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.
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.
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.
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.
Acta oncologica (Stockholm, Sweden). 2015 Oct 23 [Epub ahead of print]
Anne Sacré, Philippe Barthélémy, Clement Korenbaum, Mickael Burgy, Pascal Wolter, Herlinde Dumez, Evelyne Lerut, Tine Loyson, Steven Joniau, Raymond Oyen, Philip R Debruyne, Patrick Schöffski, Benoit Beuselinck
a Department of General Medical Oncology , University Hospitals Leuven, Leuven Cancer Institute, KU Leuven , Leuven , Belgium . , b Department of Medical Oncology , Centre Hospitalier Régional Universitaire , Strasbourg , France . , b Department of Medical Oncology , Centre Hospitalier Régional Universitaire , Strasbourg , France . , b Department of Medical Oncology , Centre Hospitalier Régional Universitaire , Strasbourg , France . , a Department of General Medical Oncology , University Hospitals Leuven, Leuven Cancer Institute, KU Leuven , Leuven , Belgium . , a Department of General Medical Oncology , University Hospitals Leuven, Leuven Cancer Institute, KU Leuven , Leuven , Belgium . , d Department of Pathology , University Hospitals Leuven, KU Leuven , Leuven , Belgium . , e Department of Medical Oncology , AZ Groeninge , Kortrijk , Belgium . , f Department of Urology , University Hospitals Leuven, KU Leuven , Leuven , Belgium . , g Department of Radiology , University Hospitals Leuven, KU Leuven , Leuven , Belgium , and. , e Department of Medical Oncology , AZ Groeninge , Kortrijk , Belgium . , a Department of General Medical Oncology , University Hospitals Leuven, Leuven Cancer Institute, KU Leuven , Leuven , Belgium . , a Department of General Medical Oncology , University Hospitals Leuven, Leuven Cancer Institute, KU Leuven , Leuven , Belgium .