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

Anne Sacré, Philippe Barthé Lémy, Clement Korenbaum, Mickael Burgy, Pascal Wolter, Herlinde Dumez, Evelyne Lerut, Tine Loyson, Steven Joniau, Raymond Oyen, Philip R. Debruyne, Patrick Schöffski, Benoit Beuselinck*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)329-340
Number of pages12
JournalActa Oncologica
Volume55
Issue number3
DOIs
Publication statusPublished - 1 Jan 2016

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Radiology, Nuclear Medicine and Imaging

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