SOLO-1 Data Support Use of Olaparib Maintenance to Achieve Long-Term Remission in BRCA+ Advanced Ovarian Cancer

Paul A. DiSilvestro, MD

Seven-year follow-up data from the phase 3 SOLO-1/GOG-3004 trial (NCT01844986) provide further confirmation of the long-term survival benefit achieved with maintenance treatment with olaparib (Lynparza) vs placebo in patients with newly diagnosed, advanced ovarian cancer harboring a BRCA mutation, according to Paul A. DiSilvestro, MD.

Data from the trial, presented at the 2022 ESMO Congress, showed that the median overall survival (OS) was not yet reached in patients treated with olaparib (n = 260) vs 75.2 months in those who received placebo (n = 131; HR, 0.55; 95% CI, 0.40-0.76; P = .0004).¹ The 60-month OS rate in the experimental arm was 73.1% compared with 63.4% in the control arm; at 84 months, these rates were 67.0% vs 46.5%, respectively.

“[It was] exciting to see that separation of the curves [that we saw in the progression-free survival [PFS] analysis] persist; [this indicates that] there was an enduring benefit beyond the 2-year treatment cap,” said DiSilvestro, who is director of the Program in Women’s Oncology for Women & Infants Hospital of Rhode Island and Care New England Health System. “We treated people for 2 years, but 5 years later we're still seeing that separation. These data are really compelling.”

In an interview with OncLive®, DiSilvestro, who is also the division director of gynecologic oncology in the Department of Obstetrics and Gynecology at The Warren Alpert Medical School of Brown University, discussed the pivotal SOLO-1 trial of maintenance olaparib in patients with BRCA-mutated ovarian cancer, updated survival data with the agent in this population, and the next steps for future research.

OncLive^®: Please provide some background on the pivotal SOLO-1/GOG-3004 trial.

DiSilvestro: SOLO-1 was a randomized phase 3 trial looking at the role of maintenance olaparib vs placebo in women with [newly diagnosed] advanced ovarian cancer and a BRCA mutation. [Patients] were randomly assigned in a 2:1 ratio to either olaparib or placebo and treated for [up to] 2 years or until disease progression, whichever came first. The preliminary primary end point was PFS and one of the secondary end points was OS. I [presented] a descriptive 7-year OS analysis [of follow-up data] at this meeting.

Could you expand on the study design? Why was 7-year OS selected as a clinically meaningful end point for this research?

There has been [research investigating at what point] women who have advanced ovarian cancer experience their greatest risk of death. There have been some eloquent data [presented] by [Robert L. Dood, MD, MSCE, of the University of Utah,] which demonstrated that the first 7 years after diagnosis are probably the principal risk years. [After this,] you begin to see a leveling of the curve. As such, in this descriptive analysis, we did not want to ‘spend’ too much alpha. [This means that] we wanted to look at the data, but not our primary OS end point.

What were the survival findings presented at the 2022 ESMO Congress?

The results were compelling: the median OS for the maintenance olaparib arm had yet to be reached and median OS for the placebo arm was [75.2] months; that yielded a hazard ratio of 0.55, [which translated to] a 45% reduction in the risk of death for those patients 7 years after their diagnosis. If you look at it in a different way, 67.0% of women in the olaparib arm were alive at 7 years after their diagnosis vs [45.6%] in the placebo arm.

What was reported in terms of time to first subsequent treatment?

[That was] another interesting variable that we looked at; [this] is really a proxy for progression-free analysis. The interesting thing here is [that] if you look at the women who are surviving in the olaparib arm, the majority are surviving without ever having received a subsequent therapy. Specifically, 7 years out [from their last administered treatment, 45.3%] of women in the olaparib arm have yet to receive subsequent therapy vs [20.6%] in the placebo arm. [Time to first subsequent treatment really is] an important variable.

What should be taken away from the analysis with regard to safety?

The adverse effect profile remains the same. The [incidence of] special events of interest, such as myelodysplastic syndromes [MDS] or acute myeloid leukemia [AML], and new primary malignancies, remains well balanced. We had 1 extra case of MDS or AML in each arm of the trial. As you can imagine, breast cancer [was the] most common [new primary malignancy] in this at-risk population [harboring BRCA mutations].

Is there anything else that you would like to add regarding the data presented?

[It was] exciting to see that separation of the curves [that we saw in an earlier analysis] persist; [this indicates that] there was an enduring benefit beyond the 2-year treatment cap. We treated people for 2 years, but 5 years later we're still seeing that separation. These data are really compelling.

Are any next steps planned for this research?

We [need to wait for the] OS [data to mature]. When we [performed] this analysis, the OS end point was set to be determined at 60% data maturity. Right now, we are at 38% maturity. That's a good thing, [because the event of interest is death]. That means that the event rate is low, and not as many people are dying. Hopefully it [takes] many years before [we] reach [this] because that would just mean [there are] more positive outcomes.

What is your key take-home message regarding this research?

Knowing [a patient’s] germline and tumor-based BRCA mutational status is critically important. It's [even more] critically important to [test for this] early in the lifespan of a woman with an advanced ovarian cancer, because that knowledge [provides the] power to make a great treatment decision going forward.

Reference

1. DiSilvestro P, Banerjee S, Colombo N, et al. Overall survival (OS) at 7-year (y) follow-up (f/u) in patients (pts) with newly diagnosed advanced ovarian cancer (OC) and a BRCA mutation (BRCAm) who received maintenance olaparib in the SOLO1/GOG-3004 trial. Ann Oncol. 2022;33(suppl 7):S779. doi:10.1016/j.annonc.2022.07.645