Nivolumab demonstrates benefit over nomogram-predicted 12-month survival as salvage therapy for metastatic urothelial carcinoma.
Conferences
Overview
Research
Identity
Additional Document Info
View All
Overview
abstract
451 Background: Intermediate endpoints of benefit in metastatic urothelial carcinoma (mUC) nonrandomized trials are necessary to identify promising drugs, particularly for checkpoint inhibitors, where response and progression-free survival remain suboptimal. We previously reported a nomogram (Pond GR et al, 2017 GU Cancers Symposium) using 5 prognostic factors (hemoglobin < 10 g/dL, Eastern Cooperative Oncology Group performance status ≥1, presence of liver metastasis, time from last treatment ≤3 months, and albumin < lower limit of normal) from phase 2 trials of historical agents (eg, taxanes) to estimate 12-month overall survival (OS), against which observed survival could be compared. Nivolumab was granted approval as salvage therapy for patients with mUC, based on the CheckMate (CM) 275 trial; it is thus of interest to compare the nivolumab observed survival versus nomogram-predicted survival results. Methods: Data were obtained from CM 275, including survival and all 5 prognostic factors. Nomogram points were calculated and the expected 12-month OS was estimated. Bootstrap analyses based on 2000 replications were used to estimate 95% confidence intervals (CIs) for the median expected, observed, and difference between the expected and observed 12-month OS values. All tests were 2-sided, with statistical significance defined as P≤0.05. Results: Data were available from 270 patients from CM 275. Fifteen patients did not have albumin recorded and were excluded. Among the 255 evaluable patients, 46 (18.0%) patients had 0 adverse prognostic factors, 85 (33.3%) had 1, and 124 (48.6%) had 2 or more. The observed nivolumab 12-month OS from CM 275 (43.3% [95% CI, 37.0%-50.5%]) was 19.8% higher (95% CI, 13.6%-26.4%) when compared with the nomogram-predicted 12-month OS (23.5%; [95% CI, 22.5%-25.5%]) if patients received historical chemotherapy. Across all 2000 bootstrap samples, the observed nivolumab 12-month OS exceeded the nomogram-predicted 12-month OS. Conclusions: Nivolumab was associated with a significantly improved 12-month OS compared with historical chemotherapy based on the value predicted by the validated nomogram incorporating baseline prognostic factors. Clinical trial information: NCT02387996.
