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

Clin Genitourin Cancer 2018 08 6;16(4):e961-e967. Epub 2018 Apr 6.

Memorial Sloan Kettering Cancer Center, New York, NY.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clgc.2018.03.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6697267PMC
August 2018

Publication Analysis

Top Keywords

phase trials
16
urothelial carcinoma
12
patients receiving
12
metastatic urothelial
12
salvage therapy
8
therapy metastatic
8
estimate 12-month
8
data sets
8
survival patients
8
12-month survival
8
receiving pemetrexed
8
survival
7
data
7
patients
5
95%
5
validation data
4
constructed validation
4
data set
4
plots constructed
4
calibration plots
4

Similar Publications