Cabozantinib, nivolumab ‘bring hope’ for advanced RCC patients

Oct 6 2015

By Lynda Williams, Senior medwireNews Reporter

Clinical trial results suggest significant benefits with the use of cabozantinib or nivolumab over everolimus for patients with advanced renal cell carcinoma (RCC), researchers reported at the European Cancer Congress in Vienna, Austria.

Findings from the two studies of patients with clear cell histology and disease progression while using vascular endothelial growth factor receptor (VEGFR) inhibitor therapy were reported simultaneously in The New England Journal of Medicine.

Toni Choueiri, from Dana–Farber Cancer Institute in Boston, Massachusetts, USA, presented findings for the first 375 patients enrolled into the phase III, open label, randomised METEOR trial.

After a minimum of 11 months, the primary endpoint of estimated progression-free survival (PFS) was a median of 7.4 months for the 187 patients given cabozantinib (60 mg/day), an oral, small molecular inhibitor of tyrosine kinases including MET, VEGFRs and AXL.

This was significantly longer than the 3.8 months achieved by the 188 patients treated with the mTOR inhibitor everolimus 10 mg/day, giving a significant hazard ratio (HR) for death of 0.58.

Cabozantinib-treated patients also had a significantly higher objective response rate than those given everolimus (21 vs 5%).

And although there was insufficient follow-up at a planned interim analysis a minimum of 7 months after starting treatment to show a significant increase in overall survival (OS) with cabozantinib compared with everolimus, the researchers say there was a “strong trend” with an HR of 0.67 indicating that this benefit may emerge after longer follow-up.

Presenting the CheckMate 025 study, Padmanee Sharma, from MD Anderson Cancer Center in Houston, Texas, USA, reported that the trial was halted when the planned interim analysis demonstrated superior OS for patients given the programmed cell death 1 (PD-1) inhibitor nivolumab on a 3 mg intravenous regimen.

This primary endpoint was a median of 25.0 months for the 410 nivolumab-treated patients versus 19.6 months for 411 patients given everolimus 10 mg/kg per day, giving a significant HR for death of 0.73.

Objective response rate was also significantly higher in the nivolumab group, at 25% versus 5% for the everolimus group and an odds ratio of 5.98.

And although median PFS was not significantly higher with nivolumab, at 4.6 months compared with 4.4 months in the everolimus-treated patients, there was “late separation” of the curve indicating the possibility of a delayed benefit in the nivolumab group.

Speaking to medwireNews at a press conference, Sharma noted that there are not yet biomarkers to identify which patients will benefit from nivolumab.

Programmed death ligand 1 (PD-L1) expression before treatment was comparable between the treatment arms and was not associated with OS, prompting Sharma to comment in a press release “that PD-L1 expression should not be used to determine which patients might respond to the therapy and whether or not to offer it to them.”

Nevertheless, explaining that PD-L1 is a “dynamic” biomarker of immune response, she added: “I would expect that tumour samples taken while patients were on-treatment, as opposed to pre-treatment, might indicate that PD-L1 expression, as well as other markers of immune response, has a correlation with response to treatment.”

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