First-line treatment of advanced kidney cancer look promising

Preliminary results of new combination immunotherapy, for first-line treatment of advanced kidney cancer, look promising.

We are extremely pleased that NICE has recommended nivolumab as a 2^nd line treatment for advanced kidney cancer, as this provides patients with more treatment options and benefits.  However, just prior to this positive decision by NICE, further developments within the field of renal cancer immunotherapy were released:  providing preliminary results that detailed how a combination of two monoclonal antibodies (nivolumab and ipilimumab) used together as a first-line treatment for advanced kidney cancer, looked even more promising.
Nivolumab and ipilimumab combination therapy
An abstract detailing preliminary clinical trial results for a combination of two immunotherapy drugs (nivolumab and ipilimumab) has been presented at the European Society for Medical Oncology (ESMO) conference. The phase 1 trial (checkmate 016) has shown that 40% of people responded positively to the nivolumab/ipilimumab combination as their tumours shrank significantly ¹. It is important to note that standard treatment only achieves this in 5% of cases. This information is hugely encouraging but we must be patient while the drug combination goes through the clinical trial process. This drug combination is already in NHS use for melanoma treatment.
Currently there is a phase 3 trial (checkmate 214) investigating the use of the drug combination in advanced renal cancer, which is ongoing although it has finished recruiting. A phase 3 trial recruits more people than a phase 1 trial and gives even more detail on the effects of the drug. The trial is comparing the immunotherapy combination to sunitinib (current standard treatment, tyrosine kinase inhibitor) in previously untreated patients (first-line treatment).  On the checkmate 214 trial the combination therapy is given intravenously every three weeks for four doses, then nivolumab is given alone every two weeks on an ongoing basis. In comparison, sunitinib is taken by mouth daily for four weeks, then two weeks off on a continuous basis.
The fact that the nivolumab/ipilimumab combination is being trialled as a 1^st line treatment is an advancement for immunotherapy in renal cancer. Currently, nivolumab has been recommended by NICE as a monotherapy, but as a second-line treatment based on the evidence from the checkmate 025 trial where it is compared to everolimus treatment.
How do immunotherapy drugs work?
Nivolumab (Opdivo) acts in a different way to other current treatments for kidney cancer which either aim to kill tumour cells or stop tumour cell growth. Nivolumab is an anti-PD-1 (programmed death-1) monoclonal antibody which acts by blocking the receptor PD-1 on T-cells (cells of the immune system), which reinvigorates the T-cells and allows them to attack the cancer cells. T-cells are often inactivated by a substance that cancer cells produce, which activates the PD-1 receptor on T-cells. Activating the PD-1 receptor causes the T-cell to become inactive so it doesn’t do its job and attack cancer cells. Nivolumab acts as an immunomodulator and stops the PD-1 receptor from being activated which in turn boosts the body’s own ability to attack cancer cells.
Ipilimumab (Yervoy) is also a monoclonal antibody which acts by activating the immune system so it can attack cancer cells. It works in a similar way to nivolumab but targets CTLA-4 receptors on T-cells, which are also involved in an inhibitory mechanism of the immune system.
Targeting both receptors together appears to have an increased effect on reducing the inhibition of the immune system.
What are the advantages and disadvantages of immunotherapy drugs?
Offering more choice and the latest scientific developments
Ultimately the development of a new class of drugs is good news as some drugs work for some people but not for others. A wider range of tools to fight kidney cancer is of huge benefit. Immunotherapy is a subtle and clever way of working with the body to boost the job that immune cells should be doing: destroying cells that are malfunctioning. Cancer cells are equally clever and produce substances such as PD-1, which reduce the immune cells activity, allowing themselves to go undetected. So we must aim to be equally sophisticated by fighting cancer without destroying healthy cells and without depleting energy recovering from side-effects, which is what often occurs with many of the standard treatments for kidney cancer.
Side-effects
Reports show that nivolumab and ipilimumab have mild side-effects compared to other cancer treatments but we must highlight that immunotherapies can have side-effects. The most common adverse effects are immune related, such as: inflammation of the bowel (diarrhoea and colitis), skin (skin rash/pruritus), nervous system (neuropathy), thyroid (hyper and hypothyroidism), kidney (nephritis), heart (myocarditis), pancreas (pancreatitis), or lungs (pneumonitis). Hepatotoxicity can also occur (raised liver enzymes). Liver enzymes and thyroid hormone levels are recorded at baseline and before administration of the drugs to monitor these effects ². This list is not compiled to deter you from using immunotherapies but it is important that you are aware that you may not be able to tolerate these drugs or that you may have your dose delayed in order to get side-effects under control. Corticosteroids are most commonly used in these cases, which are also not without side-effects. Just as different drugs suit different people, the same applies with whether or not you will have side-effects. You may hopefully be with the majority that have very few side-effects at all.
Convenience
Another consideration is the administration of monoclonal antibodies. The drugs are delivered using IV access which involves you being at a hospital or local cancer centre and the drug being pumped into your body over about 90 minutes, via a cannula. Many people are more than willing to do this for the opportunity of receiving the treatment, but it is not quite as convenient as daily oral pills, which is how other targeted therapies (tyrosine kinase inhibitors such as sunitinib) are generally administered.
The future of immunotherapy in advanced renal cancer.
We eagerly await the publication of this immunotherapy combination research and positive appraisals by NICE.  KCUK believe that the use of immunotherapy, although still in its infancy, is looking very promising for the future. There will be new immunotherapy drugs and combinations that can be explored. We are extremely pleased that nivolumab has been approved by NICE for use in the NHS as a second-line treatment but we are also excited about the possibilities of a first-line nivolumab/ipilimumab combination therapy for the future.
We would love to hear any feedback from people that are currently involved in immunotherapy trials and have had first-hand experience of these therapies. Please get in touch with us if you would like to share your experience with others. CLICK HERE TO CONTACT US

1. Details on Checkmate 016 phase 1 trial. Retrieved October 2016: http://news.bms.com/press-release/bristolmyers/updated-results-presented-opdivo-nivolumab-and-yervoy-ipilimumab-combinat
2. Yervoy annex I: summary of product characteristics. Retrieved October 2016. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002213/WC500109299.pdf