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

Harada, Kiyoshi; Ozono, Seiichiro; Fujisawa, Masato

doi:10.1007/s40291-016-0206-3

Cited by 7 publications

(6 citation statements)

References 29 publications

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“…ETS and survival outcome. In the MTT era, as previously suggested (11,16), eTS is another predictive factor in mRCC patients. Among mRCC patients, eTS data was available in 127 patients (Table I).…”

Section: Impact Of Ets On Survival Outcome In Mrcc Patientsmentioning

confidence: 76%

Early tumor shrinkage as a predictive factor of metastatic renal cell carcinoma in molecular targeted therapy: A single institutional study

et al. 2018

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The aim of the present study was to investigate the impact of metastatic sites and early tumor shrinkage (eTS) as prognostic predictive factors of metastatic renal cell carcinoma (mRCC) in molecular targeted therapy. A total of 209 advanced RCC cases treated with sorafenib, sunitinib, axitinib, pazopanib, temsirolimus and everolimus from our single institution were included in the present study. Several known prognostic predictive factors, including metastatic sites and the rate of eTS, were analyzed by Kaplan-Meier survival estimate analysis followed by Cox's proportional hazards model analysis. eTS was measured by three independent physicians. Four metastatic sites in the liver, bone, lymph nodes and brain as well as greater eTS were identified as potential independent predictors of overall survival (OS) in several cohorts: i) Metastatic RCC (n=194); ii) metastatic clear cell RCC (n=119); and iii) mRCC patients with eTS data (n=127). In sub-analyses of patients treated with each 1st line tyrosine kinase inhibitor, eTS was identified as a potentially potent predictor of OS in patients treated with axitinib. The liver, bone, lymph nodes, brain metastases and eTS were identified as independent predictive factors of OS by analyzing a limited Japanese cohort.

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Section: Impact Of Ets On Survival Outcome In Mrcc Patientsmentioning

confidence: 76%

Early tumor shrinkage as a predictive factor of metastatic renal cell carcinoma in molecular targeted therapy: A single institutional study

et al. 2018

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“…With respect to benefits for patient outcomes, our model is likely to predict the best ORR and several AEs. Best ORR is used as a surrogate biomarker for overall survival in advanced and metastatic RCC [ 20 , 21 ], while higher AUC did not reach significance to predict progression-free survival (PFS) and overall survival (OS) in a titration study [ 22 , 23 ]. The lack of an association with PFS and OS in the titration study may be explained by the wide variation in individual AUC values for axitinib treatment, indicating that optimal initial dosing should be determined based on PK data.…”

Section: Discussionmentioning

confidence: 99%

Pharmacogenetics-based area-under-curve model can predict efficacy and adverse events from axitinib in individual patients with advanced renal cell carcinoma

et al. 2018

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We investigated the relationship between axitinib pharmacogenetics and clinical efficacy/adverse events in advanced renal cell carcinoma (RCC) and established a model to predict clinical efficacy and adverse events using pharmacokinetic and gene polymorphisms related to drug metabolism and efflux in a phase II trial. We prospectively evaluated the area under the plasma concentration–time curve (AUC) of axitinib, objective response rate, and adverse events in 44 consecutive advanced RCC patients treated with axitinib. To establish a model for predicting clinical efficacy and adverse events, polymorphisms in genes including ABC transporters (ABCB1 and ABCG2), UGT1A, and OR2B11 were analyzed by whole-exome sequencing, Sanger sequencing, and DNA microarray. To validate this prediction model, calculated AUC by 6 gene polymorphisms was compared with actual AUC in 16 additional consecutive patients prospectively. Actual AUC significantly correlated with the objective response rate (P = 0.0002) and adverse events (hand-foot syndrome, P = 0.0055; and hypothyroidism, P = 0.0381). Calculated AUC significantly correlated with actual AUC (P < 0.0001), and correctly predicted objective response rate (P = 0.0044) as well as adverse events (P = 0.0191 and 0.0082, respectively). In the validation study, calculated AUC prior to axitinib treatment precisely predicted actual AUC after axitinib treatment (P = 0.0066). Our pharmacogenetics-based AUC prediction model may determine the optimal initial dose of axitinib, and thus facilitate better treatment of patients with advanced RCC.

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“…As it takes a relatively short time to reveal the efficacy of TKI, we can evaluate the response early. ETS is also useful as a prognostic factor after second‐line TKI therapy . The concept of ETS is thought to be reasonable considering the characteristics of TKI, and it is useful to assess the tumor response and prognosis of mRCC when we use TKI in daily clinical practice.…”

Section: Prognostic Factors For Mrcc Patients Treated With Targeted Tmentioning

confidence: 99%

Current status of prognostic factors in patients with metastatic renal cell carcinoma

et al. 2019

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In recent years, the induction of novel agents, including molecular‐targeted agents and immune checkpoint inhibitors, have dramatically changed therapeutic options and their outcomes for metastatic renal cell carcinoma. Several prognostic models based on the data of patients with metastatic renal cell carcinoma treated with targeted agents or cytokine therapy have been useful in real clinical practice. Serum or peripheral blood markers related to inflammatory response have been reported to be associated with their prognosis or therapeutic efficacy. In addition to them, investigation for novel predictive factors that represent the efficacy of agents, the risk of adverse events and the prognosis are required for the advance of therapeutic strategies. The present review discusses the conventional prognostic models and clinical factors, and recent advances of the identification of some of the most promising molecules as novel biomarkers for metastatic renal cell carcinoma.

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

Abstract: These findings suggest that ETS at the first post-baseline assessment under treatment with a second-line targeted agent could serve as a useful parameter with an independent impact on OS in mRCC patients receiving second-line targeted therapy.

Cited by 7 publications

References 29 publications

Early tumor shrinkage as a predictive factor of metastatic renal cell carcinoma in molecular targeted therapy: A single institutional study

Early tumor shrinkage as a predictive factor of metastatic renal cell carcinoma in molecular targeted therapy: A single institutional study

Pharmacogenetics-based area-under-curve model can predict efficacy and adverse events from axitinib in individual patients with advanced renal cell carcinoma

Current status of prognostic factors in patients with metastatic renal cell carcinoma

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