Nomogram to assess the survival benefit of new salvage agents for metastatic urothelial carcinoma in the era of immunotherapy Journal Article
| Authors: | 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. |
| Article Title: | Nomogram to assess the survival benefit of new salvage agents for metastatic urothelial carcinoma in the era of immunotherapy |
| Abstract: | Response and progression-free survival are unreliable in providing signals of benefit of new agents, especially immunotherapy, in nonrandomized phase 2 trials of salvage therapy for metastatic urothelial carcinoma. A nomogram that used baseline prognostic variables was developed to estimate the 12-month survival of patients receiving salvage chemotherapy to which observed survival of nonrandomized data sets could be compared to interpret results. 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. © 2018 Elsevier Inc. |
| Keywords: | salvage therapy; immunotherapy; atezolizumab; postplatinum |
| Journal Title: | Clinical Genitourinary Cancer |
| Volume: | 16 |
| Issue: | 4 |
| ISSN: | 1558-7673 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2018-08-01 |
| Start Page: | e961 |
| End Page: | e967 |
| Language: | English |
| DOI: | 10.1016/j.clgc.2018.03.016 |
| PROVIDER: | scopus |
| PUBMED: | 29706503 |
| PMCID: | PMC6697267 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 August 2018 -- Source: Scopus |
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