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ECC 2015: Nivolumab Improves Overall Survival in Patients With Advanced Kidney Cancer

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Key Points

  • Patients taking nivolumab had a median overall survival of 25 months, compared with 19.6 months for those taking everolimus.
  • The objective response rate was 25% for nivolumab vs 5.4% for everolimus, the partial response rate was 24.1% vs 4.9%, and the complete response rate was 1% vs 0.5%, respectively.
  • Deaths had occurred among 45% of patients receiving nivolumab and 54% of patients receiving everolimus, and the risk of death from any cause was 27% lower among the nivolumab patients.

The targeted drug nivolumab (Opdivo) significantly prolonged survival in patients with advanced kidney cancer whose disease had progressed after their first treatment, according to the results (Abstract 3LBA) presented at the 2015 European Cancer Congress (ECC) in Vienna, Austria, and published simultaneously by Motzer et al in The New England Journal of Medicine.

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 tumors.

Improved Survival and Response Rates

Padmanee Sharma, MD, PhD, Scientific Director of the Immunotherapy Platform and Professor in the Departments of Genitourinary Medical Oncology and Immunology at the MD Anderson Cancer Center, explained in the presidential session at the 2015 European Cancer Congress, “CheckMate 025 is the first and only study in which immunotherapy with an immune checkpoint inhibitor, used after prior treatment has failed, has shown a benefit in overall survival among patients with advanced kidney cancer for whom treatment options are currently limited. This analysis shows that 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 show that a greater proportion of patients had tumors that shrank in response to nivolumab than to everolimus. The objective response rate was 25% for nivolumab vs 5.4% for everolimus; the partial response rate was 24.1% vs 4.9%; the complete response rate was 1% vs 0.5%, respectively; and many other patients experienced stable disease when the tumours did not grow—34.4% for nivolumab-treated patients vs 55.2% for everolimus-treated patients.”

“It is exciting to see the outcome of this study, as the results are significant and clinically meaningful to patients and healthcare professionals alike. They are likely to change the treatment of patients with advanced kidney cancer, whose disease has progressed on prior treatment. Although we cannot speculate at this time on when nivolumab might enter the clinic, we hope that this study will quickly lead to approval of nivolumab as a standard of care therapy for these patients,” said the researchers.

Study Details

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 randomly assigned to receive 3 mg/kg of nivolumab intravenously every 2 weeks or a 10-mg tablet of everolimus taken orally once a day. They were followed for a minimum of 15 months, and the data cutoff point for the analysis presented was June 2015, at which point 17% of patients receiving nivolumab and 7% of patients receiving everolimus remained on treatment. Deaths had occurred among 45% of patients receiving nivolumab and 54% of patients receiving everolimus, and the risk of death from any cause was 27% lower among nivolumab patients.

There were fewer serious (grade 3-4) side effects among patients treated with nivolumab: 19% compared with 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 anemia (24%) for everolimus. There were no treatment-related deaths for nivolumab, and two treatment-related deaths among patients receiving everolimus.

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.

Dr. Sharma said, “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 5-year survival rate for those diagnosed with advanced kidney cancer is 12.1%, and so more effective treatments are desperately needed for these patients.”

“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 and whether or not to offer it to them,” she continued. “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 tumor samples before treatment does not capture the true expression of PD-L1 and how it may correlate to responses to treatment. I would expect that tumor samples taken while patients were on treatment, as opposed to pretreatment, might indicate that PD-L1 expression, as well as other markers of immune response, has a correlation with response to treatment.” 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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