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Landmark data from the phase 3 SOLO-1 (NCT01844986) and SOLO-2 (NCT01874353) trials collectively established olaparib (Lynparza) as a central component of maintenance therapy for patients with BRCA-mutated ovarian cancer, according to Kevin Elias, MD.^1,2

“Olaparib is still very much one of the treatments of choice for women with somatic or germline [BRCA] mutations who have just finished primary therapy. We have the longest safety and efficacy data for olaparib compared with other PARP inhibitors, and we know that for this subgroup of patients, the benefit is tremendous,” Elias said during an interview with OncLive®. Elias is a gynecologic oncologist and the Lilli and Seth Harris Endowed Chair for Ovarian Cancer Research at the Cleveland Clinic in Ohio.

In the interview, Elias discussed the need for germline and somatic testing at diagnosis, the ongoing investigation of optimal treatment duration, and safety considerations associated with the use of PARP inhibitors.

OncLive: What were the key efficacy findings from the SOLO-1 and SOLO-2 trials?

Elias: The SOLO-1 and SOLO-2 trials were looking at maintenance olaparib therapy. The SOLO studies focused on individuals with germline mutations in the BRCA1 or BRCA2 genes, but in SOLO-1, patients could have somatic mutations in BRCA1 or BRCA2. SOLO-1 was looking at newly diagnosed women who had just finished primary therapy with surgery and a platinum doublet for ovarian cancer and randomized them to either maintenance olaparib therapy, which was [given at a dose of] 300 mg twice daily, or placebo for up to 2 years.

The primary outcome was progression-free survival [PFS], and for women randomized to olaparib, the chances of progression or death were reduced by 70% [compared with placebo]. It was a very positive study.

SOLO-2 was a little bit different [because it looked] at women with recurrent ovarian cancer and only focused on germline mutation carriers. All patients in SOLO-2 had received at least 2 lines of platinum-based chemotherapy and were platinum sensitive in the most recent line. These patients were also randomized to 300 mg of olaparib twice daily or placebo.

Similarly, there was also a strong PFS benefit in that setting, although the magnitude of benefit in the recurrent setting was not quite as great as in the primary setting. In SOLO-2, the median PFS in the olaparib group was 19.1 months vs 5.5 months in the placebo group.

What did the long-term data from SOLO-1 show?

The long-term survival data from SOLO-1 showed that, at 7 years from randomization, the risk of death [was reduced by 45%] for those receiving olaparib vs those in the placebo group. Almost half [45.3%] of patients in the olaparib group were still alive and had not recurred at 7 years, whereas [79.4%] of patients in the placebo group had recurred or died [within that period].

How do these data inform treatment decision-making?

[These data] highlight the importance of understanding underlying germline predisposition in ovarian cancer at initial diagnosis. The earlier we know if someone is a BRCA1 or BRCA2 mutation carrier, either at a germline or somatic level, the sooner we’re able to get them appropriately onto olaparib therapy. We can make a strong recommendation that it alters the treatment trajectory.

What I counsel my patients is that, looking across the studies with olaparib, if they’re a good candidate based on the study criteria, we can cut their risk of relapse or death by more than half by going on [PARP inhibitor] maintenance therapy.

What questions persist regarding olaparib use in ovarian cancer treatment?

We still have questions about olaparib as far as the duration of therapy. In the initial studies, all patients were randomized to 2 years of olaparib therapy. There’s currently a study funded by the NRG that’s randomizing patients to either 2 years or 1 year of maintenance therapy. Two years of therapy was chosen rather empirically, and it could be that patients might benefit from shorter courses, which would be beneficial not only in terms of cost but also [adverse] effects [AEs].

We know these medicines have a risk of myelodysplastic syndrome, and perhaps by exposing patients to shorter durations of therapy, we might reduce one of the most concerning AEs of these drugs.

References

1. 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. 2023;41(3):609-617. doi:10.1200/JCO.22.01549
2. Poveda A, Floquet A, Ledermann JA, et al. Final overall survival (OS) results from SOLO2/ENGOT-ov21: a phase III trial assessing maintenance olaparib in patients (pts) with platinum-sensitive, relapsed ovarian cancer and a BRCA mutation. J Clin Oncol. 2020;38(suppl 15):6002. doi:10.1200/JCO.2020.38.15_suppl.6002