Abstract
Combination treatments with immuno-oncology (IO) agents and IO agents plus a vascular
endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) have been
approved for first-line treatment of patients with metastatic renal cell carcinoma
(mRCC). No direct comparisons have been performed among these treatment options. We
performed a systematic review and network meta-analysis to compare and rank the available
regimens for first-line treatment in terms of survival benefit and efficacy. In accordance
with the Preferred Reporting Items for Systematic Review statement, a systematic search
of reported studies was performed in MEDLINE, the Cochrane Central Register of Controlled
Trials, and EMBASE up to May 31, 2019. Network meta-analysis models were adjusted
using the Bayesian method. Four randomized clinical trials, with a total of 3758 patients,
met the inclusion criteria. Considering systemic therapy, 1880 patients had received
sunitinib and 550, 432, 442, and 454 patients had received ipilimumab plus nivolumab
(ipi + nivo), pembrolizumab plus axitinib (pembro + axi), avelumab plus axitinib (avelu +
axi), and atezolizumab plus bevacizumab (atezo + bev). No difference was found in
overall survival between ipi + nivo and pembro + axi for the intention to treat population
(hazard ratio [HR], 1.34; 95% credible interval [CrI], 0.92-1.97). No difference was
found in progression-free survival among the treatments. The overall response rate
(ORR) was superior with pembro + axi and avelu + axi compared with the ORR with the
other treatments (atezo + bev vs. pembro + axi: HR, 0.66; 95% CrI, 0.52-0.84; ipi +
nivo vs. pembro + axi: HR, 0.73; 95% CrI, 0.59-0.90; atezo + bev vs. avelu + axi:
HR, 0.55; 95% CrI, 0.43-0.71; avelu + axi vs. ipi + nivo: HR, 1.66; 95% CrI, 1.31-2.12),
with no differences across them (HR, 1.21; 95% CrI, 0.95-1.53). In the present indirect
comparison, for an intention to treat population, we found no survival differences
between pembro + axi and ipi + nivo. All treatments showed better progression-free
survival compared with sunitinib that was similar among them. The combination of an
IO agent (pembrolizumab or avelumab) and axitinib seemed to be the most effective
therapy for the ORR.
Keywords
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Article info
Publication history
Published online: March 03, 2020
Accepted:
February 23,
2020
Received in revised form:
February 23,
2020
Received:
January 20,
2020
Identification
Copyright
© 2020 Elsevier Inc. All rights reserved.
