As reported in the Journal of Clinical Oncology by DiSilvestro et al, the 7-year follow-up of the phase III SOLO1/GOG 3004 trial showed a reduction in risk of death by almost half with maintenance olaparib vs placebo in newly diagnosed patients with advanced ovarian cancer and a BRCA1/2 mutation, although the difference did not meet the prespecified P value of < .0001 for significance.
The trial supported the December 2018 approval of olaparib in this setting on the basis of improved progression-free survival.
Study Details
In the trial, 391 patients in clinical response to platinum-based chemotherapy were randomly assigned 2:1 to receive olaparib at 300 mg twice daily (n = 260) or placebo (n = 131) for up to 2 years. A prespecified descriptive analysis of the secondary endpoint of overall survival was performed after 7 years of follow-up. The prespecified P value for significance for the comparison of overall survival was < .0001.
Key Findings
Median follow-up was 88.9 months (interquartile range [IQR] = 85.7–93.6 months) in the olaparib group and 87.4 months (IQR = 84.3–91.7 months) in the placebo group.
Median overall survival was not reached (95% confidence interval [CI] = not reached–not reached) in the olaparib group vs 75.2 months (95% CI = 65.4 months–not reached) in the placebo group (hazard ratio [HR] = 0.55, 95% CI = 0.40–0.76, P = .0004; did not reach P < .0001 required to declare statistical significance). The analysis was not adjusted for subsequent therapy; the survival benefit with olaparib was achieved despite receipt of a poly (ADP-ribose) polymerase inhibitor in a subsequent line of therapy in 44.3% of patients in the placebo group.
At 7 years, 67.0% of olaparib patients vs 46.5% of placebo patients were alive, and 45.3% vs 20.6% were alive and had not received a first subsequent treatment, respectively.
A total of 122 olaparib patients (47%) and 97 placebo patients (74%) received any subsequent therapy. The median time from random assignment to first subsequent therapy or death (data maturity = 59.6%) was 64.0 months (95% CI = 47.7–93.2 months) in the olaparib group vs 15.1 months (95% CI = 12.7–20.5 months) in the placebo group (HR = 0.37, 95% CI = 0.28–0.48). The median time to second subsequent therapy or death (data maturity = 48.6%) was 93.2 months (95% CI = 84.2 months–not reached) in the olaparib group vs 40.7 months (95% CI = 32.9–54.4 months) in the placebo group (HR = 0.50, 95% CI = 0.37–0.67).
Since the primary analysis in May 2018, one new case of myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) had been reported in each treatment group. Over 7 years, MDS/AML had occurred in 4 olaparib patients (1.5%) and 1 placebo patient (0.8%). Since the 5-year follow-up in March 2020, 6 new primary malignancies occurred in olaparib patients and 3 had occurred in placebo patients. Over 7 years, new primary malignancies had occurred in 14 olaparib patients (5.4%) and 8 placebo patients (6.2%).
The investigators concluded, “Results indicate a clinically meaningful, albeit not statistically significant according to prespecified criteria, improvement in overall survival with maintenance olaparib in patients with newly diagnosed advanced ovarian cancer and a BRCA mutation and support the use of maintenance olaparib to achieve long-term remission in this setting; the potential for cure may also be enhanced. No new safety signals were observed during long-term follow-up.”
Paul DiSilvestro, MD, of Women & Infants Hospital, Providence, Rhode Island, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by AstraZeneca and the current analysis is part of an alliance between AstraZeneca and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co Inc. For full disclosures of the study authors, visit ascopubs.org.
