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

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.

• Authors: 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
• Journal: Clinical genitourinary cancer (Clin Genitourin Cancer) Vol. 16 Issue 4 Pg. e961-e967 (08 2018) ISSN: 1938-0682 [Electronic] United States
• PMID: 29706503 (Publication Type: Clinical Trial, Phase II, Journal Article)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Pemetrexed
• atezolizumab

Topics

• Aged
• Antibodies, Monoclonal (therapeutic use)
• Antibodies, Monoclonal, Humanized
• Carcinoma, Transitional Cell (drug therapy)
• Disease-Free Survival
• Female
• Humans
• Immunotherapy
• Male
• Middle Aged
• Nomograms
• Pemetrexed (therapeutic use)
• Prognosis
• Prospective Studies
• Random Allocation
• Salvage Therapy (methods)
• Treatment Outcome
• Urinary Bladder Neoplasms (drug therapy)