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.
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: Ali Raza Khaki; Ang Li; Leonidas N Diamantopoulos; Natalie J Miller; Lucia Carril-Ajuria; Daniel Castellano; Ivan De Kouchkovsky; Vadim Koshkin; Joseph Park; Ajjai Alva; Mehmet A Bilen; Tyler Stewart; Victor Santos; Neeraj Agarwal; Jayanshu Jain; Yousef Zakharia; Rafael Morales-Barrera; Michael Devitt; Ariel Nelson; Christopher J Hoimes; Evan Shreck; Benjamin A Gartrell; Alex Sankin; Abhishek Tripathi; Roubini Zakopoulou; Aristotelis Bamias; Alejo Rodriguez-Vida; Alexandra Drakaki; Sandy Liu; Vivek Kumar; Mark P Lythgoe; David J Pinato; Jure Murgic; Ana Fröbe; Monika Joshi; Pedro Isaacsson Velho; Noah Hahn; Lucia Alonso Buznego; Ignacio Duran; Marcus Moses; Pedro Barata; Matthew D Galsky; Guru Sonpavde; Evan Y Yu; Veena Shankaran; Gary H Lyman; Petros Grivas Journal: Eur Urol Oncol Date: 2021-01-07
Authors: Pau Sarrio-Sanz; Laura Martinez-Cayuelas; Vicente Francisco Gil-Guillen; José Antonio Quesada; Luis Gomez-Perez Journal: J Clin Med Date: 2022-02-10 Impact factor: 4.241
Authors: Ali Raza Khaki; Ang Li; Leonidas N Diamantopoulos; Mehmet A Bilen; Victor Santos; John Esther; Rafael Morales-Barrera; Michael Devitt; Ariel Nelson; Christopher J Hoimes; Evan Shreck; Hussein Assi; Benjamin A Gartrell; Alex Sankin; Alejo Rodriguez-Vida; Mark Lythgoe; David J Pinato; Alexandra Drakaki; Monika Joshi; Pedro Isaacsson Velho; Noah Hahn; Sandy Liu; Lucia Alonso Buznego; Ignacio Duran; Marcus Moses; Jayanshu Jain; Jure Murgic; Praneeth Baratam; Pedro Barata; Abhishek Tripathi; Yousef Zakharia; Matthew D Galsky; Guru Sonpavde; Evan Y Yu; Veena Shankaran; Gary H Lyman; Petros Grivas Journal: Cancer Date: 2019-12-12 Impact factor: 6.921