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Tumor Discovery Complete response to enfortumab vedotin in mBC

benefit. As an antibody-drug conjugate targeting nectin-4, following radical cystectomy. Although the indications
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it offers high tumor selectivity and, as observed in our and sequencing of PD-1/PD-L1 inhibitors can be complex,
case, can induce a rapid therapeutic response, making it an immunotherapy remains a critical component of treatment
effective targeted approach in heavily pretreated patients. for nearly all patients with mUC at some stage of their
To the best of our knowledge, our case represents one disease course. In line with the CheckMate 274 trial, our
of the most rapid complete responses to EV reported in patient had also received adjuvant nivolumab following
the literature for mUC. This case may serve as a valuable radical cystectomy.
reference, particularly in symptomatic patients or those Following the favorable responses observed with PD-1/
requiring a prompt therapeutic response.
PD-L1 inhibitors and EV, the EV-302/KEYNOTE-A39 trial
EV was first evaluated in the single-arm phase 2 trial was conducted to evaluate the efficacy of the combination
EV-201, where it demonstrated promising outcomes in of EV and pembrolizumab as a first-line therapy in
mUC patients previously treated with platinum-based patients with mUC. Compared to standard treatments, the
chemotherapy and immune checkpoint inhibitors. The combination demonstrated significant improvements in
study reported a median PFS of 5.8 months and a median both PFS and OS, positioning this regimen as a potentially
OS of 11.7 months. Subsequently, the phase 3 EV-301 trial new standard of care. 14
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compared EV with standard chemotherapy options in a Although our case demonstrates a favorable response
similar patient population. EV achieved a median OS of to EV, serving as a positive example for both clinicians
12.88 months versus 8.97 months with chemotherapy and a and patients, this observation is limited to one patient.
median PFS of 5.55 months versus 3.71 months, respectively. Questions remain regarding which subgroups of patients
In addition, the complete response rate in the EV arm was
4.9%, with a disease control rate of 71.9%. In our case, the are more likely to benefit from EV therapy. In particular,
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further research is needed to elucidate the relationship
patient had previously received platinum-based neoadjuvant between Nectin-4 expression levels and treatment response
chemotherapy and experienced disease progression under and identify novel predictive biomarkers that will refine
maintenance of nivolumab. Notably, a complete response
was achieved following treatment with EV. patient selection and improve prognostic assessment in
the future.
The median time to response for EV was reported as
1.8 months in the EV-201 trial and 1.41 months in the 4. Conclusion
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EV-301 trial. These findings suggest that EV provides a Although various treatment modalities, such as
rapid and effective tumor response in patients with mUC. chemotherapy, immunotherapy, and targeted agents,
However, neither study specified the exact time at which have expanded in the management of mUC, the overall
a complete response was achieved among responders. prognosis remains poor. EV has emerged as a valuable
6,7
In our case, a complete response was observed after two treatment alternative in this aggressive disease, where
cycles (approximately 2 months) of treatment. survival expectations are generally poor. However,
Immunotherapeutic agents have gained a significant questions remain regarding patient selection and the
role in the treatment algorithm of mUC by markedly potential correlation between treatment response and
improving OS, particularly through the use of PD-1 nectin-4 expression levels. Addressing these uncertainties
and PD-L1 inhibitors. For cisplatin-ineligible patients will require future studies involving larger patient cohorts
with mUC, first-line immunotherapy options include and comprehensive subgroup analyses.
atezolizumab, as demonstrated in the IMvigor210 trial,
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and pembrolizumab, as shown in the KEYNOTE-052 trial. Acknowledgments
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Pembrolizumab has shown an OS benefit in patients with None.
disease progression after platinum-based chemotherapy,
as demonstrated in the KEYNOTE-045 trial. Similarly, Funding
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nivolumab demonstrated efficacy as a second-line None.
treatment in the CheckMate 275 trial. In addition,
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avelumab provided a survival advantage as a maintenance Conflict of interest
therapy in patients who responded to platinum-based
chemotherapy, according to the findings of the JAVELIN The authors declare they have no competing interests.
Bladder 100 trial. The CheckMate 274 trial demonstrated Author contributions
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that adjuvant treatment with nivolumab significantly
prolonged disease-free survival in high-risk patients Conceptualization: Ali Kaan Güren

Volume 4 Issue 3 (2025) 94 doi: 10.36922/TD025150026