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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Nomograms
Immunotherapy
docetaxel
Carcinoma
Survival
Pemetrexed
Confidence Intervals
Salvage Therapy
Calibration
Paclitaxel
Pharmaceutical Preparations
Disease-Free Survival
Albumins
Hemoglobins
Placebos
Neoplasm Metastasis
Liver
Datasets

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Sonpavde, G., Pond, G. R., Rosenberg, J. E., Choueiri, T. K., Bellmunt, J., Regazzi, A. M., ... 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

Nomogram to Assess the Survival Benefit of New Salvage Agents for Metastatic Urothelial Carcinoma in the Era of Immunotherapy. / Sonpavde, Guru; Pond, Gregory Russell; Rosenberg, Jonathan E; Choueiri, Toni K; Bellmunt, Joaquim; Regazzi, Ashley Marie; Mullane, Stephanie A; Necchi, Andrea; Raggi, Daniele; Lee, Jae-Lyun; Lee, Soonil; Simpson, Joe; Derleth, Christina Louise; Lin, Shih-Wen; Bajorin, Dean F.

In: Clinical Genitourinary Cancer, Vol. 16, No. 4, 08.2018, p. e961-e967.

Research output: Contribution to journalArticle

Sonpavde, G, Pond, GR, Rosenberg, JE, Choueiri, TK, Bellmunt, J, Regazzi, AM, Mullane, SA, Necchi, A, Raggi, D, Lee, J-L, Lee, S, Simpson, J, Derleth, CL, Lin, S-W & Bajorin, DF 2018, 'Nomogram to Assess the Survival Benefit of New Salvage Agents for Metastatic Urothelial Carcinoma in the Era of Immunotherapy', Clinical Genitourinary Cancer, vol. 16, no. 4, pp. e961-e967. https://doi.org/10.1016/j.clgc.2018.03.016
Sonpavde, Guru ; Pond, Gregory Russell ; Rosenberg, Jonathan E ; Choueiri, Toni K ; Bellmunt, Joaquim ; Regazzi, Ashley Marie ; Mullane, Stephanie A ; Necchi, Andrea ; Raggi, Daniele ; Lee, Jae-Lyun ; Lee, Soonil ; Simpson, Joe ; Derleth, Christina Louise ; Lin, Shih-Wen ; Bajorin, Dean F. / Nomogram to Assess the Survival Benefit of New Salvage Agents for Metastatic Urothelial Carcinoma in the Era of Immunotherapy. In: Clinical Genitourinary Cancer. 2018 ; Vol. 16, No. 4. pp. e961-e967.
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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.",
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T1 - Nomogram to Assess the Survival Benefit of New Salvage Agents for Metastatic Urothelial Carcinoma in the Era of Immunotherapy

AU - Sonpavde, Guru

AU - Pond, Gregory Russell

AU - Rosenberg, Jonathan E

AU - Choueiri, Toni K

AU - Bellmunt, Joaquim

AU - Regazzi, Ashley Marie

AU - Mullane, Stephanie A

AU - Necchi, Andrea

AU - Raggi, Daniele

AU - Lee, Jae-Lyun

AU - Lee, Soonil

AU - Simpson, Joe

AU - Derleth, Christina Louise

AU - Lin, Shih-Wen

AU - Bajorin, Dean F

N1 - Copyright © 2018 Elsevier Inc. All rights reserved.

PY - 2018/8

Y1 - 2018/8

N2 - 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.

AB - 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.

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DO - 10.1016/j.clgc.2018.03.016

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JO - Clinical Genitourinary Cancer

JF - Clinical Genitourinary Cancer

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