With follow-up of more than 5 years, women with relapsed platinum-sensitive ovarian cancer and a BRCA mutation who participated in the multicenter phase 3 SOLO2 clinical trial lived more than 1 year longer when randomized to maintenance therapy with the poly (ADP- ribose) polymerase (PARP) inhibitor olaparib (Lynparza) compared with placebo, according to data released at the ASCO 2020 virtual annual meeting.
“At 5 years, 42% of patients in the olaparib group and 33% of patients in the placebo group were alive,” said lead investigator Andrés Poveda, MD, Initia Oncology, Hospital Quirónsalud, Valencia, Spain, at an ASCO press briefing.
“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 added.
The final overall survival (OS) analysis of SOLO2 showed that with a median follow-up of 65 months, patients assigned to olaparib maintenance therapy had a median OS of 51.7 months compared with 38.8 months with placebo, after platinum-based chemotherapy.
“A median overall survival improvement of nearly 13 months is impressive in ovarian cancer and brings a substantial benefit to our patients. With the addition of overall survival data, this study helps usher in a new era of personalized medicine for women with this difficult-to-treat cancer,” said Dr Poveda.
Limited progress in OS has been made in patients with relapsed ovarian cancer, who usually receive multiple lines of chemotherapy. Gains in OS are difficult to demonstrate in ovarian cancer studies because of longer post–disease progression survival associated with crossover to treatment with a PARP inhibitor, he noted.
SOLO2 Clinical Trial
SOLO2 enrolled 295 patients with relapsed high-grade serous or endometrial platinum-sensitive relapsed ovarian cancer and a BRCA mutation. All patients received at least 2 previous lines of platinum-based chemotherapy and had responded to their most recent platinum regimen. The women were randomized to olaparib (N = 199) 300 mg twice daily or to placebo (N = 96), with treatment continuing until disease progression. Some 92% of patients randomized to placebo and 78% randomized to olaparib discontinued the study treatment, predominantly because of disease progression (80% in the placebo arm vs 49% in the olaparib arm).
In the primary analysis of SOLO2, maintenance treatment with olaparib led to a significant improvement in progression-free survival of 15.6 months versus placebo.
The OS improvement in the olaparib arm “is an impressive finding, particularly considering that 38% of patients who received placebo crossed over to receive subsequent PARP inhibitor therapy,” said Dr Poveda. An exploratory analysis performed to adjust for impact of crossover to subsequent PARP inhibitor therapy showed an improvement of 16.3 months in OS with maintenance olaparib over placebo.
At 5 years, 28% of patients who received olaparib versus 13% of patients who received placebo were alive and had not received subsequent therapy. The time to first subsequent therapy was 27.4 months in the olaparib arm versus 7.2 months in the placebo arm (hazard ratio [HR], 0.37; P <.0001).
Among the 286 patients enrolled in the study with a confirmed germline BRCA mutation using the Myriad BRCAnalysis test, the OS advantage with olaparib increased to 15 months, from 37.4 months in the placebo arm to 52.4 months in the olaparib arm (HR, 0.71; P = .0306).
“Twenty-two percent of patients received maintenance olaparib for 5 years or longer, reflecting the therapeutic benefit and manageable tolerability of olaparib,” Dr Poveda said. The mean treatment duration was 17.4 months and 9 months in the olaparib and placebo arms, respectively.
New Standard of Care
“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, FACP, FSCT, FASCO.
Dr Schilsky noted that olaparib was recently approved as first-line maintenance therapy for all women with ovarian cancer, independent of BRCA status, as well as maintenance therapy for women whose tumors have BRCA mutations.
“Without comparing the data from all the trials, I think the presumption is, it is beneficial in both groups of women, but my guess is that it’s more beneficial in women who have BRCA mutations,” Dr Schilsky said.