Olaparib maintenance confers durable PFS benefit in advanced BRCA-mutated ovarian cancer
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Olaparib maintenance significantly extended 5-year PFS for women with advanced BRCA-positive ovarian cancer, according to results presented at the virtual Society of Gynecologic Oncology Annual Meeting on Women’s Cancer.
The PFS benefit observed with olaparib (Lynparza, AstraZeneca) appeared consistent across women with low-risk and high-risk disease, results of the SOLO-1 trial showed.
“These results further support the use of maintenance olaparib as a standard of care for women with newly diagnosed advanced ovarian cancer and a BRCA mutation, and suggest the possibility of long-term remission or even cure for some patients,” researcher William Bradley, MD, gynecologic oncologist at Froedtert and Medical College of Wisconsin, said during a presentation.
Only about one-third to one-half of women diagnosed with advanced ovarian cancer survive 5 years, and patients are at high risk for relapse. Treatment goals in this setting include delaying recurrence and — for some patients — increased chance of cure, according to study background.
Olaparib is a poly(ADP-ribose) polymerase (PARP) inhibitor.
The randomized SOLO-1 trial included 391 women with newly diagnosed, stage III or stage IV, high-grade serous or endometrioid ovarian, primary peritoneal or fallopian tube cancer. All women had BRCA1 or BRCA2 mutations, had ECOG performance status 0 or 1, had undergone cytoreductive surgery, and were in clinical complete response or partial response after platinum-based chemotherapy.
Researchers assigned 260 women to maintenance olaparib dosed at 300 mg twice daily for 2 years or until disease progression. The other 131 women received placebo.
Investigator-assessed PFS served as the primary endpoint. Secondary endpoints included PFS2, time to subsequent therapy and safety.
Results of the primary analysis — based on data cutoff of May 17, 2018 — showed women assigned olaparib achieved significantly longer median PFS (not reached vs. 13.8 months; HR = 0.3; 95% CI, 0.23-0.41).
At this year’s Society of Gynecologic Oncology meeting, Bradley presented 5-year follow-up results, which showed 48% of women assigned olaparib and 21% of those assigned placebo remained progression free.
Results showed significantly longer median PFS with olaparib (56 months vs. 13.8 months; HR = 0.33; 95% CI, 0.25-0.43).
Researchers also evaluated PFS based on disease risk. The higher-risk group included women with stage IV disease, those with stage III disease who had residual disease after primary debulking, and those with stage III disease who underwent interval surgery. The lower-risk group included those with stage III disease who had no residual disease after primary debulking.
The PFS benefit with olaparib appeared consistent in the higher-risk subgroup (5-year PFS, 42% vs. 17%; median, 40.6 months vs. 11.1 months; HR = 0.35; 95% CI, 0.25-0.49) and lower-risk subgroup (5-year PFS, 56% vs. 25%; median, not reached vs. 21.9 months; HR = 0.38; 95% CI, 0.25-0.59).
Secondary data outcomes also supported the benefit of olaparib, including median time to second progression or death (overall cohort, not reached vs. 42.1 months; HR = 0.46; 95% CI, 0.33-0.65; patients in complete response at baseline, not reached vs. 52.9 months; HR = 0.48; 95% CI, 0.32-0.71) and time to subsequent therapy (overall cohort, not reached vs. 40.7 months; HR = 0.46; 95% CI, 0.34-0.63; patients in complete response at baseline, not reached vs. 47.7 months; HR = 0.5; 95% CI, 0.35-0.72).
The safety profile of olaparib remained consistent with that reported in the primary analysis, according to researchers.
A higher percentage of olaparib-treated patients experienced any adverse event (98% vs. 92%), grade 3 or higher adverse events (40% vs. 19%) and serious adverse events (21% vs. 13%). A higher percentage of women assigned olaparib experienced adverse events that led to dose interruption (52% vs. 17%), dose reduction (29% vs. 3%) or treatment discontinuation (12% vs. 3%).
During the entire SOLO-1 study, a higher percentage of women in the olaparib group developed myelodysplastic syndrome (MDS) or acute myeloid leukemia (1% vs. 0%). No additional cases of MDS or AML occurred after the initial primary analysis.
Four percent of women assigned placebo and 3% of those assigned olaparib developed a new primary malignancy during the study period.
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Deborah Armstrong, MD
We can see very significant differences in outcomes after patients completed therapy. Looking at the overall group and patients who had good prognosis, what you see in terms of time to second progression or death or time to subsequent therapy are really tight HRs. Even patients with BRCA mutations who have suboptimal disease or stage IV disease but get neoadjuvant therapy really maintain a significant benefit with the use of PARP inhibitors, and this is important information for us.
Importantly, no additional secondary hematologic malignancies were identified. This may be telling us that getting PARP inhibitors earlier for patients who had less chemotherapy may be important in terms of the risk for MDS or AML.
We await OS data if we can get it from this study. As Dr. Bradley said, maybe we can start to use the “C” word — not cancer, but cure — for some of these patients.
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Bradley W, et al. Abstract 10520. Presented at: Society of Gynecologic Oncology Annual Meeting on Women’s Cancer (virtual meeting); March 19-25, 2021.
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