Olaparib maintenance monotherapy not only delays disease progression but also improves overall survival (OS) in women with platinum-sensitive relapsed ovarian cancer and a BRCA mutation.
According to data released at this year’s American Society of Clinical Oncology (ASCO) Virtual Scientific Program, with >5 years’ follow-up, women with relapsed platinum-sensitive ovarian cancer and a BRCA mutation who participated in the multicenter phase 3 SOLO2 clinical trial lived >1 year longer if randomized to maintenance olaparib compared with placebo. As reported by SOLO2 lead investigator Andrés Poveda, MD, Medical Coordinator, Gynaecological Oncology Clinical Area, Valencian Oncology Institute, Initia Oncology, Hospital Quirónsalud, Valencia, Spain, at 5 years, 42% of patients in the olaparib group and 33% in the placebo group were alive. “These results demonstrate that olaparib maintenance monotherapy not only delays disease progression but also improves overall survival in women with platinum-sensitive relapsed ovarian cancer and a BRCA mutation,” he said.
The final OS analysis of SOLO2 showed that with a median follow-up of 65.0 months, patients assigned to olaparib had a median OS of 51.7 months versus 38.8 months for patients assigned to placebo after platinum-based chemotherapy. “A median OS improvement of nearly 13 months is impressive in ovarian cancer and brings a substantial benefit to our patients. With the addition of OS data, this study helps usher in a new era of personalized medicine for women with this difficult-to-treat cancer,” said Dr Poveda.
A total of 295 patients with relapsed high-grade serous or endometrial platinum-sensitive relapsed ovarian cancer and a BRCA mutation were enrolled in SOLO2. All patients received ≥2 previous lines of platinum-based chemotherapy and had responded to their most recent platinum regimen. They were randomized to olaparib (N = 196) 300 mg twice daily or placebo (N = 99). Treatment continued until disease progression.
In the primary analysis of SOLO2, a significant improvement in progression-free survival of 13.6 months over placebo occurred with maintenance olaparib. According to Dr Poveda, the OS improvement in the olaparib arm “is an impressive finding, particularly considering that 38% of placebo patients crossed over to receive subsequent PARP inhibitor therapy.”
Among the 286 patients enrolled with a confirmed germline BRCA mutation using the Myriad BRCAnalysis test, the OS advantage with olaparib increased to 15 months—52.4 months in the olaparib arm versus 37.4 months in the placebo arm (hazard ratio [HR], 0.71; P = .0306).
At 5 years, 28% of patients who received olaparib versus 13% of patients who received placebo were alive and had not received subsequent therapy. Time to first subsequent therapy was 27.4 months in the olaparib arm versus 7.2 months in the placebo arm (HR, 0.37; P <.0001).
An improvement of 16.3 months in OS with maintenance olaparib over placebo was found in an exploratory analysis performed to adjust for the impact of crossover to subsequent poly (ADP-ribose) polymerase (PARP) inhibitor therapy. “This study confirms that the PARP inhibitor olaparib should be the standard maintenance therapy for patients with BRCA-related relapsed ovarian cancer responding to platinum-based chemotherapy—a significant advance for women with a cancer that has a historically poor prognosis,” commented ASCO Chief Medical Officer and Executive Vice President Richard L. Schilsky, MD.
Source: Poveda A, et al. J Clin Oncol. 2020;38(15_suppl). Abstract 6002.