Nomogram to Assess the Survival Benefit of New Salvage Agents for Metastatic Urothelial Carcinoma in the Era of Immunotherapy

Guru Sonpavde, Gregory Russell Pond, Jonathan E Rosenberg, Toni K Choueiri, Joaquim Bellmunt, Ashley Marie Regazzi, Stephanie A Mullane, Andrea Necchi, Daniele Raggi, Jae-Lyun Lee, Soonil Lee, Joe Simpson, Christina Louise Derleth, Shih-Wen Lin, Dean F Bajorin

Research output: Contribution to journalArticle

Abstract

INTRODUCTION: Optimal end points in phase 2 trials evaluating salvage therapy for metastatic urothelial carcinoma are necessary to identify promising drugs, particularly immunotherapeutics, where response and progression-free survival may be unreliable. We developed a nomogram using data from phase 2 trials of historical agents to estimate the 12-month overall survival (OS) for patients to which observed survival of nonrandomized data sets receiving immunotherapies could be compared.

PATIENTS AND METHODS: Survival and data for major prognostic factors were obtained from phase 2 trials: hemoglobin, performance status, liver metastasis, treatment-free interval, and albumin. A nomogram was developed to estimate 12-month OS. Patients were randomly allotted to discovery:validation data sets in a 2:1 ratio. Calibration plots were constructed in the validation data set and data bootstrapped to assess performance. The nomogram was tested on external nonrandomized cohorts of patients receiving pemetrexed and atezolizumab.

RESULTS: Data were available from 340 patients receiving sunitinib, everolimus, docetaxel + vandetanib, docetaxel + placebo, pazopanib, paclitaxel, or docetaxel. Calibration and prognostic ability were acceptable (c index = 0.634; 95% confidence interval [CI], 0.596-0.652). Observed 12-month survival for patients receiving pemetrexed (n = 127, 23.5%; 95% CI, 16.2-31.7) was similar to nomogram-predicted survival (19%; 95% CI, 16.5-21.5; P > .05), while observed results with atezolizumab (n = 403, 39.0%; 95% CI, 34.1-43.9) exceeded predicted results (24.6%; 95% CI, 23.4-25.8; P < .001).

CONCLUSION: This nomogram may be a useful tool to interpret results of nonrandomized phase 2 trials of salvage therapy for metastatic urothelial carcinoma by assessing the OS contributions of drug intervention independent of prognostic variables.

Original languageEnglish
Pages (from-to)e961-e967
JournalClinical Genitourinary Cancer
Volume16
Issue number4
DOIs
Publication statusPublished - Aug 2018

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Sonpavde, G., Pond, G. R., Rosenberg, J. E., Choueiri, T. K., Bellmunt, J., Regazzi, A. M., Mullane, S. A., Necchi, A., Raggi, D., Lee, J-L., Lee, S., Simpson, J., Derleth, C. L., Lin, S-W., & Bajorin, D. F. (2018). Nomogram to Assess the Survival Benefit of New Salvage Agents for Metastatic Urothelial Carcinoma in the Era of Immunotherapy. Clinical Genitourinary Cancer, 16(4), e961-e967. https://doi.org/10.1016/j.clgc.2018.03.016