Today we were looking at the long-term safety effects of recurrent ovarian cancer in the maintenance setting and that was conducted via analysing the NOVA trial which is the long-term safety effects of niraparib thus far. The trial is analysing niraparib, it’s a phase III randomised double-blind placebo-controlled study where they looked at patients with recurrent epithelial ovarian cancer, fallopian tube cancer and primary peritoneal cancer who have obtained a complete or rather a partial response with a platinum sensitive chemotherapy. That trial was then broken out into a germcell BRCA mutation versus non-germcell BRCA mutation cohort and that was randomised to a two to one randomisation to either niraparib or a placebo drug.

So we were looking at the safety today to see the effects over time. In the NOVA trial each patient was started off with a fixed dosing of 300mg per day. The patients in the NOVA trial were started off at 300mg fixed dose daily. Dose modifications were made due to adverse events and these dose modifications often took place within the first three months of the treatment. The efficacy of the drug actually didn’t show any difference within the dose modifications. There were dose eliminations or drug eliminations due to adverse events as well at about 14.8% and 3.3% of that was due to thrombocytopenia, so that was the most prevalent. Overall, the main focus of the study showed that niraparib, no matter whether a woman had a germcell line BRCA mutation or a homologous recombination deficiency, that they did have significant progression free survival. This also showed that the quality of life while they took this drug had no difference between whatever cohort they were in, even the placebo, so there was no change or impairment in quality of life. Therefore, especially with a maintenance therapy, it’s crucial to see if patients can tolerate it long-term without significant adverse effects. So this study, or this follow-up of the NOVA trial, was to look3 ½ years out at the tolerance and the safety and the efficacy still of niraparib for those patients.

What were the results?

The NOVA trial found that there was a significant progression free survival over all cohorts, meaning gBRCA mute patients as well as non-gBRCA mute patients. Patients who were in the long term or actually continuing on niraparib, 39% continued over one year and 18.8% continued over two years. The main point with this too, as well, is the safety of these drugs. So these drugs do come with adverse effects, the most common is haematological effects and these were anaemia, neutropenia and thrombocytopenia with thrombocytopenia being the most prevalent. The other cohort of adverse effects were GI effects which were nausea, vomiting and diarrhoea, with nausea being the most prevalent. Then there were other adverse effects that were more prominent which were fatigue, insomnia and hypertension and fatigue was most prevalent out of that group.

The main thing to focus on is that whether you were gBRCA mute or non-gBRCA mute you experienced the same adverse effects, so that didn’t change. Another key point is that the adverse effects happened within the first three months and during those first three months dose reductions usually were made, treatment was individualised for the patient and the adverse effects pretty much resolved and the drug was quite tolerable. So it’s super-important because it’s great to have progression free survival but you want to be able to live your life and have a great quality of life and that’s what this data has reported over the 3½ years looking back into the NOVA trial.

With PARP inhibitors there’s always a risk for MDS and AML. This did happen, however, it happened in the placebo group as well and it was quite rare. There were elevated LFTs as well as adverse effects in grade 3 or above renal issues. These usually happened right away and they also were quite rare. But, at the end of the day, the main concern was the haematological effects with dose reduction. It was quite tolerable and these resolved. Quality of life didn’t change at all between both cohorts and people had the placebo so that was completely stable. So therefore, especially with the 39% of people on niraparib for over a year and 18.8% over two years tolerating it quite well without progression of disease it’s safe to say that this drug and this type of drug in a maintenance therapy is safe for recurrent ovarian cancer patients.

The take home message with this particular PARP inhibitor, niraparib, is that during the first three months patients will experience adverse effects. They will likely be haematological – anaemia, neutropenia, thrombocytopenia, like I said, the GI. There could be nausea, vomiting and diarrhoea and then the other ones that we saw – fatigue, insomnia and hypertension. However, with dose holds, dose modifications and supportive therapies for these adverse effects, after the first three months these seem to resolve with these specialised tweaks in dosing and tweaks in supportive therapies which is huge. Because if we’re showing progression free survival and a tolerability of this drug for a significant amount of time then those first three months it’s super-important for nurses to be assisting with these patients as well as their entire care team to provide the supportive therapies to get through those first three months. Because if you can find the right dosing this could be quite significant, not impact their quality of life and actually give them a longer time without having to deal with their disease.