Abstract
Immune checkpoint inhibitors (ICIs) have become one of the mainstays of systemic therapy for advanced urothelial carcinoma (aUC). Increasingly ICIs are also being utilized earlier in the course of UC treatment. Limited data are available regarding ICI treatment efficacy in aUC patients who have progressed on prior ICI regimens. This case series aims to address this knowledge gap. We identified all aUC patients treated with ICI or combination following prior progression on another ICI regimen at two academic institutions. Patient demographic, clinicopathologic and treatment data were retrospectively collected from chart review at each site. Best response to ICI treatment was defined by investigator at each site. Among 7 patients with aUC who received ICI treatment following prior progression on a different ICI regimen, radiographic response to the second ICI regimen was observed in only 1 patient (14%) treated with combination of pembrolizumab/enfortumab vedotin. Efficacy of ICI treatment in patients who previously progressed on another ICI regimen appears limited. These observations should be validated in larger cohorts, as it is anticipated that this clinical scenario will become more common in the future.
Highlights
Immune checkpoint inhibitors (ICIs) have become one of the mainstays of systemic therapy for advanced urothelial carcinoma
Based on these recent trends, increasing numbers of advanced urothelial carcinoma (aUC) patients will likely be recommended to receive ICI or ICI combinations following prior treatment with similar regimens. The data for this approach in aUC is currently very limited, other studies have reported outcomes of sequential immunotherapy treatment in RCC or in phase I trials across solid malignancies.[18,19]. In this case report we present a multi-institutional experience of patients with aUC treated with more than one ICI regimen, and discuss the efficacy of this approach (Table 2, Figure 1)
This case series represents an important initial hypothesisgenerating effort that future studies can build on. This case series is an initial report describing ICI treatment following prior progression on a different ICI regimen in patients with aUC. The efficacy of this approach appears to be limited, with no patients responding to a pure ICI switch, and only 1 patient responding to a second line ICI/enfortumab vedotin (EV) combination regimen after previously having disease progression on ICI monotherapy
Summary
In recent years immune checkpoint inhibitors (ICI) have become the standard of care for patients with locally advanced or metastatic urothelial carcinoma (UC), as from 2016 to 2017 five different ICIs received FDA approval in the platinum-refractory setting: atezolizumab, pembrolizumab, nivolumab, avelumab and durvalumab.[1,2,3,4] Only pembrolizumab was supported by data from a phase III randomized trial showing an overall survival (OS) advantage over chemotherapy.[5]. Patient progressed on initial switch maintenance treatment with avelumab, but subsequently had good response to combination of pembrolizumab and enfortumab vedotin, with marked improvement in liver lesions Based on these recent trends, increasing numbers of aUC patients will likely be recommended to receive ICI or ICI combinations following prior treatment with similar regimens. Case 1 A 75 year old man initially diagnosed with muscle-invasive bladder cancer (MIBC) in early 2019 was enrolled in a clinical trial of neoadjuvant atezolizumab since he was cisplatin-ineligible He completed three cycles of atezolizumab from March 2019 to May 2019 followed by a radical cystectomy in May 2019. Surveillance scans in July 2019 revealed a new lung lesion which was biopsy-confirmed as aUC
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