TY - JOUR
T1 - Prognostic factors in second-line targeted therapy for metastatic clear-cell renal cell carcinoma after progression on an anti-vascular endothelial growth factor receptor tyrosine kinase inhibitor
AU - Sacré, Anne
AU - Barthé Lémy, Philippe
AU - Korenbaum, Clement
AU - Burgy, Mickael
AU - Wolter, Pascal
AU - Dumez, Herlinde
AU - Lerut, Evelyne
AU - Loyson, Tine
AU - Joniau, Steven
AU - Oyen, Raymond
AU - Debruyne, Philip R.
AU - Schöffski, Patrick
AU - Beuselinck, Benoit
N1 - Publisher Copyright:
© 2015 Taylor & Francis.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - Background: About 40% of metastatic clear-cell renal cell carcinoma (m-ccRCC) patients receive a second-line targeted therapy after failure of anti-vascular endothelial growth factor receptor tyrosine kinase inhibitors (anti-VEGFR-TKI). Efficacy of second-line therapy is usually limited and prognostic and predictive factors at the start of second-line therapy are lacking. To identify the subgroup of patients that will benefit from such treatment remains a challenge. Methods: We performed a multi-institutional, retrospective study of patients who received a second-line therapy after progression on an anti-VEGFR-TKI. Univariate and multivariate analyses were performed in order to identify prognostic factors for progressive disease (PD) as best response, progression-free survival (PFS) and overall survival (OS) on second-line therapy. Results: For the whole cohort of 108 patients, mOS from the start of second-line therapy was 8.9 months while mPFS on second-line therapy was 2.8 months. A total of 49/105 (47%) patients had PD, 50/105 (48%) stable disease (SD) and 6/105 (6%) a partial response (PR). On multivariate analysis, the following markers were associated with improved outcome on second-line therapy: a PFS on first-line therapy≥12 months (HR for PFS: 1.961; p=0.008) (HR for OS: 1.724; p=0.037) and Fuhrman grade 1-2 tumors (HR for OS: 2.198; p=0.007). Markers associated with poorer outcome on second-line therapy were: elevated serum lactate dehydrogenase (LDH) levels (HR for PFS: 0.511; p=0.04) (HR for OS: 0.392; p=0.017), low albumin (HR for OS: 0.392; p=0.01) and elevated corrected calcium levels (HR for OS: 0.416; p=0.01). The impact on OS of the Memorial Sloan Kettering Cancer Centre (MSKCC) and International Renal Cell Carcinoma Database Consortium (IMDC) prognostic scores as calculated at start of second-line therapy was validated in our patient series. Conclusions: Duration of first-line PFS, Fuhrman grade, serum LDH levels, albumin levels, corrected calcium levels and the MSKCC and IMDC scores calculated at start of second-line therapy are prognostic factors for m-ccRCC patients treated with second-line targeted therapy.
AB - Background: About 40% of metastatic clear-cell renal cell carcinoma (m-ccRCC) patients receive a second-line targeted therapy after failure of anti-vascular endothelial growth factor receptor tyrosine kinase inhibitors (anti-VEGFR-TKI). Efficacy of second-line therapy is usually limited and prognostic and predictive factors at the start of second-line therapy are lacking. To identify the subgroup of patients that will benefit from such treatment remains a challenge. Methods: We performed a multi-institutional, retrospective study of patients who received a second-line therapy after progression on an anti-VEGFR-TKI. Univariate and multivariate analyses were performed in order to identify prognostic factors for progressive disease (PD) as best response, progression-free survival (PFS) and overall survival (OS) on second-line therapy. Results: For the whole cohort of 108 patients, mOS from the start of second-line therapy was 8.9 months while mPFS on second-line therapy was 2.8 months. A total of 49/105 (47%) patients had PD, 50/105 (48%) stable disease (SD) and 6/105 (6%) a partial response (PR). On multivariate analysis, the following markers were associated with improved outcome on second-line therapy: a PFS on first-line therapy≥12 months (HR for PFS: 1.961; p=0.008) (HR for OS: 1.724; p=0.037) and Fuhrman grade 1-2 tumors (HR for OS: 2.198; p=0.007). Markers associated with poorer outcome on second-line therapy were: elevated serum lactate dehydrogenase (LDH) levels (HR for PFS: 0.511; p=0.04) (HR for OS: 0.392; p=0.017), low albumin (HR for OS: 0.392; p=0.01) and elevated corrected calcium levels (HR for OS: 0.416; p=0.01). The impact on OS of the Memorial Sloan Kettering Cancer Centre (MSKCC) and International Renal Cell Carcinoma Database Consortium (IMDC) prognostic scores as calculated at start of second-line therapy was validated in our patient series. Conclusions: Duration of first-line PFS, Fuhrman grade, serum LDH levels, albumin levels, corrected calcium levels and the MSKCC and IMDC scores calculated at start of second-line therapy are prognostic factors for m-ccRCC patients treated with second-line targeted therapy.
UR - http://www.scopus.com/inward/record.url?scp=84945152095&partnerID=8YFLogxK
U2 - 10.3109/0284186X.2015.1099731
DO - 10.3109/0284186X.2015.1099731
M3 - Article
C2 - 26494607
AN - SCOPUS:84945152095
SN - 0284-186X
VL - 55
SP - 329
EP - 340
JO - Acta Oncologica
JF - Acta Oncologica
IS - 3
ER -