Trial description
Veliparib is a poly adenosine diphosphate-ribose polymerase Inhibitor (PARP inhibitor). It works by blocking a protein called PARP. Blocking this protein means the cancer cell can no longer repair damage in its DNA and so when this damage occurs the cancer cell cannot repair it and subsequently dies. PARP inhibitors are taken by mouth.
1140 patients participated in this study. All had previously untreated stage III or IV high-grade serous ovarian cancer. Some had surgery first while others had surgery after 3 rounds of chemotherapy. This was a placebo-controlled trial, meaning that some participants were given tablets to take that didn’t contain any of the active drug. This is done to try and prevent both researchers and participants knowing which participants are and are not on the active medication to prevent them from being influenced when analysing the results.
Participants were randomly assigned to one of three groups. The first group received standard chemotherapy with placebo during chemotherapy and as maintenance. The second group received standard chemotherapy with veliparib and placebo as maintenance. The third group received standard chemotherapy with veliparib and veliparib as maintenance.
All participants had testing to identify if they had a BRCA mutation which was inheritable (called a germline BRCA mutation) and had their tumour tested to see if it had a BRCA mutation within it – this is called a somatic BRCA mutation and is not inheritable. Participants also had testing for ‘homologous recombinant deficiency’ or HRD – this is a test to see if the cancer cell has defects in the ways it tries to repair DNA damage. BRCA mutations cause similar errors in the cancer cells ability to repair DNA damage. It is known that cancer cells with BRCA mutations and HRD are more susceptible to being killed by chemotherapy and by PARP inhibitors. For more information about PARP inhibitors in ovarian cancer please search for ‘PARP inhibitors’ in the search bar on thisisGO.ie.
Outcome
The patients who took veliparib with their chemotherapy and as maintenance had a significant longer progression free survival (PFS) than those who didn’t take any veliparib at all. PFS is a measure of time from when the patient joined the study until the cancer progressed or got worse.
Patients who had a BRCA mutation had the greatest benefit with an average PFS of 34.7 months compared with an average PFS of 22.0 months in the patients who had chemotherapy only. This means that patients with a BRCA mutation who took veliparib during chemotherapy and as maintenance had more than a year more time without the cancer progressing than those who took chemotherapy only. Patients with HRD (which includes the BRCA patients as well as those with other errors in DNA repair mechanisms) also had a benefit but less than those with the BRCA mutations.
Finally, all participants including those who didn’t have a BRCA mutation or HRD had a benefit with an average PFS of 23.5 months compared with 17.3 months in those who had chemotherapy alone, meaning all people in the study who took veliparib had 6.2 months more time until the cancer progressed than those who had chemotherapy alone.
People who took veliparib had more nausea and more fatigue and also were more likely to have low haemoglobin and low platelets than those who had chemotherapy alone.
Conclusion
Adding Veliparib to the initial treatment with carboplatin and paclitaxel and using it as a maintenance resulted in a significant difference in progression free survival. This difference was greatest in people who had a BRCA mutation.
