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Review
. 2020 Feb 10;12(2):408.
doi: 10.3390/cancers12020408.

Outcomes Associated with First-Line anti-PD-1/ PD-L1 agents vs. Sunitinib in Patients with Sarcomatoid Renal Cell Carcinoma: A Systematic Review and Meta-Analysis

Carlo Buonerba  1   2 , Pasquale Dolce  3 , Simona Iaccarino  4 , Luca Scafuri  4 , Antonio Verde  4 , Ferdinando Costabile  4 , Martina Pagliuca  4 , Rocco Morra  4 , Vittorio Riccio  4 , Dario Ribera  4 , Pietro De Placido  4 , Valeria Romeo  5 , Felice Crocetto  6 , Nicola Longo  6 , Ciro Imbimbo  6 , Sabino De Placido  4 , Giuseppe Di Lorenzo  7   8
Affiliations
Review

Outcomes Associated with First-Line anti-PD-1/ PD-L1 agents vs. Sunitinib in Patients with Sarcomatoid Renal Cell Carcinoma: A Systematic Review and Meta-Analysis

Carlo Buonerba et al. Cancers (Basel). .

Abstract

: Immunotherapy based on anti PD-1/PD-L1 inhibitors has proven to be more effective than sunitinib in the first-line setting of advanced renal cell carcinoma (RCC). RCC patients with sarcomatoid histology (sRCC) have a poor prognosis and limited therapeutic options. We performed a systematic review and a meta-analysis of randomized-controlled trials (RCTs) of first-line anti PD-1/PDL-1 agents vs. sunitinib, presenting efficacy data in the sub-group of sRCC patients. The systematic research was conducted on Google Scholar, Cochrane Library, PubMed and Embase and updated until 31th January, 2020. Abstracts from ESMO and ASCO (2010-2019) were also reviewed. Full texts and abstracts reporting about RCTs testing first-line anti-PD-1/ PD-L1 agents vs. sunitinib in RCC were included if sRCC sub-group analyses of either PFS (progression-free survival), OS (overall survival) or radiological response rate were available. Pooled data from 3814 RCC patients in the ITT (intention-to-treat) population and from 512 sRCC patients were included in the quantitative synthesis. In the sRCC sub-group vs. the ITT population, pooled estimates of the PFS-HRs were 0.57 (95%: 0.45-0.74) vs. 0.79 (95% CI: 0.70-0.89), respectively, with a statistically meaningful interaction favoring the sRCC sub-group (pooled ratio of the PFS-HRs = 0.64; 95% CI: 0.50-0.82; p < 0.001). Pooled estimates of the difference in CR-R (complete response-rate) achieved with anti-PD-1/PDL-1 agents vs. sunitinib were + 0.10 (95% CI: 0.04-0.16) vs. + 0.04 (95% CI: 0.00-0.07) in the sRCC vs. the non-sRCC sub groups, with a statistically meaningful difference of + 0.06 (95% CI: 0.02-0.10; p = 0.007) favoring the sRCC sub-group. Sarcomatoid histology may be associated with improved efficacy of anti PD-1/PDL-1 agents vs. sunitinib in terms of PFS and CR-R.

Keywords: PD-1; PD-L1; immune checkpoint inhibitors; renal cell carcinoma; sarcomatoid.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Flow-diagram of the systematic review.
Figure 2
Figure 2
Interactions between HR for progression or death and sarcomatoid histology. Funnel plots of PFS-HR for sarcomatoid sub-group and ITT population. Publication bias was evaluated by visual asymmetry and p-values are obtained by regression tests for funnel plot asymmetry. The y-axis reports standard error while the x-axis reports the effect sizes, that is, HR for PFS in sarcomatoid sub-group (left-hand size) and ITT (right-hand side).
Figure 3
Figure 3
Interactions between HR for progression or death and sarcomatoid histology. Ipi = Ipilimumab; Nivo = Nivolumab; Sun=Sunitinib; Ave=Avelumab; Axi = Axitinib; Atez = Atezolizumab; Beva = bevacizumab; Pembro = pembrolizumab; Sun = sunitinib.
Figure 4
Figure 4
Interactions between HR for death and sarcomatoid histology.
Figure 5
Figure 5
Interactions between complete response rate and sarcomatoid histology.
Figure 6
Figure 6
Interactions between partial response rate and sarcomatoid histology.
Figure 7
Figure 7
Leave-One-Out-Analyses. Pooled interaction estimates sorted by effect size.
See this image and copyright information in PMC

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