Nivolumab ( Opdivo ), an anti-PD-1 immune checkpoint inhibitor, significantly prolongs survival in patients with advanced kidney cancer, whose disease has progressed after their first treatment, according to results presented at the 2015 European Cancer Congress and published simultaneously in the New England Journal of Medicine ( NEJM ).
The CheckMate 025 phase III clinical trial, which compared Nivolumab with the standard treatment, Everolimus ( Afinitor ), in patients with clear cell renal cell carcinoma, is the first to show an improvement in overall survival in these patients for any immune checkpoint inhibitor drug.
Nivolumab blocks the interaction between the programmed cell death protein 1 ( PD-1 ) and another molecule called programmed cell death protein ligand 1 ( PD-L1 ).
However, the survival benefit was seen in patients regardless of the extent of PD-L1 expression in their tumours.
Patients taking Nivolumab had a median overall survival of 25 months as compared to 19.6 months for those taking Everolimus.
Data from this analysis have shown that a greater proportion of patients had tumours that shrank in response to Nivolumab than to Everolimus; the objective response rate was 25% for Nivolumab versus 5.4% for Everolimus, the partial response rate was 24.1% versus 4.9%, the complete response rate was 1% versus 0.5% respectively, and many other patients experienced stable disease when the tumours did not grow – 34.4% for Nivolumab-treated patients versus 55.2% for Everolimus-treated patients.
There were fewer serious ( grade 3-4 ) side effects among patients treated with Nivolumab: 19% compared to 37% among patients treated with Everolimus.
The most common side effects were; fatigue ( 33% ), nausea ( 14% ) and severe itching ( 14% ) for Nivolumab, and fatigue ( 34% ), inflammation of the mucous membrane of the mouth ( 30% ) and anaemia ( 24% ) for Everolimus.
There were no treatment-related deaths for Nivolumab and two among patients receiving Everolimus.
The international CheckMate 025 phase III clinical trial recruited 821 patients with advanced clear cell kidney cancer, who had received prior treatment, between October 2012 and March 2014. They were randomised to receive 3 mg/kg of Nivolumab intravenously every two weeks or a 10 mg tablet of Everolimus taken orally once a day.
They were followed up for a minimum of 15 months and the data cut-off point for the analysis presented at ECC2015 was June 2015, at which point 17% of patients receiving Nivolumab and 7% of patients receiving Everolimus remained on the treatment.
Deaths had occurred among 45% of patients on Nivolumab and 54% of patients on Everolimus, and the risk of death from any cause was 27% lower among the Nivolumab patients.
The trial was stopped early in July 2015 when it became clear that there was superior overall survival among patients being treated with Nivolumab. Patients were offered the opportunity to continue with Nivolumab treatment or, for those on Everolimus, to switch to Nivolumab.
Renal cell carcinoma is the most common type of kidney cancer in adults, with 338,000 new cases and more than 100,000 deaths worldwide each year. Globally, the five-year survival rate for those diagnosed with advanced kidney cancer is 12.1%.
The finding that overall survival was higher among patients treated with Nivolumab, irrespective of PD-L1 expression, suggests that PD-L1 expression should not be used to determine which patients might respond to the therapy.
PD-L1 is a dynamic biomarker that changes over time as a result of evolving immune responses. So it is not surprising that PD-L1 measured in tumour samples before treatment does not capture the true expression of PD-L1 and how it may correlate to responses to treatment. ( Xagena )
Source: European Society for Medical Oncology ( ESMO ) Congress, 2015