A nomogram including baseline prognostic factors to estimate the activity of second-line therapy for advanced urothelial carcinoma.
OBJECTIVE
To study the impact of the prognostic factors liver metastasis (LM), anaemia (haemoglobin [Hb] <10 g/dL), Eastern Cooperative Oncology Group performance status (ECOG-PS) ≥1 and time from previous chemotherapy (TFPC) on the activity of second-line therapy for advanced urothelial carcinoma (UC).


METHODS
Twelve phase II trials evaluating second-line chemotherapy and/or biological characteristics (n = 748) in patients with progressive disease were pooled. Progression-free survival (PFS) was defined as tumour progression or death from any cause. The PFS rate at 6 months (PFS6) was defined from the date of registration and calculated using the Kaplan-Meier method. Response rate (RR) was defined using Response Evaluation Criteria in Solid Tumours (RECIST) 1.0. A nomogram predicting PFS6 was constructed using the rms software package in R (http://www.r-project.org).


RESULTS
Data regarding progression, anaemia, LM, ECOG-PS and TFPC were available from 570 patients in nine phase II trials. The overall median PFS was 2.7 months, PFS6 was 22.2% (95% confidence interval 18.8-25.9) and the RR was 17.5% (95% CI: 14.5-20.9%). For every unit increase in risk group, the hazard of progression in 6 months increased by 41% and the odds of response decreased by 48%. A nomogram was constructed to predict PFS6 on an individual patient level. The model was internally validated and was shown to have acceptable calibration performance.


CONCLUSIONS
The RR and PFS6 vary as a function of baseline prognostic factors in patients receiving second-line therapy for advanced UC. A nomogram incorporating prognostic factors facilitates the evaluation of outcomes across phase II trials enrolling heterogeneous populations and helps select suitable agents for phase III testing.
Ontario Clinical Oncology Group, McMaster University, Hamilton, ON, Canada.
Gregory R
GR
Pond
Neeraj
N
Agarwal
Joaquim
J
Bellmunt
Toni K
TK
Choueiri
Angela
A
Qu
Ronan
R
Fougeray
David
D
Vaughn
Nicholas D
ND
James
Yacine
Y
Salhi
Peter
P
Albers
Günter
G
Niegisch
Matthew D
MD
Galsky
Yu-Ning
YN
Wong
Yoo-Joung
YJ
Ko
Walter M
WM
Stadler
Peter H
PH
O'Donnell
Srikala S
SS
Sridhar
Nicholas J
NJ
Vogelzang
Andrea
A
Necchi
Giuseppe
G
Di Lorenzo
Cora N
CN
Sternberg
Amitkumar
A
Mehta
Guru
G
Sonpavde
D000368:Aged; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000556:secondary; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary; D008297:Male; D008875:Middle Aged; D049451:Nomograms; D011379:Prognosis; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000473:pathology
advanced urothelial cancer; nomogram; progression-free survival at 6 months; response rate; second-line therapy