PIN

The PIN study seeks to address advanced lung cancer, which is a significantly under-researched cause of cancer death.

Background

In 2012, an estimated 14.1 million new cases of cancer occurred worldwide. Lung cancer kills over one million people annually worldwide, non-small cell lung cancer (NSCLC) accounts for around 90% of all lung cancer and kills on average 35,000 in the UK annually (Source: CRUK). NSCLC is one of the leading causes of death worldwide and presents a huge health economic burden. The majority of patients with NSCLC present with locally advanced or metastatic (stage IIIB/IV) disease. Chemotherapy is one of the main treatments for patients with advanced NSCLC but those treated median survival remains modest, at around 9-10 months.

Testing Olaparib following chemotherapy

The purpose of this clinical trial is to find out whether or not giving a drug called Olaparib following chemotherapy will benefit patients with NSCLC who have responded to initial chemotherapy treatment. Olaparib is a type of biological therapy called a PARP inhibitor. It blocks an enzyme that cancer cells need to repair themselves and grow. The researchers think that giving Olaparib after chemotherapy may delay or prevent NSCLC from starting to grow again. This is called maintenance therapy. Olaparib may offer a potentially effective and less toxic cancer treatment compared to currently available chemotherapy regimens. A recent UK trial of maintenance Olaparib (treatment with Olaparib following completion of induction chemotherapy) in patients with ovarian cancer met its primary endpoint of progression-free survival.

Trial aims

The aims of the PIN trial are to find out:

• if Olaparib can help stop or delay non-small cell lung cancer coming back after chemotherapy
• how safe Olaparib is for people with advanced NSCLC
• more about the side effects of Olaparib
• if Olaparib can increase the length of time people with advanced NCSLC live.

Recruitment

114 patients in 23 hospitals across the UK who have responded to chemotherapy will be invited to take part in the trial. Patients will be randomly allocated to receive either Olaparib or an inactive dummy ‘placebo’ tablet by mouth.

Results

Non-small cell lung cancer (NSCLC) is the cause of 4 out of 5 people found to have lung cancer in the UK. Surgery is not a suitable treatment for people with advanced NSCLC because at this stage it has spread to other parts of the body and cannot be fully removed. People with advanced NSCLC are usually treated with anti-cancer drugs including chemotherapy, but most patients will still die less than a year after diagnosis.

The PIN trial was open to patients with advanced NSCLC whose cancer responded well to initial chemotherapy. It is thought that these chemotherapy-responsive tumours are poor at repairing their DNA via the usual methods, so rely on a different method which uses an enzyme called PARP (poly-ADP ribose polymerase). A drug called olaparib has been developed to block the effect of PARP and kill cancer cells which are unable to repair their damaged DNA.  PIN aimed to find out if treatment of patients who had chemotherapy responsive tumours would benefit from treatment with olaparib.

Between August 2014 and November 2017 70 patients entered the PIN trial. 32 patients were assigned to receive an inactive placebo tablet (the control group) and 38 patients to receive active olaparib tablets. This selection was done randomly by a computer and neither the participants nor their doctors knew which treatment they were receiving. The results suggest that it takes longer for the patient’s cancer to re-grow when treated with olaparib compared to placebo. Also, patients receiving olaparib appear to live longer overall. However, the low number of patients in the trial mean we can’t reliably say if these results are likely due to olaparib treatment or due to chance.

These results suggest that advanced NSCLC which responded well to initial chemotherapy have a property which makes them responsive to drugs that block PARP such as olaparib. A number of PARP-blocking drugs have been shown to be successful in the treatment of other cancers in recent years, including ovarian, prostate, breast and pancreatic cancer. Olaparib was well tolerated by patients in the PIN trial, with few unexpected side effects.

Cancer samples donated by participants in the PIN trial will be analysed to see if they have genetic changes which mean they rely on PARP to repair tumour DNA. A future trial with a larger number of patients would investigate if the positive effect of olaparib on suppressing tumour re-growth is genuine and if we can select the patients most likely to benefit from this treatment before they start.