As reported in The Lancet Oncology by Susana Banerjee, MBBS, PhD, and colleagues, 5-year follow-up of the pivotal phase III SOLO-1/GOG 3004 trial has shown a median progression-free survival of 56 months with maintenance olaparib following response to platinum-based chemotherapy in newly diagnosed patients with advanced BRCA-mutant ovarian cancer.
The study supported the December 2018 approval of olaparib in this setting on the basis of improved investigator-assessed progression-free survival vs placebo in the primary analysis.
Susana Banerjee, MBBS, PhD
Study Details
The double-blind trial included 391 patients from sites in 15 countries with high-grade serous or endometrioid disease with complete or partial response after platinum-based chemotherapy. They were randomly assigned 2:1 between September 2013 and March 2015 to receive maintenance therapy with olaparib at 300 mg twice daily (n = 260) or placebo (n = 131) for up to 2 years.
Key Findings
At data cutoff for the current post hoc analysis (March 2020), median follow-up was 4.8 years (interquartile range [IQR] = 2.8–5.3 years) in the olaparib group and 5.0 years (IQR = 2.6–5.3 years) in the placebo group. Median treatment duration was 24.6 months (IQR = 11.2–24.9 months) vs 13.9 months (IQR = 8.0–24.8 months).
Median progression-free survival was 56.0 months (95% confidence interval [CI] = 41.9 months–not reached) in the olaparib group vs 13.8 months (95% CI = 11.1–18.2 months) in the placebo group (hazard ratio [HR] = 0.33, 95% CI = 0.25–0.43). Rates at 5 years were 48% vs 21%.
In subgroup analysis, median progression-free survival was 40.6 months (95% CI = 27.9 months–not reached) vs 11.1 months (95% CI = 8.3–13.8 months) among patients with higher clinical risk (those with stage IV disease or those with stage III disease who had either residual disease following primary debulking surgery or had undergone interval surgery; HR = 0.34, 95% CI = 0.24–0.49) and not reached (95% CI = not reached–not reached) vs 21.9 months (95% CI = 13.7–33.4 months) among those with lower clinical risk (stage III disease with no residual disease following primary debulking surgery; HR = 0.38, 95% CI = 0.25–0.59).
At the data cutoff, 40% of patients in the olaparib group and 72% in the placebo group had received a first subsequent therapy. Median second progression-free survival was not reached vs 42.1 months (HR = 0.46, 95% CI = 0.33–0.65). Among 189 vs 101 patients with complete response after platinum-based chemotherapy, median recurrence-free survival was not reached vs 15.3 months (HR = 0.37, 95% CI = 0.27–0.52); 5-year rates were 52% vs 22%.
KEY POINTS
- Median progression-free survival was 56.0 months in the olaparib group vs 13.8 months in the placebo group.
- In subgroup analysis, median progression-free survival was 40.6 months among patients with higher clinical risk (those with stage IV disease or those with stage III disease who had either residual disease following primary debulking surgery or had undergone interval surgery) and not reached among those with lower clinical risk (stage III disease with no residual disease following primary debulking surgery).
Overall survival data were not mature at time of analysis. At time of analysis, death had occurred in 27% vs 40% of patients.
No new safety signals were observed. No new cases of myelodysplastic syndrome or acute myeloid leukemia (AML) were reported in the olaparib group since the primary data cutoff (AML had occurred in 3 vs 0 patients by data cutoff). Overall new primary malignancies have been observed in eight (3%) vs five (4%) patients; three (1%) vs two (2%) have been observed since primary data cutoff.
The investigators stated, “In a setting where median overall survival from the initiation of chemotherapy is around 5 years, our findings show that almost half of patients who received maintenance olaparib remained progression-free 5 years after randomization, following chemotherapy.”
They concluded, “For patients with newly diagnosed advanced ovarian cancer and a BRCA mutation, after, to our knowledge, the longest follow-up for any randomized controlled trial of a poly (ADP-ribose) polymerase (PARP) inhibitor in this setting, the benefit derived from 2 years’ maintenance therapy with olaparib was sustained beyond the end of treatment, extending median progression-free survival past 4.5 years. These results support the use of maintenance olaparib as a standard of care in this setting.”
Dr. Banerjee, of The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by AstraZeneca and Merck Sharpe & Dohme, a subsidiary of Merck & Co. For full disclosures of the study authors, visit thelancet.com.
