Maintenance olaparib prolongs survival in ovarian cancer

In women with newly diagnosed, advanced* ovarian cancer and a BRCA mutation**, the progression-free survival (PFS) benefit with maintenance olaparib was sustained beyond end of treatment, according to the 5-year follow-up results of the SOLO1 trial presented at SGO 2021.

“[The] sustained PFS benefit was observed following 2 years of treatment with maintenance olaparib, which is the only PARP*** inhibitor for which efficacy has been demonstrated beyond completion of therapy,” noted Dr William Bradley from Froedtert and the Medical College of Wisconsin, Milwaukee, Wisconsin, US, in his presentation.

At 5 years, nearly half of the participants on olaparib were free from disease progression (48 percent), which was more than twice the fraction of placebo recipients who were progression-free (21 percent).

The findings provide promise for a disease that has a 5-year survival rate of up to 50 percent and a high risk of relapse. [J Clin Oncol 2019;37:2317-2328; Ann Oncol 2013;24:vi24-vi32] “[As such,] treatment goals … include delay of recurrence, prolonged survival, and, for some patients, increased chance of cure,” noted Bradley.

The study comprised women with advanced ovarian cancer who have had a complete response (CR) or partial response following first-line platinum-based chemotherapy. Participants were randomized 2:1 to receive olaparib 300 mg BID or placebo for up to 2 years or until disease progression. [SGO 2021, abstract 10520]

PFS was longer with olaparib vs placebo (median, 56.0 vs 13.8 months; hazard ratio [HR], 0.33, 95 percent confidence interval [CI], 0.25–0.43). Median treatment duration was 24.6 months for olaparib and 13.9 months for placebo.

The PFS benefit was also consistent across higher- (median, 40.6 vs 11.1 months; HR, 0.35, 95 percent CI, 0.25–0.49) and lower-risk patient subgroups (median, not reached vs 21.9 months; HR, 0.38, 95 percent CI, 0.25–0.59).

Olaparib also outdid placebo in terms of time to second progression or death (HRs, 0.46 and 0.48 for the overall population and among women in CR at baseline, respectively) and time to second subsequent therapy (HRs, 0.46 and 0.50, respectively).

Compared with placebo use, olaparib use led to higher rates of grade >3 adverse events (AEs; 40 percent vs 19 percent) and serious AEs (21 percent vs 13 percent), as well as AEs leading to dose interruption (52 percent vs 17 percent), dose reduction (29 percent vs 3 percent), and treatment discontinuation (12 percent vs 3 percent).

Nonetheless, these safety findings were consistent with the initially reported safety profile, with no new safety signals observed, and no new cases of myelodysplastic syndrome or acute myeloid leukaemia (MDS/AML) reported at 5 years. “[The] incidence of MDS/AML remained <1.5 percent,” noted Bradley.

“[A]fter the longest duration of follow-up, to our knowledge, for any PARP inhibitor in the newly diagnosed advanced ovarian cancer setting … [our findings] further support the use of maintenance olaparib as a standard of care [in this patient setting], and suggest the possibility of long-term remission or even cure for some patients,” concluded Bradley.