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Association of prior local therapy and outcomes with PD(L)1 inhibitor in advanced urothelial cancer. BJU international Makrakis, D., Talukder, R., Diamantopoulos, L. N., Carril-Ajuria, L., Castellano, D., De Kouchkovsky, I., Koshkin, V. S., Park, J. J., Alva, A., Bilen, M. A., Stewart, T. F., McKay, R. R., Santos, V. S., Agarwal, N., Jain, J., Zakharia, Y., Morales-Barrera, R., Devitt, M. E., Grant, M., Lythgoe, M. P., Pinato, D. J., Nelson, A., Hoimes, C. J., Shreck, E., Gartrell, B. A., Sankin, A., Tripathi, A., Zakopoulou, R., Bamias, A., Murgic, J., Frobe, A., Rodriguez-Vida, A., Drakaki, A., Liu, S., Kumar, V., Di Lorenzo, G., Joshi, M., Isaacsson-Velho, P., Buznego, L. A., Duran, I., Moses, M., Barata, P., Sonpavde, G., Yu, E. Y., Wright, J. L., Grivas, P., Khaki, A. R. 2021

Abstract

OBJECTIVES: To compare clinical outcomes with anti-PD(L)1 immune checkpoint inhibitors (ICIs) in patients with advanced urothelial carcinoma (aUC) who have vs have not undergone radical surgery (RS) or radiation (RT) prior to developing metastatic disease.PATIENTS AND METHODS: We performed a retrospective cohort study collecting clinicopathological, treatment and outcomes data for patients with aUC receiving ICIs across 25 institutions. We compared outcomes (observed response rate [ORR], progression-free survival [PFS], overall survival [OS]) between patients with vs without prior RS, and by type of prior locoregional treatment (RS vs RT vs no locoregional treatment). Patients with de novo advanced disease were excluded. Analysis was stratified by treatment line (first [1st ] & second or greater [2nd+ ]). Logistic regression was used to compare ORR; Kaplan-Meier analysis and Cox regression for PFS and OS. Multivariable models were adjusted for known prognostic factors.RESULTS: We included 562 patients (1st line: 342 and 2nd+ : 220). There was no difference in outcomes based on prior locoregional treatment among those treated with 1st line ICI. In the 2nd+ line, prior RS was associated with higher ORR (adjusted odds ratio [aOR] 2.61 [95% CI 1.19-5.74]), longer OS (adjusted hazard ratio [aHR] 0.61 [95% CI 0.42-0.88]) and PFS (aHR 0.63 [95% CI 0.45-0.89]) vs no prior RS. This association remained significant when the type of prior locoregional treatment (RS and RT) was modeled separately.CONCLUSION: Prior RS prior to developing advanced disease was associated with better outcomes in patients with aUC treated with ICI in the 2nd+ , but not in the 1st line setting. While further validation is needed, our findings can have implications on prognostic estimates in clinical discussions and benchmarking for clinical trials. Limitations include retrospective nature, lack of randomization, possible selection and confounding biases.

View details for DOI 10.1111/bju.15603

View details for PubMedID 34597472