Amit Oza, MD, MBBS, FRCPC, Highlights the Benefit of Early Maintenance PARP Inhibitor Use in Ovarian Carcinoma

PARP inhibitors such as rucaparib appear to garner the most benefit in the early maintenance setting in patients with ovarian cancer who have less advanced disease and less heterogeneity, according to Amit Oza, MD, MBBS, FRCPC.

Amit Oza, MD, MBBS, FRCPC, head of the Division of Medical Oncology & Hematology at the Princess Margaret Cancer Centre and co-leader of the Ovarian Cancer Translational Research Imitative at the Ontario Institute for Cancer Research, spoke with CancerNetwork® during the 2022 European Society for Medical Oncology Congress (ESMO) about the optimal time to use maintenance PARP inhibitors such as rucaparib (Rubraca) in ovarian cancer following results from the phase 3 ARIEL4 study (NCT02855944).1

In particular, Oza suggested that early maintenance PARP inhibitors could yield improved survival benefits when the disease may be less heterogenous and advanced vs starting treatment at recurrence when disease burden is greater and more consideration needs to be paid to disease control. He also highlighted how early PARP maintenance allows for a fixed duration approach as opposed to continuous treatment.

Transcript:

In terms of the use of rucaparib, [it] will probably still be driven predominantly in the maintenance setting, which I think is appropriate. Using it early for maintenance and then potentially putting a time limit in terms of how long you give the rucaparib for is a good option to consider. What we're seeing is that when you use it later, you have to be much more mindful of the impact in terms of both disease control, as well as escape from disease control. It's still an option for some patients. Generally, if patients and physicians have the choice, using it earlier is probably going to be better if you look at the totality of evidence.

We have some really good data from [the phase 3] SOLO1 trial [NCT01844986],2 as well as [the phase 3] PAOLA-1 trial [NCT02477644]3 suggesting that there may be an improved survival benefit when you use PARP inhibitors early. If you use it very early when the patient's disease is perhaps less heterogeneous and less advanced, then you may be potentially pushing towards curing some of the patients and using it in a setup for more limited time; that [way], you don't have to continue treatment indefinitely. Whereas if you start [treatment] at the time of recurrence, then it's very hard to stop because patients have a much bigger burden of disease that they're starting off with.

References

  1. Oza AM, Lisyanskaya AS, Fedenko AA, et al. Overall survival results from ARIEL4: a phase III study assessing rucaparib vs chemotherapy in patients with advanced, relapsed ovarian carcinoma and a deleterious BRCA1/2 mutation. Ann Oncol. 2022;33(suppl 7):S235-S282. doi:10.1016/annonc/annonc1054
  2. DiSilvestro P, Banerjee S, Colombo N, et al. Overall survival with maintenance olaparib at a 7-year follow-up in patients with newly diagnosed advanced ovarian cancer and a BRCA mutation: The SOLO1/GOG 3004 Trial. J Clin Oncol. Published online September 9, 2022. doi:10.1200/JCO.22.01549
  3. González-Martín A, Desauw C, Heitz F, et al. Maintenance olaparib plus bevacizumab in patients with newly diagnosed advanced high-grade ovarian cancer: Main analysis of second progression-free survival in the phase III PAOLA-1/ENGOT-ov25 trial. Eur J Cancer. 2022;174:221-231. doi:10.1016/j.ejca.2022.07.022