Prognostic factors in patients with metastatic urothelial carcinoma who have treated with Atezolizumab

Background: We evaluated the prognostic efficacy of the Geriatric Nutritional Risk Index (GNRI) in second-line pembrolizumab (PEM) therapy for patients with metastatic urothelial carcinoma (mUC). Patients and Methods: From January 2018 to October 2019, 52 mUC patients, treated previously with platinum-based chemotherapy, underwent second-line PEM therapy. Peripheral blood parameters were measured at the start of treatment: serum neutrophil-to-lymphocyte ratio (NLR), serum albumin, serum C-reactive protein (CRP), and body height and weight. PEM was intravenously administered (200 mg every 3 weeks). The patients were organized into two groups based on their GNRI (<92 [low GNRI] and ≥92 [high GNRI]), and the data were retrospectively analyzed. Adverse events (AEs) were evaluated and imaging studies assessed for all patients. Analyses of survival and recurrence were performed using Kaplan-Meier curves. Potential prognostic factors affecting cancer-specific survival (CSS) were assessed by univariate and multivariate Cox regression analyses. Results: patients’ baseline characteristics, except for their BMI and objective response rate, did not significantly differ between the two groups. The median total number of cycles of PEM therapy was significantly higher for the high-GNRI group (n [range]: 6 [2–20] vs. 3 [1–6]). The median CSS with second-line PEM therapy was 3.6 months (95% confidence interval [CI]: 2.5–6.1) and 11.8 months (95% CI: 6.2–NA) in the low-GNRI and the high-GNRI group (p < 0.01), respectively. Significant differences in CSS between the low- and high-CRP or -NRL groups were not found. Multivariate Cox proportional-hazards regression analysis revealed that a poor Eastern Cooperative Oncology Group performance status, visceral metastasis, and a low GNRI were significant prognostic factors for short CSS (95% CI: 1.62–6.10, HR: 3.14; 95% CI: 1.13–8.11, HR: 3.03; 95% CI: 1.32–8.02, HR: 3.25, respectively). Of the AEs, fatigue showed a significantly higher incidence in the low-GNRI group. Conclusions: For mUC patients receiving second-line PEM therapy, the GNRI is a useful predictive biomarker for survival outcome.

Download Full-text

Outcome and prognostic factors in metastatic urothelial carcinoma patients receiving second-line chemotherapy: an analysis of real-world clinical practice data in Japan

Japanese Journal of Clinical Oncology ◽

10.1093/jjco/hyy094 ◽

2018 ◽

Vol 48 (8) ◽

pp. 771-776 ◽

Cited By ~ 7

Author(s):

Ryuji Matsumoto ◽

Takashige Abe ◽

Junji Ishizaki ◽

Hiroshi Kikuchi ◽

Toru Harabayashi ◽

...

Keyword(s):

Prognostic Factors ◽

Clinical Practice ◽

Urothelial Carcinoma ◽

Real World ◽

Second Line ◽

Second Line Chemotherapy ◽

Metastatic Urothelial Carcinoma ◽

Line Chemotherapy

Download Full-text

Nivolumab demonstrates benefit over nomogram-predicted 12-month survival as salvage therapy for metastatic urothelial carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.6_suppl.451 ◽

2018 ◽

Vol 36 (6_suppl) ◽

pp. 451-451 ◽

Cited By ~ 1

Author(s):

Gregory Russell Pond ◽

Guru Sonpavde ◽

Matt D. Galsky ◽

Padmanee Sharma ◽

Jonathan E. Rosenberg ◽

...

Keyword(s):

Prognostic Factors ◽

Urothelial Carcinoma ◽

Salvage Therapy ◽

Group Performance ◽

Checkpoint Inhibitors ◽

Statistical Significance ◽

Performance Status ◽

Eastern Cooperative Oncology Group ◽

Progression Free Survival ◽

Metastatic Urothelial Carcinoma

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.

Download Full-text

Prognostic factors for patients with metastatic urothelial carcinoma treated with cisplatin and 5-fluorouracil-based regimens

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.14583 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 14583-14583

Author(s):

Y. Tsai ◽

C. Lin ◽

C. Hsu ◽

K. Huang ◽

C. Huang ◽

...

Keyword(s):

Risk Factors ◽

Alkaline Phosphatase ◽

Prognostic Factors ◽

Urothelial Carcinoma ◽

Median Survival ◽

Survival Duration ◽

Visceral Metastasis ◽

Term Survival ◽

Significant Difference ◽

Metastatic Urothelial Carcinoma

14583 Background: Combination of cisplatin and 5-fluorouracil (5-FU) has activity in metastatic urothelial carcinoma (UC). To identify patient subgroups most likely to benefit and compare survival to that in previously described patient series, long-term survival, as a function of known and suspected prognostic variables, was determined. Methods: The survival status of 79 patients with metastatic urothelial cancer treated on two phase II trials of cisplatin and 5-FU-based regimens was updated. P-HDFL regimen (n = 35) was cisplatin 35 mg/m2 IV 24hr D1, 8; 5-FU 2,600 mg/m2 and leucovorin 300 mg/m2 IV 24hr D1, 8, 15; repeated every 28 days (Cancer 2006, in press). TP-HDFL regimen (n = 44) was paclitaxel 70 mg/m2 IV 1hr D1, 8; cisplatin 35 mg/m2 IV 24hr D1, 8; 5-FU 2,000 mg/m2 and leucovorin 300 mg/m2 IV 24hr D1, 8; repeated every 21 days (Proc ASCO 22:407b, 2003 [abstr 1637]). Univariate and multivariate Cox proportional hazards models were constructed. Results: Karnofsky performance status (KPS) <80%, presence of visceral metastasis, and alkaline phosphatase ≥220 U/l are three significant poor prognostic factors for survival. The percentage of patients who harbored zero-risk, one- or two-risk, and three-risk categories was 27%, 61%, and 13%, respectively. Among patients with no risk factors, the median survival time was not reached yet after a median follow-up of 43.0 months. Patients with one or two risk factors had a median survival duration of 12.3 months (95% CI 8.6–16.0). Patients with all three risk factors had a median survival of 4.6 months (95% CI 1.4–7.9). There was a significant difference in survival between the three groups (P < .0001). Conclusions: Previously described prognostic factors, including KPS <80%, visceral metastasis, and alkaline phosphatase ≥220 U/l, for survival in metastatic UC were confirmed in patients treated with cisplatin and 5-FU-based regimen. No significant financial relationships to disclose.

Download Full-text