With more than 5 years of follow-up, results from the SOLO2 trial of olaparib maintenance in relapsed, high-grade serous or endometrioid ovarian cancer, including primary peritoneal or fallopian tube cancer, were reported and showed superiority of the agent over placebo.
A final analysis of the phase 3 SOLO2 trial (NCT01874353) examining olaparib (Lynarza) tablets as maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer and BRCA1/2 mutations following 2 or more prior platinum regimens showed a trend toward overall survival (OS) superiority versus placebo maintenance.
The results published in Lancet Oncology indicate 26% reduction in the risk of death with active versus placebo therapy (HR, 0.74; 95% CI, 95% CI, 0.54-1.00; P = .054), which represent a clinically meaningful improvement in this patient group.
“SOLO2 is the first phase 3 trial that provides final overall survival data for maintenance olaparib, the only PARP inhibitor with long-term follow-up data, in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation,” wrote the study authors who were led by Andrés Poveda, MD. “Although the improvement in overall survival with olaparib was not statistically significant, it is arguably clinically meaningful, and thus the findings support the use of maintenance olaparib in this patient group.”
The international, double-blind placebo-controlled trial enrolled patients with histologically confirmed, relapsed, high-grade serous or endometrioid ovarian cancer, including primary peritoneal or fallopian tube cancer, who had received at least 2 prior platinum regimens and were in objective response. Patients with either somatic or germline BRCA1/2 mutations were eligible, but all randomized patients were found to have germline mutations.
Patients were randomized in a 2:1 fashion to receive olaparib tablets (n = 196; 300 mg, administered as 150 mg tablets twice daily) or matching placebo (n = 99). The median follow-up in each group was 65.7 months and 64.5 months, respectively.
Median OS was 51.7 months (95% CI, 41.5-59.1) with olaparib versus 38.8 months (95% CI, 31.4-48.6) with placebo, with the hazard ratio unadjusted for the 38% of patients who received subsequent PARP inhibitor therapy. In a prespecified exploratory analysis of an adjusted placebo group, the median OS was 35.4 months (95% CI, 24.2-43.5) and an adjusted hazard ratio of 0.56 (95% CI, 0.35-0.97).
The mean total treatment duration was 29.1 months (standard deviation [SD], 24.7; interquartile range, 8.2-56.8) with olaparib versus 13.1 months (SD, 18.6; 3.7-11.0) with placebo.
At the final analysis, dose interruptions due to treatment-emergent adverse events occurred in 50% of the olaparib group and 19% of the placebo group, with corresponding rates of dose reductions at 28% and 3%. Treatment discontinuations resulting from treatment-emergent adverse events happened in 17% of the olaparib group and 3% of the placebo group.
Myelodysplastic syndrome or acute myeloid leukemia (MDS/AML) occurred in 8% of patients in the olaparib group versus 4% on placebo. This resulted in a relative risk of 2.03 (95% CI, 0.70-5.91) for developing MDS/AML with olaparib.
In a previous paper, the primary end point of progression-free survival was reported showing a statistically significant improvement with olaparib maintenance (HR, 0.30; 95% CI, 0.22-0.41; P <.0001) and a tolerable safety profile. These results serve to confirm those findings and represent a benefit of olaparib maintenance therapy in the setting of extended survival.
The investigators noted potential limitations, which included the absence of patients with somatic BRCA1/2 mutations in the cohort. Another is the post-hoc nature of the analyses, including for sensitivity which corrected for patients who were mis-stratified at randomization and the analysis evaluating the relative risk for developing MDS/AML with olaparib.
Poveda A, Floquet A, Ledermann JA, et al; SOLO2/ENGOT-Ov21 investigators. 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. 2021 March 18, 2021. doi: 10.1016/S1470-2045(21)00073-5