Treatment With PARP Inhibitors for Patients With Ovarian Cancer
During a Targeted Oncology case-based roundtable event, Paul D. DiSilvestro, MD, discussed the long-term results from the SOLO-1 trial of olaparib maintenance for patients with ovarian cancer. This is the first of 3 articles based on this event.
Targeted OncologyTM: 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%.
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