Maintenance Olaparib Improves PFS For BRCA1/2 Relapsed Ovarian Cancer

Maintenance olaparib achieved longer progression-free survival than placebo for recurrent high-grade serous ovarian cancer or high-grade endometrioid cancer in patients with a BRCA1/2 mutation

medwireNews: Preliminary results from the SOLO2/ENGOT-Ov 21 trial suggest a role for maintenance olaparib in patients with BRCA1/2-mutated, relapsed, high-grade serous ovarian cancer or high-grade endometrioid cancer that has responded to second-line or later platinum-based chemotherapy.

“The improvement in progression-free survival [PFS] seen using the olaparib tablet formulation in this disease setting is compelling because patients were able to maintain a good quality of life while experiencing a delay in disease progression and, therefore, a delay until the symptoms associated with subsequent chemotherapy treatments”, say Eric Pujade-Lauraine, from Université Paris Descartes in France, and co-investigators.

The researchers add in The Lancet Oncology that the trial used a new formulation of olaparib that reduced the daily pill burden from 16 capsules to four tablets, while maintaining the same exposure, and thus “providing patients with a simpler, more convenient treatment regimen.”

The primary endpoint of investigator-assessed PFS was significantly longer for the 196 patients randomly assigned to receive olaparib 300 mg twice daily than for the 99 patients who were given placebo, at 19.1 versus 5.5 months and a hazard ratio of 0.30.

Olaparib was associated with a higher rate of PFS than placebo after 12 months (65 vs 21%) and 24 months (43 vs 15%), and PFS was significantly longer with olaparib versus placebo in the subgroup of patients who had previously been treated with bevacizumab (17.0 vs 5.1 months, HR=0.14).

Although yet to mature, data suggest that overall survival may be comparable between the olaparib and placebo treatment groups, at 23% and 27%, respectively, the authors observe.

However, other secondary endpoints were in favour of olaparib at interim analysis, such as median time to first subsequent therapy (27.9 vs 7.1 months), median time to second progression (unreached vs 18.4 months), and median time to second subsequent treatment (unreached vs 18.2 months).

The team also reports quality of life data for the study, finding no difference between the treatment arms for the Trial Outcome Index of the Functional Assessment of Cancer Therapy– Ovarian Cancer questionnaire from baseline to 12 months.

The majority of adverse events were grade 1–2, affecting 62% and 77% of the olaparib and placebo groups, respectively. These were most commonly nausea, fatigue or asthenia, abdominal pain, vomiting and diarrhoea. Both arms had a low rate of grade 3–5 events; anaemia was the most common grade 3 event with olaparib, affecting 18% versus 2% of controls, and blood transfusion was required in a corresponding 18% and 1%, respectively.

One patient in the olaparib arm had a treatment-related fatal adverse event – acute myeloid leukaemia – but the incidence of secondary malignancies was comparable in the olaparib and placebo groups, at 3% and 5%.

Discussing the findings in an accompanying comment, Michael Bookman (US Oncology Research, Tucson, Arizona, USA) and Henry Kitchener (University of Manchester, UK) say that further research is required to determine the use of olaparib and other poly(ADP-ribose) polymerase (PARP) inhibitors in patients without BRCA1/2 mutations.

Ongoing research, including the GOG3005, SOLO1 and PRIMA trials, will also address the role of PARP inhibitors as first-line treatment given alongside chemotherapy or as a front-line maintenance therapy, they say.

“Combinations of PARP inhibitors with other agents have become a priority for innovative research, to optimise the potential benefit of immunotherapeutics, anti-angiogenic agents or drugs targeting DNA damage response pathways”, the commentators write.

“These trials will hopefully extend the benefit of PARP inhibitors to patients with less favourable molecular and clinical profiles. In the meantime, PARP inhibitors represent an important class of drugs for use in recurrent ovarian cancer.”


Pujade-Lauraine E, Ledermann JA, Selle F, et al. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol; Advance online publication 25 July 2017

Bookman MA, Kitchener HC. To promote maintenance or treatment, is that the question? Lancet Oncol; Advance online publication 25 July 2017

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