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

Abstract

Submit your article to this journal 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 ¼ 0.008) (HR for OS: 1.724; p ¼ 0.037) and Fuhrman grade 1-2 tumors (HR for OS: 2.198; p ¼ 0.007). Markers associated with poorer outcome on second-line therapy were: elevated serum lactate dehydrogenase (LDH) levels (HR for PFS: 0.511; p ¼ 0.04) (HR for OS: 0.392; p ¼ 0.017), low albumin (HR for OS: 0.392; p ¼ 0.01) and elevated corrected calcium levels (HR for OS: 0.416; p ¼ 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.

Prognostic Significance of Early Tumor Shrinkage Under Second-Line Targeted Therapy for Metastatic Renal Cell Carcinoma: A Retrospective Multi-Institutional Study in Japan

“…In this series, the median OS in the 271 patients included in this study was 24.8 months, which seems to be comparable or even superior to those in previous studies showing the prognosis of mRCC patients treated with second-line targeted agents [24]. Moreover, this study showed for the first time that the degree of ETS under second-line targeted therapy was proportional to OS among the four subgroups; that is, the median OS stratified according to the degree of ETS, as described above, was 45.8, 30.9, 22.1 and 14.2 months, respectively.…”

“…TKIs vs. mTOR inhibitors) failed to show independent impact on OS in the 271 patients. Despite limited findings regarding the prognostic factors in mRCC patients treated with second-line agents, currently available data suggest that traditional prognostic parameters in patients treated with first-line targeted agents could be applied to those receiving second-line therapy [24]. In fact, Ko et al recently reported that the IMDC prognostic model can be applied to mRCC patients receiving second-line targeted therapy in addition to previously validated populations undergoing first-line targeted therapy [25].…”

“…At our institutions, the first radiological examination was usually conducted at 4-8 weeks after initiating second-line therapy; thus, we calculated the degree of changes in tumor size at this point as ETS by stratifying the included patients into four subgroups according to our previous study [20], and revealed that 26 (9.6 %), 70 (25.8 %) and 84 (31.0 %) patients were judged to have achieved tumor shrinkage from -100 to -50 %, -49 to -25 % and -24 to 0 %, respectively, while the remaining 91 (33.6 %) showed a gain in the SLD. The degrees of tumor remission evaluated as the best response in previously reported studies varied according to the targeted agents used in second-line therapy [24]; therefore, the status of ETS achieved by each agent was subsequently analyzed, revealing significantly different distributions of ETS, showing axitinib, sunitinib, temsirolimus or sorafenib, and everolimus in decreasing order of the favorable status.…”

Predictive Factors for Second-Line Therapy in Metastatic Renal Cell Carcinoma: A Retrospective Analysis

“…The study of Sacré et al (15) identified grading to be a prognostic factor at the start of second-line therapy. To our knowledge, there is no study so far that has identified pretreatment tumor grade as the predictor of eligibility to receive second-line therapy.…”

A study of comparison between ionized calcium and albumin corrected calcium in patients with chronic kidney disease

“…Although some other studies were reported that non-corrected and albumin corrected that total calcium levels weak predictors of calcium levels in CKD subjects. 8 Hence the present study compare the values of Ionized calcium along with Total and Albumin corrected calcium levels with CKD subjects.…”