Sarcomatoid RCC patients benefit from immune checkpoint inhibitor therapy
medwireNews: Subgroup analysis of the IMmotion151 trial suggests improved survival with first-line atezolizumab plus bevacizumab versus sunitinib for locally advanced or metastatic renal cell carcinoma (RCC) patients with sarcomatoid differentiation.
Findings from the phase III open-label study of patients with inoperable, treatment-naïve disease have previously demonstrated significantly longer progression-free survival (PFS) with the combination regimen, as well as better quality of life.
The current analysis focuses on the subgroup of patients with sarcomatoid histology, of whom 68 received atezolizumab plus bevacizumab while 74 were given sunitinib.
Compared with patients in the intention-to-treat population, these sarcomatoid histology patients were more likely to have PD-L1-positive disease and MSKCC intermediate or poor risk disease, reported Brian Rini (Cleveland Clinic, Ohio, USA) and colleagues in a poster presented at the 2019 ASCO Annual Meeting in Chicago, Illinois, USA.
Among sarcomatoid histology patients overall, median PFS was significantly longer with the combination than monotherapy regimen, at 8.3 versus 5.3 months and a stratified hazard ratio (HR) of 0.52, and this outcome was even more favorable among sarcomatoid patients with PD-L1-positive tumors, at 8.6 versus 5.6 months and a significant stratified HR of 0.45.
There was also some evidence of improved overall survival in the sarcomatoid histology subgroup overall with atezolizumab plus bevacizumab versus sunitinib (21.7 vs 15.4 months, stratified HR=0.64) as well as among those who had PD-L1-positive disease (19.3 vs 15.0 months, stratified HR=0.61), although these did not reach statistical significance.
And there was a trend for symptoms to take longer to interfere with activities of daily living in patients with sarcomatoid histology given the combination regimen compared with sunitinib, at a median of 11.3 versus 4.9 months and a HR of 0.61, although again this difference did not reach significance.
The safety profile of atezolizumab plus bevacizumab in the sarcomatoid histology subgroup was “generally consistent” with earlier reports for the combination and the full study population, the researchers said.
As well as being more likely to have tumor PD-L1 expression, patients with sarcomatoid histology had a lower prevalence of the AngiogenesisHIGH gene expression signature and a higher prevalence of the T-effectorHIGH gene expression signature than those without sarcomatoid histology.
These findings “provide a biological correlate for the increased responsiveness to atezolizumab + bevacizumab in patients with metastatic RCC and a component of sarcomatoid histology,” the team concluded.
“On the basis of this subgroup analysis, immune checkpoint inhibitor therapy should be considered for patients with sarcomatoid differentiation.”
medwireNews is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group
This independent article was supported by an educational grant from Pfizer and Merck KGaA