TY - JOUR
T1 - Time from prior chemotherapy enhances prognostic risk grouping in the second-line setting of advanced urothelial carcinoma
T2 - A retrospective analysis of pooled, prospective phase 2 trials
AU - Sonpavde, Guru
AU - Pond, Gregory R.
AU - Fougeray, Ronan
AU - Choueiri, Toni K.
AU - Qu, Angela Q.
AU - Vaughn, David J.
AU - Niegisch, Guenter
AU - Albers, Peter
AU - James, Nicholas D.
AU - Wong, Yu Ning
AU - Ko, Yoo Joung
AU - Sridhar, Srikala S.
AU - Galsky, Matthew D.
AU - Petrylak, Daniel P.
AU - Vaishampayan, Ulka N.
AU - Khan, Awais
AU - Vogelzang, Nicholas J.
AU - Beer, Tomasz M.
AU - Stadler, Walter M.
AU - O'Donnell, Peter H.
AU - Sternberg, Cora N.
AU - Rosenberg, Jonathan E.
AU - Bellmunt, Joaquim
N1 - Funding Information:
Financial disclosures: Joaquim Bellmunt certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: G. Sonpavde, N.J. Vogelzang, W.M. Stadler, P.H. O’Donnell, and D.J. Vaughn have received research support from Boehringer-Ingelheim. R Fougeray is an employee of Pierre-Fabre. T.K. Choueiri, A.Q. Qu, J.E. Rosenberg, and G. Sonpavde have received research support from AstraZeneca. N.D. James, D.J. Vaughn, and J.M. Bellmunt have received research support from Pierre-Fabre. N.D. James also has received speaker fees from Pierre-Fabre. Y.N. Wong has received research support from BMS. Y. Ko, S. Sridhar, and G. Sonpavde have received research support from Celgene. U.N. Vaishampayan and W.M. Stadler have received research support from GSK, and G. Sonpavde has received speaker fees from GSK. M.D. Galsky has received research support from Eli Lilly. G. Niegisch and P. Albers have received research support from Eli Lilly and BMS.
PY - 2013/4
Y1 - 2013/4
N2 - Background: Outcomes for patients in the second-line setting of advanced urothelial carcinoma (UC) are dismal. The recognized prognostic factors in this context are Eastern Cooperative Oncology Group (ECOG) performance status (PS) >0, hemoglobin level (Hb) <10 g/dl, and liver metastasis (LM). Objectives: The purpose of this retrospective study of prospective trials was to investigate the prognostic value of time from prior chemotherapy (TFPC) independent of known prognostic factors. Design, setting, and participants: Data from patients from seven prospective trials with available baseline TFPC, Hb, PS, and LM values were used for retrospective analysis (n = 570). External validation was conducted in a second-line phase 3 trial comparing best supportive care (BSC) versus vinflunine plus BSC (n = 352). Outcome measurements and statistical analysis: Cox proportional hazards regression was used to evaluate the association of factors, with overall survival (OS) and progression-free survival (PFS) being the respective primary and secondary outcome measures. Results and limitations: ECOG-PS >0, LM, Hb <10 g/dl, and shorter TFPC were significant prognostic factors for OS and PFS on multivariable analysis. Patients with zero, one, two, and three to four factors demonstrated median OS of 12.2, 6.7, 5.1, and 3.0 mo, respectively (concordance statistic = 0.638). Setting of prior chemotherapy (metastatic disease vs perioperative) and prior platinum agent (cisplatin or carboplatin) were not prognostic factors. External validation demonstrated a significant association of TFPC with PFS on univariable and most multivariable analyses, and with OS on univariable analyses. Limitations of retrospective analyses are applicable. Conclusions: Shorter TFPC enhances prognostic classification independent of ECOG-PS >0, Hb <10 g/dl, and LM in the setting of second-line therapy for advanced UC. These data may facilitate drug development and interpretation of trials.
AB - Background: Outcomes for patients in the second-line setting of advanced urothelial carcinoma (UC) are dismal. The recognized prognostic factors in this context are Eastern Cooperative Oncology Group (ECOG) performance status (PS) >0, hemoglobin level (Hb) <10 g/dl, and liver metastasis (LM). Objectives: The purpose of this retrospective study of prospective trials was to investigate the prognostic value of time from prior chemotherapy (TFPC) independent of known prognostic factors. Design, setting, and participants: Data from patients from seven prospective trials with available baseline TFPC, Hb, PS, and LM values were used for retrospective analysis (n = 570). External validation was conducted in a second-line phase 3 trial comparing best supportive care (BSC) versus vinflunine plus BSC (n = 352). Outcome measurements and statistical analysis: Cox proportional hazards regression was used to evaluate the association of factors, with overall survival (OS) and progression-free survival (PFS) being the respective primary and secondary outcome measures. Results and limitations: ECOG-PS >0, LM, Hb <10 g/dl, and shorter TFPC were significant prognostic factors for OS and PFS on multivariable analysis. Patients with zero, one, two, and three to four factors demonstrated median OS of 12.2, 6.7, 5.1, and 3.0 mo, respectively (concordance statistic = 0.638). Setting of prior chemotherapy (metastatic disease vs perioperative) and prior platinum agent (cisplatin or carboplatin) were not prognostic factors. External validation demonstrated a significant association of TFPC with PFS on univariable and most multivariable analyses, and with OS on univariable analyses. Limitations of retrospective analyses are applicable. Conclusions: Shorter TFPC enhances prognostic classification independent of ECOG-PS >0, Hb <10 g/dl, and LM in the setting of second-line therapy for advanced UC. These data may facilitate drug development and interpretation of trials.
KW - Hemoglobin
KW - Liver metastasis
KW - Performance status
KW - Prognosis
KW - Second line
KW - Time from prior chemotherapy
KW - Urothelial carcinoma
UR - http://www.scopus.com/inward/record.url?scp=84874550179&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84874550179&partnerID=8YFLogxK
U2 - 10.1016/j.eururo.2012.11.042
DO - 10.1016/j.eururo.2012.11.042
M3 - Article
C2 - 23206856
AN - SCOPUS:84874550179
SN - 0302-2838
VL - 63
SP - 717
EP - 723
JO - European Urology
JF - European Urology
IS - 4
ER -