Does olaparib improve overall survival in patients with recurrent ovarian cancer and BRCA mutation?
Olaparib, a poly(ADP-ribose) polymerase (PARP) enzyme inhibitor, in tablet form is indicated, among other things, for the maintenance treatment of adult patients with platinum-sensitive recurrent high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who respond (complete or partial response) to platinum-based chemotherapy. Its efficacy in this indication in terms of prolonging progression-free survival and overall survival was addressed by the phase III study presented below.
Study Methodology and Population
The multicenter randomized double-blind SOLO2 study included a total of 295 platinum-sensitive patients with recurrent high-grade serous or endometrioid ovarian cancer, including fallopian tube and primary peritoneal cancer, and a confirmed BRCA1/BRCA2 gene mutation. All patients had to have undergone ≥ 2 lines of platinum chemotherapy with complete or partial response to the last platinum chemotherapy. They were randomized in a 2:1 ratio into 2 arms. Stratification was based on the response to previous chemotherapy (partial vs. complete response) and the time elapsed since the last platinum chemotherapy (6–12 months vs. > 12 months). A total of 196 patients received olaparib in tablet form (300 mg 2× daily per os), while 99 received placebo.
The primary endpoint was progression-free survival (PFS) assessed by investigators, with secondary endpoints including overall survival (OS).
Results
At the time of the data evaluation (February 2020) for the final analysis, patients in both arms had been followed for an average of 65 months from the start of treatment. During the follow-up period, more than one-third of patients (38%) initially receiving placebo transitioned to subsequent PARP inhibitor therapy.
Patients on olaparib had a 70% reduction in the risk of disease progression, and a statistically significant increase in PFS by 13.6 months was observed compared to the placebo arm (19.1 vs. 5.5 months; hazard ratio [HR] 0.30; 95% confidence interval [CI] 0.22–0.41; p < 0.0001).
Long-term benefits of olaparib compared to placebo were also observed in terms of overall survival (51.7 vs. 38.8 months; HR 0.74; 95% CI 0.54–1.00; p = 0.0537). According to the Kaplan-Meier estimate, after 5 years, 42% of patients on olaparib survived compared to 33% of those on placebo; 5-year survival without subsequent therapy was achieved by 28% of patients on olaparib vs. 13% on placebo.
Conclusion
The analysis of the SOLO2 study indicates that olaparib prolongs progression-free and overall survival in patients with platinum-sensitive recurrent ovarian cancer and confirmed BRCA1/BRCA2 gene mutation, providing significant benefit in the treatment of this indication.
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Sources:
1. Poveda A., Floquet A., Ledermann J. A. et al. Final overall survival (OS) results from SOLO2/ENGOT-ov21: a phase III trial assessing maintenance olaparib in patients (pts) with platinum-sensitive, relapsed ovarian cancer and a BRCA mutation. J Clin Oncol 2020; 38 (15_suppl.): 6002, doi: 10.1200/JCO.2020.38.15_suppl.6002.
2. SPC Lynparza, date of last text revision 3. 11. 2020. Available at: www.ema.europa.eu/en/documents/product-information/lynparza-epar-product-information_cs.pdf¨
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