Clinical outcomes by nephrectomy status in METEOR, a randomized phase 3 trial of cabozantinib versus everolimus in patients with advanced renal cell carcinoma Journal Article


Authors: Tannir, N. M.; Powles, T.; Escudier, B.; Donskov, F.; Grunwald, V.; Sternberg, C. N.; Schmidinger, M.; Schoffski, P.; Szczylik, C.; Peltolta, K.; Nosov, D.; Melichar, B.; Clary, D.; Scheffold, C.; Motzer, R. J.; Choueiri, T. K.
Article Title: Clinical outcomes by nephrectomy status in METEOR, a randomized phase 3 trial of cabozantinib versus everolimus in patients with advanced renal cell carcinoma
Abstract: Background: We investigated outcomes with cabozantinib versus everolimus in patients with advanced renal cell carcinoma (RCC) with or without prior nephrectomy in the phase 3 METEOR trial (NCT01865747). Methods: Patients (N = 658) with advanced clear cell RCC and prior treatment with >= 1 VEGFR tyrosine kinase inhibitor (TKI) were randomized to cabozantinib 60 mg/day or everolimus 10 mg/day. Pre-specified subgroup analyses of progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were conducted by prior nephrectomy status. Response was assessed by independent radiology committee. Results: Most enrolled patients (85%) had prior nephrectomy. Baseline prognostic factors (e.g. MSKCC risk group) were less favorable for patients without prior nephrectomy. Cabozantinib improved outcomes versus everolimus in the subgroups with and without nephrectomy-hazard ratios (95% CIs) of 0.51 (0.41-0.64) and 0.51 (0.30-0.86), respectively, for PFS, and 0.66 (0.52-0.84) and 0.75 (0.44-1.27), respectively, for OS. Median OS was numerically longer in patients with versus those without prior nephrectomy in both treatment arms. ORR for cabozantinib versus everolimus was 17% versus 4% for the prior nephrectomy subgroup and 21% versus 2% for the subgroup without prior nephrectomy. Among evaluable patients without prior nephrectomy, reductions of renal target lesions occurred in 94% (16/17) of patients in the cabozantinib arm versus 44% (8/18) in the everolimus arm. The safety profiles of both subgroups were generally consistent with that of the overall study population. Conclusion: Cabozantinib improved PFS, ORR, and OS compared with everolimus in patients with advanced RCC irrespective of nephrectomy status.
Keywords: survival; sunitinib; renal cell carcinoma; nephrectomy; targeted therapy; axitinib; everolimus; interferon-alpha; efficacy; endothelial growth-factor; cytoreductive nephrectomy; 2nd-line treatment; open-label; cabozantinib
Journal Title: Kidney Cancer
Volume: 4
Issue: 1
ISSN: 2468-4562
Publisher: IOS Press  
Date Published: 2020-03-30
Start Page: 29
End Page: 39
Language: English
ACCESSION: WOS:000664215700004
DOI: 10.3233/kca-190080
PROVIDER: wos
Notes: Article -- Source: Wos
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  1. Robert Motzer
    1243 Motzer