Comment: PARP inhibitor olaparib plus bevacizumab in women with ovarian cancer

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Published: 28 Sep 2019
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Dr Susana Banerjee - The Royal Marsden NHS Foundation Trust, London, UK

Dr Susana Banerjee comments on data, during a press conference at the 2019 ESMO congress, from the PAOLA-1/ENGOT-ov25 trial.

This was a phase III randomised trial which looked at the maintenance combined targeted therapy of PARP inhibitor olaparib added to bevacizumab, in patients with and without a BRCA mutation.

Watch the press conference here

Watch Prof Isabelle Ray Coquard's interview with ecancer here

Read more about the study here

Thank you. It’s my role to try and put this into context. So, just to remind ourselves that ovarian cancer is the eighth commonest cancer in the world with 295,000 women being diagnosed and over 185 deaths. The issue with ovarian cancer is that the majority of women relapse and that’s the real issue. So 70% within three years and the five year survival for stage 3 is 20% and for stage 4 disease 5%.

PARP inhibitors have revolutionised the treatment landscape of ovarian cancer. PARP inhibitors, so olaparib, which we’ve heard about, niraparib and rucaparib, are approved in recurrent ovarian cancer and have been shown to improve the progression free survival. But if we’re really going to have a chance to increase overall survival and hopefully more women cured we need to bring these treatments into the first line setting. Here in this Presidential Symposium last year at ESMO and in this press release you heard me talk about the results of the SOLO-1 trial. The SOLO-1 trial has changed the landscape of first line treatment, this was presented at ESMO’s Presidential Session last year and published in The New England Journal of Medicine. What that showed was that for women with BRCA mutations, following chemotherapy and having had a response to then have maintenance olaparib for a two year period, what we saw there was that women, compared to the placebo group which was standard of care, that they had a hazard ratio of 0.3 which comes later to a median progression free survival of over three years, compared to the placebo group of 13 months.

So what does PAOLA-1, Isabelle Ray-Coquard’s study, add and what else are we going to hear during this congress? Well, there are three studies in the first line setting presented at today’s Presidential Session. You’ve already heard the results of PAOLA-1; there’s also the PRIMA/ENGOT-ov26 study and also the VELIA study.

Now, the key question for me, as a clinician and a trialist, is how can we improve on the results and standard of care that we’ve had so far? The main questions are can more women benefit from a PARP inhibitor in the first line setting beyond those women with BRCA mutations and we’ve eloquently seen from Isabelle Ray-Coquard that that is possible. So the next main question, really, is if patients can benefit beyond patients with BRCA mutation how can we best select which patients are going to benefit for the longest time? That brings in the concept of HRD deficiency. The other question is about can we improve by combining treatments so, for example, you heard in PAOLA-1 olaparib combined with bevacizumab.

Taking those two main points, the PRIMA-1 study was looking at niraparib as maintenance treatment. So just like what I said in SOLO-1 – no combination, maintenance treatment alone but with a PARP inhibitor, niraparib, beyond women with BRCA mutations. The key point there is, just like what we’ve seen in PAOLA-1, that we’ve got confirmation that more women can benefit from PARP inhibitors. So we also see that with the VELIA study which is a US-led study which is looking at combining a PARP inhibitor, veliparib, with chemotherapy at the same time together and then having maintenance veliparib. You’ll hear the results later on today but essentially that shows that chemotherapy with veliparib and veliparib maintenance therapy is better than no PARP inhibitor alone and that’s been shown in patients with and without BRCA mutations.

So the real questions are we know now, for the end of today, the Presidential Sessions, that we can use PARP inhibitors in the first line setting beyond women with BRCA mutations. The key question, really, is what about patients that don’t have HRD deficiency? We do know that patients with BRCA mutations and that are HRD positive have the greatest benefit from either a PARP inhibitor alone or, indeed, in combination with bevacizumab.