Long-Term Follow-Up Shows Olaparib’s Efficacy in Ovarian Cancer

Paul D. DiSilvestro, MD

Director, Program in Women’s Oncology

Women & Infants Hospital of Rhode Island and Care New England Health System

Division director, Gynecologic Oncology

Department of Obstetrics and Gynecology

Warren Alpert Medical School of Brown University

Providence, RI

Targeted Oncology^TM: Could you discuss the SOLO-1 trial (NCT01844986) of olaparib (Lynparza) in patients with ovarian cancer and its initial results?

DISILVESTRO: This trial was olaparib maintenance after first-line chemotherapy, and this was a 2:1 randomization of olaparib versus placebo for up to 2 years or until progression or toxicity. The primary investigator-assessed outcome was progression-free survival [PFS]. The secondary outcomes were overall survival [OS], time to first subsequent therapy or death, and some other end points. So 391 patients were randomly assigned.¹ Most patients had [no evidence of disease at enrollment]. About 80% had a complete response to primary treatment prior to entering the trial.

If we look at the baseline characteristics, the vast majority had stage III disease, and the majority were BRCA1-positive, otherwise had good performance status, and had received 6 cycles of chemotherapy up front.

The results of the SOLO-1 trial at the initial presentation showed there was a 70% reduction in the risk of progression or death for women given olaparib versus the placebo.¹ If you look closely at the [Kaplan-Meier] curves, there is a separation in the curves that begins early, and once they hit the 2-year treatment cap, we see a persistence in the separation. Physicians have wondered [if] 2 years is enough. I think what we’ve seen is that it creates the difference by the time they’re 2 years out and you maintain the difference going forward. That’s the basis for maintaining that 2-year cap.

What were the outcomes of more recent analyses from this trial?

If we look at the subgroup analysis, above and beyond [Kathleen N. Moore, MD, MS’s] presentation, there have been some further looks into subsets.² The bottom line is it doesn’t matter what you look at. Every single subset or question you can think about from a stratification perspective favors olaparib versus placebo, so there is a pretty convincing argument that there is not a subset of patients within this context that would not benefit from olaparib.

I had the opportunity to present the OS data at the 2022 European Society for Medical Oncology Annual Meeting for 7 years of follow-up.³ We had 88 months of follow-up in both arms of the trial; the median OS was not yet reached in the olaparib arm and was 75 months in the placebo arm, [translating to] a 45% reduction in the risk of progression or death, with a ­P value of .0004.

[This result was] not significant. The target was set at [a P value of] .0001. The OS end point in this study was only at 38% data maturity, and the OS statistically is determined to occur at 60%. So we have a long way to go until the prespecified OS end point. Sixty-seven percent of patients were alive in the olaparib arm versus 46% in the placebo arm. I think the key data to look at is the time to first subsequent therapy; if you look at those data, 46% in the olaparib arm have yet to ever receive a second therapy at 7 years out versus 20% in the placebo arm. We’re not technically allowed to use the word cure [in this treatment setting], but that shows us the potential for doing so at 7 years out.

[In terms of] adverse events, patients hadn’t been treated for 5 years so there’s not an increase in the adverse events per se.⁴ There was 1 additional patient in each arm that experienced myelodysplastic syndrome or acute myeloid leukemia. Overall, the rate is low, less than 2%.

_References:

_{1. Moore K, Colombo N, Scambia G, et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 2018;379(26):2495-2505. doi:10.1056/NEJMoa1810858}

_{2. DiSilvestro P, Colombo N, Scambia G, et al. Efficacy of maintenance olaparib for patients with newly diagnosed advanced ovarian cancer with a BRCA mutation: subgroup analysis findings from the SOLO1 trial. J Clin Oncol. 2020;38(30):3528-3537. doi:10.1200/JCO.20.00799}

_{3. 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; abstr 5170). doi:10.1016/annonc/annonc1054}

_{4. Banerjee S, Moore KN, Colombo N, et al. Maintenance olaparib for patients with newly diagnosed advanced ovarian cancer and a BRCA mutation (SOLO1/GOG 3004): 5-year follow-up of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2021;22(12):1721-1731. doi:10.1016/S1470-2045(21)00531-3}