophagus
Presenter: Jie Dai
Session: Poster Display session 3
Resources:
Abstract
2716 - A phase III, randomised, double-blind study of adjuvant cemiplimab versus placebo post-surgery and radiation in patients with high-risk cutaneous squamous cell carcinoma (CSCC)
Presenter: Danny Rischin
Session: Poster Display session 3
Resources:
Abstract
3550 - ILLUMINATE 301: A randomized phase 3 study of tilsotolimod in combination with ipilimumab compared with ipilimumab alone in patients with advanced melanoma following progression on or after anti-PD-1 therapy
Presenter: Marcus Butler
Session: Poster Display session 3
Resources:
Abstract
1645 - PRIME002 - Early phase II study of Azacitidine and Carboplatin priming for Avelumab in patients with advanced melanoma who are resistant to immunotherapy
Presenter: Andre Van Der Westhuizen
Session: Poster Display session 3
Resources:
Abstract
4440 - Pembrolizumab (pembro) Plus Lenvatinib (len) for First-Line Treatment of patients (pts) With Advanced Melanoma: Phase 3 LEAP-003 Study
Presenter: Alexander Eggermont
Session: Poster Display session 3
Resources:
Abstract
3454 - Proof of concept study with the histone deacetylase inhibitor vorinostat in patients with resistant BRAFV600 mutated advanced melanoma
Presenter: Sanne Huijberts
Session: Poster Display session 3
Resources:
Abstract
1832 - A phase Ia/Ib clinical study to evaluate the safety, pharmacokinetics (PK) and preliminary anti-tumor activity of FCN-159 in patients with advanced melanoma harboring NRAS-aberrant (Ia) and NRAS-mutation (Ib).
Presenter: Lu Si
Session: Poster Display session 3
Resources:
Abstract
3996 - A Phase I Clinical Trial Investigating the Therapeutic Cancer Vaccine UV1 in Combination with Pembrolizumab as First-Line Treatment of Patients with Malignant Melanoma
Presenter: Sanjiv Agarwala
Session: Poster Display session 3
Resources:
Abstract