At ESMO 2020 we reported the five-year follow-up from the SOLO-1 trial. Putting this into context, PARP inhibitors have changed the landscape of ovarian cancer over the last few years so in recurrent ovarian cancer maintenance PARP inhibitors have been shown to significantly delay the time before cancer progression and the time to the next treatment. But unfortunately in the recurrent space so far for the majority of women relapsed disease is not curable.
Therefore, taking PARP inhibitors earlier on in the cancer treatment journey has the potential of improving outcomes further, potential for longer term remissions and perhaps curing more patients so that’s the rationale of bringing PARP inhibitors forward to the first line setting. With the SOLO-1 trial, given the strong signals that were seen throughout the development of PARP inhibitors in patients with BRCA mutations, the SOLO-1 trial was the first trial to look at PARP inhibitors in the first line setting and was in patients in BRCA mutated ovarian cancer.
How was the outcome better in the treatment group compared to the placebo group?
In this updated five-year follow-up of the SOLO-1 trial the benefits of maintenance olaparib continued substantially beyond the end of treatment. So in SOLO-1, just to remind ourselves, this was a randomised trial of maintenance therapy, patients were randomised to receive maintenance olaparib for two years or placebo. The hazard ratio for progression free survival remains significant at 0.33, indicating a 67% reduction in disease progression or death for women in the olaparib arm.
Almost half of patients in the olaparib arm remained progression free five years after randomisation and the median progression free survival on the olaparib arm was 56 months versus 13.8 months in the placebo arm, so an additional 3½ years longer.
Importantly, when we were looking at maintenance therapies and all therapies it’s important to look at the safety profile as well as efficacy. There were no new signals with a long-term follow-up with what was seen previously and, importantly, no new cases of MDS or AML with longer follow-up.
What would the impact of this study be in terms of clinical care and long-term survival for patients?
These results from SOLO-1 represent the longest follow-up for any PARP inhibitor in the newly diagnosed ovarian cancer setting. As I said, over half of women in complete remission, actually, at baseline remained free from relapse five years later after two years of maintenance olaparib. Now we await the final overall survival but it really is encouraging to see longer term remission and also the potential of curing more patients.
These results, importantly, provide further evidence to support the use ofmaintenance olaparib as a standard of care for women with a BRCA mutation in newly diagnosed ovarian cancer.