Overall Survival With Olaparib vs Placebo Maintenance in Patients With Platinum-Sensitive Relapsed Ovarian Cancer and BRCA1/2 Mutation

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As reported in The Lancet Oncology by Andrés Poveda, MD, and colleagues, the phase III SOLO2/ENGOT-Ov21 trial has shown a large numeric but statistically nonsignificant improvement in the secondary endpoint of overall survival with olaparib tablet maintenance therapy vs placebo in patients with platinum-sensitive relapsed ovarian cancer and a BRCA1/2 mutation.1

The primary analysis of the trial supported the August 2017 regular approval of olaparib tablets in this setting on the basis of a significant improvement in progression-free survival.

Study Details

In the double-blind trial, 295 patients from sites in 16 countries were randomly assigned 2:1 between September 2013 and November 2014 to receive 300-mg olaparib tablets twice daily (n = 196) or placebo (n = 99). Treatment continued until disease progression or other discontinuation criteria were met; treatment could continue beyond disease progression if the investigator deemed the patient was experiencing benefit and did not meet other discontinuation criteria. Patients had relapsed, high-grade serous

Andrés Poveda, MD

Andrés Poveda, MD

or high-grade endometrioid ovarian cancer, including primary peritoneal or fallopian tube cancer; had received at least two previous lines of platinum-based chemotherapy and were in objective response to their most recent platinum regimen; and had platinum-sensitive disease with a BRCA1/2 mutation. The primary analysis showed a significant improvement with olaparib treatment in progression-free survival (median = 19.1 vs 5.5 months, hazard ratio [HR] = 0.30, 95% confidence interval [CI] = 0.22–0.41, P < .0001). This final analysis of the trial reported on overall survival, a key secondary endpoint.

Overall Survival

At the final overall survival analysis (performed at 61% data maturity), the median follow-up for overall survival was 65.7 months (interquartile range [IQ] = 63.6–69.3 months) in the olaparib group and 64.5 months (IQR = 63.4–68.7 months) in the placebo group among censored patients. After discontinuation of study treatment, subsequent anticancer therapy was received by 66% of the olaparib group vs 82% of the placebo group, including platinum-containing chemotherapy in 45% vs 43%, another chemotherapy-containing regimen (excluding platinum and bevacizumab) in 38% vs 56%, and PARP inhibitor therapy in 10% vs 38%.

Median overall survival was 51.7 months (95% CI = 41.5–59.1 months) in the olaparib group vs 38.8 months (95% CI = 31.4–48.6 months) in the placebo group (HR = 0.74, 95% CI = 0.54–1.00, P = .054), with an estimated 5-year survival rate of 42% vs 33%. In a prespecified exploratory analysis adjusting for subsequent PARP inhibitor therapy in 38% of the placebo group in the full analysis set, median overall survival was 51.7 months (95% CI = 41.5–59.1 months) in the olaparib group vs 35.4 months (95% CI = 24.2–43.5 months) in the placebo group (HR = 0.56, 95% CI = 0.35–0.97).

Median time to first subsequent therapy or death was 27.4 months vs 7.2 months (HR = 0.37, 95% CI = 0.28–0.48). The estimated proportion of patients who were alive and had not received a first subsequent treatment at 5 years was 28% vs 13%.

Adverse Events

the mean total treatment duration was 29.1 months (IQR = 8.2–56.8 months) for olaparib and 13.1 months (IQR = 3.7–11.0 months) for placebo. The most common grade ≥ 3 adverse event in the olaparib group was anemia (21% vs 2%). With longer follow-up (data cutoff in February 2020), serious adverse events occurred in 26% vs 8% of patients, with the most common in the olaparib group being anemia (4%), intestinal obstruction (2%), myelodysplastic syndromes (2%), and constipation (2%). Treatment-related adverse events led to discontinuation of treatment in 13% vs 1% of patients, with the most common causes in the olaparib group being anemia (4%), acute myeloid leukemia (2%), myelodysplastic syndromes (1%), neutropenia (1%), and thrombocytopenia (1%). Treatment-related adverse events led to death in six patients (3%) in the olaparib group and none in the placebo group, with causes in the olaparib group consisting of myelodysplastic syndromes in three patients and acute myeloid leukemia in three patients.


  • No significant difference in overall survival was observed between olaparib vs placebo maintenance.
  • Median overall survival was 51.7 months vs 38.8 months.

The investigators concluded: “Olaparib provided a median overall survival benefit of 12.9 months compared with placebo in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation. Although statistical significance was not reached, these findings are arguably clinically meaningful and support the use of maintenance olaparib in these patients.” 

Disclosure: The study was supported by AstraZeneca and Merck. Dr. Poveda has served as a consultant or advisor to AstraZeneca, Clovis Oncology, GSK, PharmaMar, and Roche; and has received travel, accomodations, or expenses from PharmaMar.


1. Poveda A, Floquet A, Ledermann JA, et al: Olaparib tablets as maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): A final analysis of a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol 22:620-631, 2021.