It’s my privilege to be the Track Chair of the gynaecological cancers track this year at ESMO and I’m an ESMO executive board member. So in the next few minutes we will cover the standard of care and progress so far in PARP inhibitors for ovarian cancer. The disclosure slide is here.
Just to put this into context, ovarian cancer is among one of the most common cancers affecting women and the travesty is it has one of the highest mortality rates. So it’s the eighth commonest cancer affecting women and what you can see here, that although there are many more women suffering from breast cancer, when you look at the incidence compared to the mortality there are higher rates of death from ovarian cancer compared to the other more common women’s cancers.
But there has been progress in advanced ovarian cancer treatments and in particular significant advances with targeted therapy, which is what I’m going to focus on today. So bevacizumab and PARP inhibitors do provide new hope for ovarian cancer patients and in order to illustrate this today for you I thought it would be helpful to look at the EMA approval since the first targeted therapy in ovarian cancer, so going back over a seven year period from 2011 to 2018. The first targeted therapy to gain approval was bevacizumab and this drug blocks a molecule called VEGF which attacks blood vessels which cancers need to thrive. The indication in 2011 was in the front line treatment for women with advanced ovarian cancer in combination with chemotherapy and then also taken as a maintenance therapy afterwards by itself. Following this, shortly after, in the next few years bevacizumab gained indications and approvals for the treatment of women with relapsed or recurrent disease.
The next real wave of breakthroughs of approvals come with PARP inhibitors and, as you will see here, there are three PARP inhibitors, olaparib, niraparib and rucaparib, which have EMA approval. The first PARP inhibitor to be approved was olaparib capsules and that was back in 2014 and it really changed the landscape of treatment. This is for women with BRCA mutated ovarian cancer in the relapsed setting as a maintenance therapy. As you will see, so far all the indications for PARP inhibitors are in the relapsed setting, so not in the front line. Back in 2014 it really fuelled and highlighted the importance which we currently still have very much so at the forefront – the importance and need for access to BRCA mutation testing for women with ovarian cancer.
Niraparib gained approval in 2017 and the difference here of the new breakthrough was access of PARP inhibitors for women regardless of BRCA mutation status and then a year later that was the indication for olaparib as well. Finally rucaparib has approval as treatment for women with BRCA mutated ovarian cancer as opposed to maintenance therapy.
As I’ve shown you, the standard of care has really changed, with the PARP inhibitors changing the landscape. PARP inhibitors are effective and approved in women with recurrent ovarian cancer that has returned more than six months after completing the backbone of chemotherapy which is platinum-based chemotherapy for women with ovarian cancer. So how do these work, quickly? PARP inhibitors work by blocking an enzyme called PARP which is heavily involved in the repair of DNA in cancer cells. So with these drugs DNA in cancer cells can’t be repaired and that leads to cancer cell death. We know that these drugs are most effective in women with known problems with DNA repair, so BRCA gene mutations, and Angelina Jolie raised the profile of the relevance of BRCA mutations as she is a BRCA1 carrier and unfortunately her mother died at the age of 56 with ovarian cancer. So one in six of the most common ovarian cancer types, that’s high grade serous ovarian cancer, one in six women have a BRCA mutation so this is highly relevant.
In relapse PARP inhibitors significantly delay the time until cancer returns or worsens and the time to the next treatment which is often chemotherapy. So I’ve mentioned three PARP inhibitors that have approval and in BRCA mutated patients the overall results are very similar for all the PARP inhibitors. There is a significant and substantial reduction in the risk of progression by between 70-75% and that is very meaningful for women with ovarian cancer. To put it into context with regards to time, if we look to median, that means average, progression free survival, for example with olaparib, for women that are in the placebo arm in relapsed ovarian cancer that didn’t get olaparib the median time was around 5 months and for women with olaparib that was extended, the time before progression, to over 19 months.
So PARP inhibitors are only available, as I’ve discussed, for women whose cancer has come back. So what about treatment for newly diagnosed ovarian cancer, that includes women with BRCA mutations? It remains surgery and platinum based chemotherapy, so carboplatin and paclitaxel, as the standard of care and in many countries bevacizumab is also part of standard of care. But despite these treatments for the majority of women the time before progression after standard of care is between 10-20 months. What we do know is 70% of women relapse within three years of first line treatment. The five year survival rate for advanced ovarian cancer for stage 3 patients is only 20% and for those with stage 4 disease that drops to 5%.
I hope I have shown you that there is an urgent need to improve treatments for women with advanced ovarian cancer and with that I’ll had over to our next speaker.