With follow-up of >5 years, 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 (Lynparza) compared with placebo, according to data released at the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program.
At 5 years, 42% of patients in the olaparib group and 33% of patients in the placebo group were alive, reported SOLO2 lead investigator Andrés Poveda, MD, Medical Coordinator, Gynaecological Oncology Clinical Area, Valencian Oncology Institute, Initia Oncology, Hospital Quirónsalud, Valencia, Spain. “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 overall survival (OS) analysis of SOLO2 showed that with a median follow-up of 65 months, patients assigned to olaparib had a median OS of 51.7 months compared with 38.8 months for the 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.
SOLO2 enrolled 295 patients with relapsed high-grade serous or endometrial platinum-sensitive relapsed ovarian cancer and a BRCA mutation. All 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), with treatment continuing until disease progression.
In the primary analysis of SOLO2, maintenance olaparib led to a significant improvement in progression-free survival of 13.6 months over placebo.
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,” said Dr Poveda.
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 olaparib patients versus 13% of placebo patients 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 exploratory analysis performed to adjust for impact of crossover to subsequent poly (ADP-ribose) polymerase (PARP) inhibitor therapy found an improvement of 16.3 months in OS with maintenance olaparib over placebo.
“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.