A trial looking at durvalumab with or without tremelimumab for non small cell lung cancer that has spread (ARCTIC)

The trial team found that the combination of durvalumab and tremelimumab didn’t improve treatment outcome for advanced NSCLC any more than the usual treatment. 

There was a slight increase in how long people who had durvalumab on its own lived. But the difference isn’t big enough for the research team to say for sure that it’s because of durvalumab treatment.

Trial design
This was a phase 3 trial. It took place worldwide. 

The team had hoped to find about 1,560 people to join. But it was difficult to find enough people. This was because newer treatments were approved for NSCLC at the start of the trial. 

595 people in total took part. 

The team looked at a sample of cancer tissue (biopsy)  from everyone in the trial. This was a sample that people gave when their cancer was first diagnosed. 
 
The team tested the sample for a protein called PD-L1. Cancer that has large amounts of PD-L1 is PD-L1 positive. Cancer that has small amounts of PD-L1 is PD-L1 negative. 

This trial had 2 separate parts. People who had PD-L1 positive cancer joined study A. People who had PD-L1 negative cancer joined study B.

People had one of the following treatments:

• durvalumab
• tremelimumab
• durvalumab and tremelimumab
• usual treatment 

The usual treatment options for study A and study B included 1 of the following: 

• a chemotherapy drug called gemcitabine
• a chemotherapy drug called vinorelbine
• a targeted drug called erlotinib

The doctor recommended the best suitable standard treatment option. 

Treatment groups
Study A was for people whose cancer was PD-L1 positive. 126 people joined study A. There were 2 treatment groups. People were put into a treatment group at random:

• 62 people who were PD-L1 positive had durvalumab
• 64 people who were PD-L1 positive had usual treatment

Study B was for people whose cancer was PD-L1 negative. 469 people joined study B. There were 4 treatment groups. People were put into a treatment group at random:

• 174 people who were PD-L1 negative had durvalumab and tremelimumab
• 118 people who were PD-L1 negative had usual treatment
• 117 people who were PD-L1 negative had durvalumab
• 60 people who were PD-L1 negative had tremelimumab

Diagram 1

Results for study A
The trial team looked at how well treatment worked. To do this they looked at how long before the cancer started to grow again after starting treatment. They found this was about:

• 3.8 months for those who had durvalumab
• 2.2 months for those who had usual treatment

They also looked at how long people lived after starting treatment. They found it was:

• 11.7 months for those who had durvalumab
• 6.8 months for those who had usual treatment 

Results for study B
The team looked at how well treatment worked. They were mainly interested in the combination of durvalumab and tremelimumab compared with usual treatment. 

The team looked at how long before the cancer started to grow again after starting treatment. They found it was:

• 3.5 months for those who had durvalumab and tremelimumab or 
• usual treatment
• 3.1 months for those who had durvalumab alone
• 2.1 months for those who had tremelimumab alone 

So they didn’t find a difference between people who had the combination of durvalumab and tremelimumab and those who had usual treatment. 

The team also looked at how long people lived after starting treatment. They found this was:

• 11.5 months for those who had durvalumab and tremelimumab
• 8.7 months for those who had usual treatment
• 10 months for those who had durvalumab
• 6.9 months for those who had tremelimumab

Although these numbers look different. The difference isn’t big enough for the research team to say for sure that it’s because of the different treatments. It could be due to chance.

Side effects
Most people who took part in this trial had at least 1 side effect. Most were mild or didn’t last long. More people in the usual treatment group had side effects that were severe. 

Study A
The trial team looked at all the side effects. We have included those that they think were related to treatment. 

The severe side effects of usual care were:

• a drop in white blood cells causing an increased risk of infection  
• a drop in red blood cells causing an increased risk of breathlessness and tiredness (anaemia )
• a high temperature (febrile neutropenia) and low levels of white blood cells

The most common side effects of usual care were:

• a drop in red blood cells (anaemia)
• loss of appetite 

The most common side effects of durvalumab included:

• loss of appetite
• tiredness (fatigue) 

Study B
The trial team looked at all the side effects. We have included those that they think were related to treatment. 
People who had durvalumab on its own had more side effects that were mild.

The side effects of usual care were similar to those found in study A.

The most common severe side effects of:

• durvalumab and tremelimumab were diarrhoea and inflammation of the lung tissue (pneumonitis )
• durvalumab alone were fatigue and shortness of breath
• tremelimumab alone was diarrhoea

In study B, one person died during treatment with durvalumab. And one person died during treatment with tremelimumab.

Conclusion
Study A was for people who had PD-L1 positive NSCLC. There was a slight increase in how long people who had durvalumab only lived compared with usual treatment. The difference between the groups wasn’t big enough to say for sure. 

Study B was for people with PD-L1 negative NSCLC. In study B, the team concluded that the combination of durvalumab and tremelimumab was no more effective than usual treatment. It didn’t increase the length of time before the cancer started to grow again or how long people lived compared with usual treatment. 

Even so, all trial results help doctors and researchers understand more about different cancers and the best way to treat them. 

There are other trials looking at durvalumab on its own for people with NSCLC. And there are also trials looking at durvalumab in combination with tremelimumab.   

Where this information comes from    
We have based this summary on information from the research team. The information they sent us has been reviewed by independent specialists (peer reviewed ) and published in a medical journal. The figures we quote above were provided by the trial team who did the research. We have not analysed the data ourselves.