A trial of osimertinib for advanced non small cell lung cancer that has got worse despite treatment (AURA)

Cancer type:

Lung cancer

Non small cell lung cancer

Secondary cancers

Status:

Results

Phase:

Phase 1/2

This trial looked at a drug called osimertinib for non small cell lung cancer. It was for people whose cancer:

had got worse despite having a type of drug called a tyrosine kinase inhibitor
had grown into surrounding tissues or spread elsewhere in the body (advanced cancer)

This trial was open for people to join between 2013 and 2015. The researchers published the results in 2015 and 2018.

More about this trial

Some non small cell lung cancer (NSCLC) cells have changes to certain genes Open a glossary item

. For example, a change in the epidermal growth factor receptor (EGFR) gene. If your lung cancer cells have these receptors it is called EGFR positive Open a glossary item

cancer.

The usual treatment is a type of cancer growth blocker drug called a tyrosine kinase inhibitor (TKI). These drugs block signals that cancer cells use to divide and grow. For example, gefitinib or erlotinib.

But sometimes the cancer develops resistance and treatment stops working. This is due to another gene change called T790M. So, researchers are looking for ways to treat people who have developed resistance or might go on to develop resistance.

In this trial, they looked at a drug called osimertinib (AZD9291). They looked at osimertinib in people:

whose cancer had got worse after a TKI (this included 253 people)
having it as their first TKI treatment (this included 60 people)

This was the first time people had osimertinib. The aims of the trial were to:

look at different doses of osimertinib
find out how well treatment worked
learn more about the side effects

Summary of results

The trial team found that osimertinib worked for most people with advanced NSCLC whose cancer cells had the T790M gene change. And whose cancer had got worse during treatment with a TKI. But it didn’t work well for people whose cancer had got worse during treatment with a TKI but didn’t have the T790M gene change.

They also found that osimertinib worked as a first treatment for people with advanced NSCLC. And whose cancer cells have the EGFR gene change.

They found the side effects weren’t too bad.

Osimertinib in people whose cancer had got worse after a TKI.

253 people took part in total. The trial was in 2 parts. Part 1 was a dose escalation study Open a glossary item

. It looked at different doses of osimertinib in a small number of people. 31 people took part.

222 people joined part 2. It tested these doses in more people. People could join part 2 if the researchers knew whether their cancer had the T790M gene change or not. To do this they tested tissue samples (biopsies Open a glossary item

) that people gave.

The trial team looked at how well treatment worked.

They had information for 239 people. They found:

in 1 person the cancer went away completely (a complete response)
in 122 people the cancer went away a little bit (a partial response)
in 78 people the cancer stayed the same (stable disease)
in 34 people the cancer got worse

Of the 222 people who joined part 2, they looked at who had theT790M gene change. They found:

138 people had the T790M gene change (T790M positive)
62 people didn’t have the T790M gene change (T790M negative)
in 22 people they didn’t know whether they had the gene change or not

The researchers also looked at how well treatment worked. They had the results for 127 people whose cancer cells were T790M positive. They found that in 78 people the cancer went away completely or shrank.

They had the results for 61 people whose cancer cells were T790M negative. They found in 13 people the cancer went away or shrank

They looked at how long people lived before their cancer got worse. This was:

just under 10 months in people who had T790M positive cancer
just under 3 months in people who had T790M negative cancer

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Osimertinib in people having a TKI for as their first treatment.

60 people joined this part of the trial. Of those:

30 had 80 mg of osimertinib once a day, everyday
30 had 160mg of osimertinib once a day, every day

Everyone had treatment for as long as it was working, and the side effects weren’t too bad.

The trial team looked at how well treatment worked. To do this they looked at whose cancer responded to treatment. They found that on average, the treatment worked in just under 8 out of 10 people (77%).

They also looked at how long people lived without their cancer getting worse. This is called progression free survival. On average, this was 20.5 months.

Side effects

The most common side effects of osimertinib were:

diarrhoea
skin rash
feeling sick
loss of appetite

Conclusion

The trial team concluded that osimertinib worked in most people who had a TM790M gene change. But it didn’t work well for people who didn’t have the gene change.

They also found it worked well for people having osimertinib as a first treatment. Another trial looked at having 80mg once a day as this seemed to work better than 160mg a day. We hope to add these results soon.

The trial team have also looked at osimertinib in a trial called AURA 3. We plan to add these results soon.

Where do these results come 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 Open a glossary item

) 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.