Survey-based study of treatment sequencing after first-line (1L) enfortumab vedotin/pembrolizumab (EVP) in the evolving landscape of locally advanced/metastatic (la/m) urothelial cancer (UC).
Authors: Chablani Priyanka Vinod , Khaki Ali Raza , Tawagi Karine , Grivas Petros , Hoffman-Censits Jeannie , Galsky Matthew D. , Gupta Shilpa , Koshkin Vadim S , Plimack Elizabeth R. , Rosenberg Jonathan E. , O'Donnell Peter H. 
Published: February 2025

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Background:
EVP is a preferred 1st-line option for patients (pts) with la/m UC. We sought to understand how genitourinary (GU) medical oncologists in the US treat pts who progress on 1L EVP, and their comfort level with immune checkpoint inhibitor (ICI) rechallenge after prior ICI exposure.
Methods:
We convened a bladder cancer working group comprised of 11 expert la/m UC GU oncologists. This group created an 11-question survey addressing key questions regarding treatment sequencing, including treatment after 1L EVP. The survey was e-mailed to 227 US GU oncologists from May - Aug 2024. GU oncologists in the Bladder Cancer Advocacy Network and those with a known GU-focus in academic and community practices were selected. Here, we present results regarding 2L treatment after 1L EVP, using descriptive statistics.
Results:
We received 78/227 responses (34%); 72% report seeing > 25 pts with la/m UC/yr, 21% see 11-25 pts/yr. 71 oncologists completed the 2L treatment question. After progression on EVP, 77% (55/71) were somewhat/very
likely
to give platinum-based chemotherapy (PBC), 80% (57/71) would not include nivolumab with gemcitabine + cisplatin in the 2L, and 62% (44/71) were somewhat/very
unlikely
to give switch maintenance ICI after 2L PBC (Table). For other 2L options, 87% (62/71) were somewhat/very
likely
to give erdafitinib in pts with
FGFR3
alterations (alt), and 56% (40/71) were somewhat/very
likely
to give sacituzumab govitecan (SG). SG use before and after TROPiCS-04 trial press release on 5/30/24 shifted from 63% (24/38) to 48% (16/33) somewhat/very
likely
to use SG (and 21% [8/38] to 39% [13/33] somewhat/very
unlikely
to use). Regarding clinical trials after 1L EVP, 80% (57/71) were somewhat/very
likely
to recommend a
non
-ICI containing trial.
Conclusions:
After progression on EVP, most GU oncologists favor PBC without combination ICI, PBC without ICI switch maintenance, or erdafitinib (in FGFR3-alt) as 2L therapies. For clinical trials 2L, more oncologists favor a
non
-ICI containing regimen. Additional data, including the impact of residual toxicity from 1L EVP on 2L treatment selection, and treatment of pts with HER-2 IHC3+ tumors, are needed to better understand treatment sequencing for pts with la/m UC. At the time of survey build, trastuzumab deruxtecan had recently received pan-tumor approval. Limitations include selection bias and lack of clinical outcomes.

2L Treatment after EVP

Somewhat or very
likely
to use, % (n)

Somewhat or very
unlikely
to use, % (n)

Gemcitabine + Cisplatin + Nivolumab
11 (8)
80 (57)

PBC with switch maintenance ICI
31 (22)
62 (44)

PBC without switch maintenance ICI
77 (55)
13 (9)

Erdafitinib for
FGFR3
-alt

87 (62)
7 (5)

SG
56 (40)
30 (21)

ICI-combo trial
54 (38)
35 (25)

Non-ICI trial
80 (57)
8 (6)

Continue EVP for progression in 1-2 sites after using local therapy (e.g. radiation)
83 (59)
8 (6)