Prognostic Factors of Survival for Patients With Metastatic Renal Cell Carcinoma With Brain Metastases Treated With Targeted Therapy: Results From the International Metastatic Renal Cell Carcinoma Database Consortium

Vickers, Michael M.; Alharbi, Homood; Choueiri, Toni K.; Kollmannsberger, Christian; North, Scott; MacKenzie, Mary J.; Knox, Jennifer J.; Rini, Brian I.; Heng, Daniel Y.C.

doi:10.1016/j.clgc.2013.04.012

Cited by 67 publications

(59 citation statements)

References 18 publications

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“…The IMDC and MSKCC prognostic scores were calculated at start of second-line therapy, as well as the different factors that form the basis for these established scores (interval between diagnosis and systemic treatment, performance status, hemoglobin levels, corrected serum calcium levels, serum LDH levels, neutrophil and platelet count), presence of sarcomatoid dedifferentiation in 25% of the tumor volume [12], PFS [13] and best response on first-line therapy, the presence of bone metastases [14], brain metastases [15] or glandular metastases (defined as pancreatic, adrenal or thyroid metastases) [16], baseline C-reactive protein (CRP) levels ( or4inferior limit of normal, 5 mg/dl) [17] and albumin levels ( or4inferior limit of normal, 3.5 g/dl) [18,19] at start of second-line therapy. Associations between PFS or OS and potential prognostic factors were assessed using Kaplan-Meier estimates and the logrank test in univariate analysis.…”

Section: Methodsmentioning

confidence: 99%

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

Sacré

Barthélémy²,

Korenbaum³

et al. 2015

Acta Oncologica

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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.

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Section: Methodsmentioning

confidence: 99%

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

Sacré

Barthélémy²,

Korenbaum³

et al. 2015

Acta Oncologica

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“…31 In a larger retrospective study of patients with brain metastatic RCC in the era of VEGFR-targeted KI, >4 brain metastases, KPS < 80%, and an interval of >1 year from diagnosis of brain metastases to initiation of targeted therapy were associated with decreased OS. 3 We showed that on univariate analysis, >1 brain metastasis was a poor prognostic factor. Decreasing performance status was a negative prognostic factor in studies both before and after the advent of targeted therapy; however, KPS alone was not a prognostic factor in this cohort.…”

Section: Discussionmentioning

confidence: 97%

“…Decreasing performance status was a negative prognostic factor in studies both before and after the advent of targeted therapy; however, KPS alone was not a prognostic factor in this cohort. 1,3 The DS-GPA score though does include the KPS as 1 of its 2 components. A study in the era before targeted therapy showed extracranial metastases to be a negative prognostic factor in patients with brain metastatic RCC.…”

Section: Discussionmentioning

confidence: 99%

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Radiotherapy for Brain Metastases From Renal Cell Carcinoma in the Targeted Therapy Era

Bates

Youn²,

Peterson³

et al. 2017

American Journal of Clinical Oncology

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This hypothesis-generating analysis suggests among patients with brain metastatic RCC treated with the most current therapies, those selected to undergo SRS did not experience significantly different survival or control outcomes than those selected to undergo WBRT. From our experience to date, limited in patient numbers, there seems to be neither harm nor benefit in using concurrent KI therapy during radiotherapy. Given that most patients progress systemically, we would recommend considering KI use during brain radiotherapy in these patients.

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“…However, no intracranial responses were observed, indicating that targeted therapies alone might only have minor impact in newly diagnosed BM of renal cell carcinoma [78]. Some small case series further postulate efficacy of the VEFG antibody bevacizumab in patients with BM from renal cell carcinoma [79,80].…”

Section: • • Targeted Therapy Approaches In Melanoma Brain Metastasesmentioning

confidence: 88%

The Future of Targeted Therapies for Brain Metastases

Berghoff

2015

Future Oncol.

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Brain metastases (BM) are an increasing challenge in the management of patients with advanced cancer. Treatment options for BM are limited and mainly focus on the application of local therapies. Systemic therapies including targeted therapies are only poorly investigated, as patients with BM were frequently excluded from clinical trials. Several targeted therapies have shown promising activity in patients with BM. In the present review we discuss existing and emerging targeted therapies for the most frequent BM primary tumor types. We focus on challenges in the conduction of clinical trials on targeted therapies in BM patients such as patient selection, combination with radiotherapy, the obstacles of the blood-brain barrier and the definition of study end points.

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Prognostic Factors of Survival for Patients With Metastatic Renal Cell Carcinoma With Brain Metastases Treated With Targeted Therapy: Results From the International Metastatic Renal Cell Carcinoma Database Consortium

Cited by 67 publications

References 18 publications

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

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

Radiotherapy for Brain Metastases From Renal Cell Carcinoma in the Targeted Therapy Era

The Future of Targeted Therapies for Brain Metastases

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