Outcomes from Second-Line Therapy in Long-Term Responders to First-Line Tyrosine Kinase Inhibitor in Clear-Cell Metastatic Renal Cell Carcinoma.
Fiche publication
Date publication
décembre 2014
Auteurs
Membres identifiés du Cancéropôle Est :
Dr EYMARD Jean-Christophe
Tous les auteurs :
Elaidi R, Harbaoui A, Beuselinck B, Eymard JC, Bamias A, De Guillebon E, Porta C, Vano Y, Linassier C, Debruyne PR, Gross-Goupil M, Ravaud A, Aitelhaj M, Marret G, Oudard S
Lien Pubmed
Résumé
BACKGROUND: Although sequential targeted therapy is standard in patients with metastatic clear-cell renal cell carcinoma (m-ccRCC), the choice of drugs and optimal administration sequence have yet to be established. The objective of this study was to explore whether it is preferable to rechallenge a long-term responder to a first-line tyrosine kinase inhibitor (TKI) with a TKI or whether to switch to a mammalian target of rapamycin inhibitor (mTORi); to determine whether second-line treatment response depends on duration of first-line response (TD1). PATIENTS AND METHODS: Retrospective multicenter study (2004-2011) of 241 consecutive mRCC patients (clear-cell histology) who received a first-line TKI for >/=6 months followed by a second-line TKI (n=118) or mTORi (n=123). Endpoints: Progression-free survival (PFS) and time-to-treatment-failure (TTF) on second-line therapy. Multivariable full-model covariables: second-line drug, TD1, ECOG-PS prior to first- and second line, best objective response (first-line), Fuhrman grade, number of metastatic sites, and presence of bone metastases. Adjustment covariable: International mRCC Database Consortium (IMDC) risk score. Multiple propensity score and missing data methods were used. Any correlation between first-line and second-line PFS was investigated using censored quantile regression models (CQRM). RESULTS: Sequence effect in the overall cohort was in favor of the TKI-TKI sequence over the TKI-mTORi sequence on using TD1 as continuous covariable (HR approximately 0.75 for PFS and TTF). TKI-TKI superiority was attributed in large part to the 11-22 month (TD1) subgroup of patients which displayed significantly better outcomes (HR approximately 0.5; median PFS (months): 9.4 (5.9-12.2) vs 3.9 (3.0-5.5), p=0.003; TTF(months): 8.0 (5.5-11.0) versus 3.6 (3.0-4.6), p=0.009). Upon full CQRM, long-term second-line responders were more likely to have received a second TKI than an mTORi and to have been long-term responders to first-line TKI. CONCLUSIONS: m-ccRCC patients who remained on first-line TKI between 11 and 22 months benefited from a TKI rechallenge rather than from second-line mTORi.
Référence
Ann Oncol. 2014 Dec 1. pii: mdu552.