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results
 
 

: CHECKMATE 025

 

Study of Nivolumab versus Everolimus in Pre-Treated Advanced or Metastatic Clear-cell Renal Cell Carcinoma (NCT01668784)
 
 
  reported September 2015

HOW MANY

people participated in the trial?

A total of 821 patients at 146 sites in 24 countries in North America, Europe, Australia, South America, and Asia took part in the trial.

STUDY

DESIGN

What did the study look like?

All participating patients were randomly divided into two groups. After this randomisation a total of 803 patients received treatment. 406 patients were treated with nivolumab (Opdivo™) alone, 397 patients were treated with everolimus (Afinitor™) alone:

  • nivolumab (Opdivo™) is a fully human monoclonal antibody targeting PD-1, not yet approved for RCC
  • everolimus (Afinitor™) is an oral, mTor-inhibitor and an approved treatment for RCC.

The two groups were evenly balanced on the basis of demographic and clinical characteristics of the patients The majority of patients (72%) had received one prior therapy for advanced renal-cell carcinoma.

Study Design Checkmate 025

1) Nivolumab was given intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity or withdrawal of consent.

2) Everolimus was taken by mouth daily until documented disease progression, discontinuation due to toxicity, withdrawal of consent.
 
For further information on the trial, please click here: Checkmate 025

RESULTS

of the study

The trial aimed to answer several questions:
  1. Will the new treatment (nivolumab) show a better overall survival (which was defined as the time from randomisation to the date of death)?
  2. How many patients will respond to each therapy (objective response rate)?
  3. How long will patients continue to respond to the therapy untill their disease worsens (progression-free survival)?
  4. Is there a link between overall survival and the tumour expression of PD-L1 (for further information on PD-L1 please read here)? The point of this research (“biomarkers”) is to figure out whether doctors can predict who will respond to this treatment, and who will not. 
  5. What are the side-effects of the therapy and how intensive are they?
The following results were observed:
  1. On average, patients in the group treated with nivolumab had an overall survival (OS) benefit of over 5 months as compared to patients in the group treated with everolimus.
  2. The objective response rate with nivolumab was 25%. In other words, every 4th patient on the trial responded to the new therapy for a period of time. In some cases where treatment was stopped for other reasons than disease progression, the patient’s response appears to have continued.
  3. The median progression-free survival was 4.6 months in the nivolumab group, which was almost the same as in the everolimus group with 4.4 months. The researchers took a closer look at the group of people who responded well to the treatment and had not had disease progression after 6 months of therapy. The analysis from this subgroup of patients yielded a median progression-free survival of 15.6 months.
  4. Nivolumab demonstrated a survival benefit in patients regardless of the extent of PD-L1 expression in their tumours. This indicates that there is no clear biomarker to be used as selection criteria – in other words, it is not clear how to determine which 25% of patients will benefit from the treatment.
  5. Side effects did occur in both groups but seemed to be less severe in the nivolumab arm. The most common treatment-related adverse events among patients who received nivolumab were:

Treatment-related adverse events leading to treatment discontinuation occurred in 8% of the patients treated with nivolumab and in 13% treated with everolimus.

For those that want to read the full paper for the Checkmate 025 study, please see here: http://www.nejm.org/doi/full/10.1056/NEJMoa1510665

CONCLUSION

 

There has been considerable progress in the treatment of renal-cell carcinoma since 2005, when the first targeted therapies (read here) were approved. But we are still looking for further therapies to manage advanced kidney cancerIO therapies are promising, but there are still a lot of questions remaining.

The Checkmate 025 study was the first phase-III study to show clinical benefit of a checkpoint inhibitor (nivolumab) for advanced kidney cancer in the 2nd line setting.
Questions remain to be answered in further studies. For example, there were a number of patients who did not respond to nivolumab at all. Given that 25% of patients receiving nivolumab responded well, how can we predict in advance who will benefit and who will not? Is is safe to stop therapy?

Further research is needed to better understand patient selection criteria including biomarkers, along with possibilities to combine treatment options with new therapies.

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your experience 

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Disclaimer: This is a patient-friendly summary of the results of this clinical trial which has been medically reviewed, but is provided for informational purposes only.
 
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