Skin Toxic Effects and Survival With Enfortumab Vedotin-Pembrolizumab in Advanced Urothelial Carcinoma.

@article{thomas2026skin,
  title = {{Skin Toxic Effects and Survival With Enfortumab Vedotin-Pembrolizumab in Advanced Urothelial Carcinoma.}},
  author = {Zachariah Thomas and Cindy Y Jiang and Patrick J Speck and Emanuele Crupi and Mohammad Jad Moussa and Adrienne Joseph and Carly Stender and Michael Glover and Andrew C Johns and Jianjun Gao and Monica Desai and Amishi Y Shah and Sangeeta Goswami and Arlene Siefker-Radtke and Anishia-Rawther Karedath and Sheeba P Varughese and Wenhong Ren and Comron Hassanzadeh and Kelly K Bree and Ashish M Kamat and Charles C Guo and Omar Pacha and Anisha Patel and Jonathan Curry and Alex D Sherry and Pavlos Msaouel and Matthew T Campbell and Omar Alhalabi},
  journal = {JAMA network open},
  year = {2026},
  month = oct,
  doi = {10.1001/jamanetworkopen.2026.39517},
  url = {https://europepmc.org/article/MED/42900474},
  note = {CC BY-NC-ND},
}

TY  - JOUR
TI  - Skin Toxic Effects and Survival With Enfortumab Vedotin-Pembrolizumab in Advanced Urothelial Carcinoma.
AU  - Zachariah Thomas
AU  - Cindy Y Jiang
AU  - Patrick J Speck
AU  - Emanuele Crupi
AU  - Mohammad Jad Moussa
AU  - Adrienne Joseph
AU  - Carly Stender
AU  - Michael Glover
AU  - Andrew C Johns
AU  - Jianjun Gao
AU  - Monica Desai
AU  - Amishi Y Shah
AU  - Sangeeta Goswami
AU  - Arlene Siefker-Radtke
AU  - Anishia-Rawther Karedath
AU  - Sheeba P Varughese
AU  - Wenhong Ren
AU  - Comron Hassanzadeh
AU  - Kelly K Bree
AU  - Ashish M Kamat
AU  - Charles C Guo
AU  - Omar Pacha
AU  - Anisha Patel
AU  - Jonathan Curry
AU  - Alex D Sherry
AU  - Pavlos Msaouel
AU  - Matthew T Campbell
AU  - Omar Alhalabi
PY  - 2026
DA  - 2026/10/01
JO  - JAMA network open
DO  - 10.1001/jamanetworkopen.2026.39517
UR  - https://europepmc.org/article/MED/42900474
AB  - Importance  Skin toxic effects are a common early adverse event of enfortumab vedotin plus pembrolizumab (EVP) therapy, but its association with clinical outcomes in patients receiving first-line therapy remains uncertain.Objective  To evaluate the association between treatment-emergent skin toxic effects and clinical outcomes among patients receiving first-line EVP.Design, setting, and participants  This retrospective cohort study was performed at the University of Texas MD Anderson Cancer Center among adults with locally advanced or metastatic urothelial carcinoma receiving first-line EVP therapy between March 3, 2022, and July 31, 2025. Skin toxic effects were used as a time-dependent exposure in Cox proportional hazards regression to account for immortal-time bias. Prespecified sequential adjustment models and 30-day landmark analyses were performed to assess the robustness of the findings.Exposure  Treatment-emergent skin toxic effects (rash or pruritus) were identified from medical records.Main outcomes and measures  Primary outcome was overall survival (OS). Secondary outcomes included progression-free survival and objective response rate (ORR). OS and PFS were measured from EVP therapy initiation to the respective event or last follow-up. ORR was evaluated among patients with a response assessment after the 30-day landmark, according to skin toxic effects status within the first 30 days.Results  Among 185 patients (median age, 73 [IQR, 67-79] years; 140 [75.7%] male), skin toxic effects occurred in 98 (53.0%) at a median of 14 (IQR, 7-28) days after EVP therapy initiation. Skin toxic effects of grade 3 or higher occurred in 10 patients (5.4%). Skin toxic effects resulted in EV dose reduction in 31 patients (16.8%), treatment interruption in 20 (10.8%), and treatment discontinuation in 9 (4.9%). At a median follow-up of 17.7 (IQR, 11.3-24.2) months, Simon-Makuch curves demonstrated longer OS and PFS among all patients and longer OS among patients with visceral metastases in the skin toxic effects stratum than in the no toxicity stratum. In adjusted time-dependent Cox proportional hazards regression, skin toxic effects were associated with longer OS (hazard ratio, 0.34 [95% CI, 0.20-0.57]). The association remained consistent across sequential adjustment models and prespecified 30-day landmark analyses. In the 30-day landmark analyses, associations with PFS and ORR remained directionally favorable but were attenuated after multivariable adjustment.Conclusions and relevance  In this cohort study of 185 patients with locally advanced or metastatic urothelial carcinoma receiving first-line EVP therapy, treatment-emergent skin toxic effects were associated with longer OS. These findings support further prospective validation of skin toxic effects as an early clinical marker of treatment benefit and investigation of the biological mechanisms underlying this association.
SN  - 2574-3805
ER  -