ABSTRACT
Introduction
Immune checkpoint inhibitors (ICI) are part of the current standard of care for metastatic
clear-cell renal cell carcinoma (m-ccRCC). ICI can elicit diverse tumor response,
including atypical responses such as pseudoprogression (psPD), mixed responses (MR)
and late responses. We aimed to analyze the occurrence and prognostic impact of atypical
responses in m-ccRCC patients treated with nivolumab.
Materials and methods
A retrospective analysis of m-ccRCC patients treated with nivolumab in first or subsequent
therapy line between November 2012 and July 2022 was performed. All radiographic evaluations
of eligible patients were analyzed using the iRECIST consensus guideline.
Results
We assessed 247 baseline target lesions in 94 eligible patients. MR occurred in 11
(11.7%) patients: in 7 at first CT evaluation (CT1) and in 4 at second CT evaluation
(CT2). In 8 patients (73%), MR evolved to confirmed PD. In 3 patients (27%), MR evolved
towards a partial response (PR) and was thus a psPD. psPD occurred in 8 (8.5%) patients:
with psPD features at CT1 in 3 patients, with psPD features at CT2 in 2 patients,
and with MR features at CT1 in 3 patients. psPD patients had similar progression-free
survival and overall survival compared to patients displaying PR as best response
without a phase of psPD. 76 patients were treated beyond immune unconfirmed progressive
disease (iUPD) at any moment: 12 (16%) of them evolved towards PR or stable disease
(SD). Treatment beyond immune confirmed PD (iCPD) in 20 patients did not lead to PR
or SD.
Conclusions
Atypical responses such as psPD and MR occurred in 8.5% and 11.7% of m-ccRCC patients
treated with nivolumab at CT1 and CT2. Patients with psPD had favorable outcomes,
while MR most often evolved to progression. Treatment with nivolumab beyond iCPD did
not lead to tumor stabilization or regression.
MICROABSTRACT
Outcome of renal cell carcinoma has significantly improved with immune checkpoint
inhibitors. However, patients show atypical response such as mixed response and pseudoprogression.
We retrospectively analyzed 94 renal cell carcinoma patients and found 8.5% of pseudo-progressors
with similar outcome to responders. Our study adds to the limited evidence in this
area, helping clinicians treat their patients with immune checkpoint inhibitors.
Keywords
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Article info
Publication history
Accepted:
March 5,
2023
Received in revised form:
March 4,
2023
Received:
January 30,
2023
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2023 Elsevier Inc. All rights reserved.
