Findings from the phase 3 SOLO1/GOG-3004 trial presented at ESMO 2022 support maintenance therapy with olaparib in women with newly diagnosed advanced ovarian cancer.
After 7 years of follow-up, maintenance therapy with olaparib (Lynparza) for 2 years reduced risk for death by 45% vs placebo in patients with newly diagnosed advanced, BRCA-positive ovarian cancer, according to data from the phase 3 SOLO1/GOG-3004 trial (NCT01844986) presented at the 2022 European Society for Medical Oncology Congress.1-2
“These results support the use of maintenance olaparib to achieve long-term remission in women with newly diagnosed advanced ovarian cancer and a BRCA mutation. The potential for cure may also be enhanced,” Paul A. DiSilvestro, MD, director of the Program in Women’s Oncology for Women & Infants Hospital of Rhode Island and Care New England Health System, and division director of gynecologic oncology in the Department of Obstetrics and Gynecology at The Warren Alpert Medical School of Brown University, said during a presentation of the data, which were simultaneously published in the Journal of Clinical Oncology.2
As of the data cutoff of March 7, 2022 (data maturity, 38.1%), median overall survival (OS) was not reached with olaparib treatment, compared with 75.2 months with placebo treatment (HR, 0.55; 95% CI, 0.40-0.76; P = .0004). The 7-year OS rates were 67.0% in the olaparib arm and 46.5% in the placebo arm. The median duration of follow-up in the olaparib and placebo arms were 88.9 months (range, 85.7-93.6) and 87.4 months (range, 84.3–91.7), respectively.
In total, 45.3% of patients in the olaparib arm and 20.6% in the placebo arm had still not received a first subsequent treatment, while 44.3% of patients given placebo received a PARP inhibitor in a subsequent line of therapy, compared with 14.6% of patients in the olaparib group.
“The OS benefit was seen despite over 40% of patients in the placebo group receiving subsequent PARP inhibitor therapy,” DiSilvestro said.
The time to first subsequent therapy or death (TFST) was also substantially delayed with olaparib, compared with placebo (median, 64.0 months vs 15.1 months; HR 0.37; 95% CI, 0.28-0.48), and this benefit extended beyond first subsequent therapy into the time to second subsequent therapy or death (TSST) (93.2 months vs 40.7 months; HR 0.50; 95% CI, 0.37-0.67).
“These 7-year results provide further confirmation that the benefit of maintenance olaparib extends well beyond its 2-year treatment cap,” DiSilvestro added.
No new safety signals were observed during the 7-year follow-up.
The incidence of MDS/AML remained low in the olaparib and placebo arms (1.5% vs 0.8%, respectively) and new primary malignancies remained balanced between arms (5.4% vs 6.2%). Pneumonitis occurred in 5 patients treated with olaparib.
The most frequent adverse events in the olaparib and placebo groups included nausea (77.7% vs 37.7%, respectively), fatigue/asthenia (64.2% vs 41.5%), vomiting (40.0% vs 14.6%), anemia (40.0% vs 10.0%), diarrhea 34.6% vs 24.6%), arthralgia (28.8% vs 30.0%), constipation (27.7% vs 19.2%), abdominal pain (25.8% vs 19.2%), headache (23.1% vs 23.8%), neutropenia (23.1% vs 11.5%), dysgeusia (21.5% vs 3.8%), dizziness (20.4% vs 15.4%), decreased appetite (20.4% vs 10.0%), and cough (16.9% vs 21.5%).
“Ten-year survival in women with newly diagnosed advanced epithelial ovarian cancer is 17%. Relapsed advanced ovarian cancer is typically incurable, highlighting the need for effective first-line therapies that delay relapse, prolong survival, and enhance the potential for cure,” DiSilvestro explained. “We reported a descriptive analysis of OS after 7 years of follow-up in SOLO1, a clinically relevant timepoint for survivorship, and the longest follow-up for any PARP inhibitor in newly diagnosed advanced ovarian cancer
In the randomized, double-blind, placebo-controlled, phase 3 trial, which was conducted across 15 countries, patients were randomly assigned 2:1 to receive either 300 mg of olaparib twice daily (n = 260) or placebo (n = 131) orally as maintenance monotherapy for up to 2 years or until disease progression.
Investigator-assessed PFS served as the primary end point. Secondary end points included OS, TFST, TSST, and safety.
To be eligible for enrollment, patients had to be 18 years or older; have newly diagnosed, FIGO stage III to IV, high-grade serous or endometrioid ovarian, primary peritoneal or fallopian tube cancer; a BRCA mutation; ECOG performance status of 0 or 1; cytoreductive surgery; and clinical complete or partial responses after platinum-based chemotherapy.
In the olaparib arm, the majority of patients had stage III disease (84.6%) and a BRCA1 mutation (73.5%). In total, 61.9% of patients underwent upfront surgery, while 36.2% had interval cytoreductive surgery, of which 81.9% of patients reported with a clinical complete response.
Initial findings, presented in 2018, showed that after a median follow-up of 41 months, the risk for disease progression or death was 70% lower with olaparib, compared with placebo (HR, 0.30; 95% CI, 0.23-0.41; P < .001), with a median PFS not reached with olaparib vs 13.8 months with placebo. The 3-year PFS rates were 60.4% and 26.9%, respectively.3
In 2021, investigators reported an updated, post-hoc analysis of PFS from the trial, after 5 years of follow-up. The data cutoff for this updated, post-hoc analysis was March 5, 2020. In the 5-year post-hoc analysis, median PFS was 56.0 months (95% CI, 41.9-not reached) with olaparib, compared with 13.8 months (95% CI, 11.1-18.2) with placebo (HR, 0.33; 95% CI, 0.25-0.43). Moreover, 48.3% of patients in the olaparib group vs 20.5% of patients in the placebo group were progression free at 5 years.4