Dataset Information

Cabozantinib in metastatic renal cell carcinoma: latest findings and clinical potential.

ABSTRACT: Since the advent of immunotherapy revolutionized the treatment of metastatic renal cell carcinoma (mRCC), the attention of oncologists has been unavoidably shifted from tyrosine kinase inhibitors (TKIs) to immune checkpoint blockade, with the associated risk of listing cabozantinib as just one of many available TKIs. On the contrary, we think that cabozantinib represents a very good option for mRCC treatment, with outstanding outcomes in terms of response rate, progression-free survival, overall survival and quick time to treatment response. Its safety profile is acceptable and its discontinuation rate, due to toxicity, is similar to those of other TKIs. It is still not clear if the effectiveness of this drug is justified by its wide spectrum of multikinase activity, extended to the MET and AXL kinases, or by the simple maintenance of a 'vascular endothelial growth factor receptor pressure' after another previous TKI. Early-phase studies are currently ongoing to investigate the potential activity and safety of cabozantinib in association with immunotherapy, albeit with the risk of an overly toxic combination. Thus, future opportunities to improve the clinical use of this drug will probably be represented by a smart treatment sequence.

SUBMITTER: Bersanelli M

PROVIDER: S-EPMC5613858 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Cabozantinib in metastatic renal cell carcinoma: latest findings and clinical potential.

Bersanelli Melissa M Buti Sebastiano S

Therapeutic advances in medical oncology 20170802 10

Since the advent of immunotherapy revolutionized the treatment of metastatic renal cell carcinoma (mRCC), the attention of oncologists has been unavoidably shifted from tyrosine kinase inhibitors (TKIs) to immune checkpoint blockade, with the associated risk of listing cabozantinib as just one of many available TKIs. On the contrary, we think that cabozantinib represents a very good option for mRCC treatment, with outstanding outcomes in terms of response rate, progression-free survival, overall ...[more]

PMID: 28974985

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Project description:Renal-cell carcinoma (RCC) affects over 330,000 new patients every year, of whom 1/3 present with metastatic RCC (mRCC) at diagnosis. Most mRCC patients treated with a first-line agent relapse within 1 year and need second-line therapy. The present study aims to compare overall survival (OS) between nivolumab and cabozantinib from two recent pivotal studies comparing, respectively, each one of the two emerging treatments against everolimus in patients who relapse following first-line treatment. Comparison is traditionally carried out using the Bucher method, which assumes proportional hazard. Since OS curves intersected in one of the pivotal studies, models not assuming proportional hazards were also considered to refine the comparison. Four Bayesian parametric survival network meta-analysis models were implemented on overall survival (OS) data digitized from the Kaplan-Meier curves reported in the studies. Three models allowing hazard ratios (HR) to vary over time were assessed against a fixed-HR model. The Bucher method favored cabozantinib, with a fixed HR for OS vs. nivolumab of 1.09 (95% confidence interval: [0.77, 1.54]). However, all models with time-varying HR showed better fits than the fixed-HR model. The log-logistic model fitted the data best, exhibiting a HR for OS initially favoring cabozantinib, the trend inverting to favor nivolumab after month 5 (95% credible interval <1 from 10 months). The initial probability of cabozantinib conferring superior OS was 54%, falling to 41.5% by month 24. Numerical differences in study-adjusted OS estimates between the two treatments remained small. This study evidences that HR for OS of nivolumab vs. cabozantinib varies over time, favoring cabozantinib in the first months of treatment but nivolumab afterwards, a possible indication that patients with poor prognosis benefit more from cabozantinib in terms of survival, nivolumab benefiting patients with better prognosis. More evidence, including real-world observational data, is needed to compare effectiveness between cabozantinib and nivolumab.

Dataset Information

Cabozantinib in metastatic renal cell carcinoma: latest findings and clinical potential.

Publications

Cabozantinib in metastatic renal cell carcinoma: latest findings and clinical potential.

Similar Datasets

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