Spacing out treatment for kidney cancer over a longer period produces fewer side effects without diminishing results.
A new study, run through the Clinical Trials Research Unit at the University, examined the implications of administering drugs over a 48-week period, instead of the standard 12 weeks.
As a result the proportion of patients experiencing serious side effects during treatment dropped by 20%.
The findings have been presented to the European Society for Medical Oncology (ESMO) by the Chief Investigator for the study Dr Naveen Vasudev, from the Leeds Institute of Medical Research at St James’s and Leeds Cancer Centre, and Consultant Medical Oncologist at Leeds Teaching Hospitals NHS Trust.
Dr Vasudev said: “This positive phase II study provides very encouraging results and suggests that it may be possible to improve how well tolerated immunotherapy drugs are, without compromising how well they work, in patients with advanced kidney cancer.”
Some 13,000 people are diagnosed with kidney cancer every year in the UK, making it the seventh most common UK cancer.
Immunotherapy is a type of treatment which works by stimulating the body’s own immune system to fight against cancer cells. Clinical trials have shown that giving two immunotherapy drugs together – nivolumab and ipilimumab – is an effective initial treatment for many patients with advanced kidney cancer.
However, using both drugs together is known to cause more side effects than using the drugs by themselves. These side effects can sometimes be unpleasant and/or serious and may even mean that treatment needs to be stopped early.
The best timing of giving these drugs is not known. The PRISM* trial aimed to shed light on this question, exploring whether giving one of the drugs (ipilimumab) less often, but over a longer time period (i.e. receiving the same amount of drug in total), would result in fewer side effects, while still working as well as when given in the standard way.
The study showed a significant reduction in the number of patients experiencing serious side-effects by giving ipilimumab every 12-weeks for four doses (modified schedule) instead of the current standard way, which is to give it every three weeks for four doses (standard schedule).
We still have a lot to learn about how to use immunotherapy drugs most effectively, whilst doing the least harm
Fewer patients also had to stop treatment due to side-effects when the ipilimumab was given every 12 weeks. Whilst leaving longer between each dose of treatment can lead to concerns about loss of activity, the results from the trial reassuringly did not suggest any obvious differences in how well the treatment worked when giving ipilimumab less often.
Patients with untreated, advanced kidney cancer were invited to take part in the study, which involved 15 hospitals across the UK. 195 patients took part, with two thirds of participants randomly allocated to the modified ipilimumab schedule (every 12 weeks).
The study was designed in such a way that the two treatment schedules could be formally compared with each other in terms of treatment toxicity/side effects. The study showed a significant reduction in serious side effects with the modified schedule (33%) compared to the standard schedule (53%).
Overall, 23% of patients receiving the modified schedule stopped therapy due to treatment-related side-effects, versus 39% in patients receiving the standard schedule.
How long patients lived and the amount of tumour shrinkage looked similar in both groups, but due to the size of the study, the trial could not definitively prove this.
Comparing drug schedules
Dr Vasudev added: “Whilst three-weekly ipilimumab dosing currently remains the standard approach, the data should provide reassurance to doctors and patients if doses of ipilimumab need to be delayed for any reason.
“We still have a lot to learn about how to use immunotherapy drugs most effectively, whilst doing the least harm.”
The trial is also of wider importance as it is the first of its kind to formally compare the safety of different ipilimumab schedules. Its findings are likely to be of interest to those treating other cancer types in which the nivolumab plus ipilimumab combination is used, such as melanoma (skin cancer).
Dr Fiona Collinson from the Leeds Clinical Trials Research Unit, who was Scientific Lead for the trial, said: “There have been exciting improvements in the drugs available to treat advanced kidney cancer over recent years.
“The PRISM trial – investigating a less intense ipilimumab regime, along with the STAR trial investigating planned treatment breaks in tyrosine kinase inhibitor treatment – are paving the way in working out the best way of giving these treatment options.
“We know we have drugs that can make patients live longer. A challenge is finding out how we can make patients live better during this time.”
*PRISM trial: nivolumab in combination with alternatively scheduled ipilimumab in first-line treatment of patients with advanced renal cell carcinoma.
The findings were presented by the Chief Investigator for the study Dr Naveen Vasudev at the Annual Conference of the European Society for Medical Oncology (ESMO) held in Paris 16–21 September 2021.
The ESMO Annual Conference is one of the two main annual world cancer meetings in this field, typically attracting an audience of 20,000-40,000.
This trial was funded by Bristol-Myers Squibb (BMS) with support from the Yorkshire Cancer Research (YCR) Early Phase Centre based at the University of Leeds.
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