With a follow-up of >5 years, women with relapsed platinum-sensitive ovarian cancer and a BRCA mutation who participated in the multicenter phase 3 SOLO2 trial lived >1 year longer if randomized to maintenance olaparib compared with placebo, according to data released at the ASCO20 Virtual Scientific Program.
“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, at a press briefing prior to ASCO 2020. “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.”
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 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, from Initia Oncology Hospital Quirónsalud, Valencia, Spain.
Limited progress has been made in improving OS in patients with relapsed ovarian cancer, who usually receive multiple lines of chemotherapy. Gains in OS are difficult to demonstrate in ovarian cancer trials because of longer postprogression survival associated with crossover, he said.
SOLO2 enrolled 295 patients with relapsed high-grade serous or endometrial platinum-sensitive ovarian cancer and a BRCA mutation. All patients had received at least 2 prior lines of platinum-based chemotherapy and had responded to their most recent platinum regimen. They were randomized to olaparib 300 mg twice daily (n = 199) or placebo (n = 96), with treatment continuing until disease progression. Some 92% of patients randomized to placebo and 78% randomized to olaparib discontinued study treatment, the main reason being disease progression (80% in the placebo arm vs 49% in the olaparib arm).
In the primary analysis of SOLO2, maintenance olaparib led to a significant improvement in progression-free survival of 15.6 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,” Dr Poveda said. An exploratory analysis performed to adjust for impact of crossover to subsequent PARP inhibitor therapy found an improvement of 16.3 months in OS with maintenance olaparib over placebo.
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 (hazard ratio [HR], 0.37; P <.0001).
Among the 286 patients enrolled with a confirmed germline BRCA mutation using the Myriad BRACAnalysis 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 (HR, 0.71; P = .0306).
“Twenty-two percent of patients received maintenance olaparib for ≥5 years, reflecting the therapeutic benefit and manageable tolerability of olaparib,” he said. Mean treatment duration was 17.4 months and 9 months in the olaparib and placebo arms, respectively.
“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.
He noted that olaparib is approved as maintenance therapy for ovarian cancer independent of BRCA status and is also approved for 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.