ABSTRACT
Introduction
Combination immune checkpoint inhibitors (ICI) and vascular endothelial growth factor
receptor tyrosine kinase inhibitors (VEGF-R-TKI), including pembrolizumab/axitinib,
are approved for first-line treatment of metastatic renal cell carcinoma (mRCC). Pembrolizumab/axitinib
is associated with superior progression free survival (PFS), objective response rate
(ORR), and overall survival over sunitinib. However, to date, the activity and safety
of pembrolizumab/axitinib in later lines of therapy has not been reported.
Materials and Methods
Clinical data of consecutive patients receiving pembrolizumab/axitinib in the second-line
or beyond for mRCC at Yale-New Haven Hospital were retrospectively collected. Best
objective response was assessed using RECIST 1.1 criteria. Kaplan-Meier function was
used to analyze survival.
Results
Thirty-eight patients were included. Median age was 64, 92.1% had clear cell mRCC,
18.4% had sarcomatoid dedifferentiation; 94.7% had prior ICI and 39.5% had prior VEGF-R-TKI.
Pembrolizumab/axitinib was administered as second-line therapy in 21 (55.5%) patients,
third-line in 5 (13.2%) and beyond in 12 (30.2%). Adverse events (AEs) occurred in
86.8% of patients. Grade 3-4 AEs attributed to pembrolizumab and axitinib were seen
in 18.4% and 6.4% of patients, respectively. No grade 5 AEs occurred. At a median
follow up of 17.1 months, median PFS was 9.7 months (95% CI, 4.1-15.3). Amongst 36
response evaluable patients, the ORR was 25.0% (all partial) and disease control rate
(including stable disease for at least 6 months) was 66.6%. The most frequent treatment
sequence was first-line nivolumab/ipilimumab followed by second-line pembrolizumab/axitinib
(n = 17, 44.7%); among this cohort, median PFS with pembrolizumab/axitinib was 11.1
(95% CI, 8.4-13.7) months, with an ORR of 31.4%.
Conclusion
Combination pembrolizumab/axitinib among previously treated mRCC patients has activity,
with AE rates comparable to those reported in the first line. Prospective studies
evaluating ICI-VEGF-R-TKI combinations beyond first-line are warranted to identify
the most beneficial treatment sequencing in mRCC.
Keywords
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Article info
Publication history
Published online: January 11, 2023
Accepted:
January 5,
2023
Received in revised form:
January 3,
2023
Received:
August 23,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2023 Elsevier Inc. All rights reserved.
