The follow-up results of more than 5 years of the multicenter phase 3 SOLO2 clinical trial of women with ovarian cancer were presented at the 2020 ASCO annual meeting, showing improved survival with the use of Lynparza (olaparib) compared with placebo.
Women with relapsed (coming back) ovarian cancer that is sensitive to platinum-based chemotherapy (platinum-sensitive cancer) who had a BRCA gene mutation (change) lived more than 1 year longer if they received maintenance therapy with olaparib compared with placebo, according to data presented at the meeting by lead investigator Andrés Poveda, MD, Initia Oncology, Hospital Quirónsalud, Valencia, Spain.
“At 5 years, 42% of patients in the olaparib group and 33% of patients in the placebo group were alive,” Dr. Poveda said. “These results demonstrate that olaparib [Lynparza] 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 analysis of SOLO2 showed that with an average follow-up of 65 months, patients who received treatment with olaparib had an average survival of 51.7 months compared with only 38.8 months among the patients who received 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 has been made in improving the survival of women with relapsed ovarian cancer, who usually receive multiple lines of chemotherapy. Furthermore, gains in overall survival are difficult to demonstrate in ovarian cancer studies, because of longer survival after disease progression that is associated with patients crossing over to the active treatment group from the placebo group, Dr. Poveda added.
The SOLO2 clinical trial included 295 patients with relapsed high-grade serous or endometrial platinum-sensitive relapsed ovarian cancer associated with a BRCA mutation. All patients received at least 2 previous lines of platinum-based chemotherapy and had responded to their most recent platinum-based treatment regimen.
The patients were randomized (divided into 2 groups) to receive olaparib twice daily or to placebo, and the treatment continued until disease progression. In all, 92% of the patients who received placebo and 78% of the patients who received olaparib discontinued the study, mostly because their cancer progressed during the study, including 80% of patients who received placebo and 49% of the patients who received olaparib.
In the primary analysis of SOLO2, maintenance treatment with olaparib led to a significant improvement of 15.6 months in the time without disease progression compared with placebo.
Olaparib belongs to the class of drugs called PARP inhibitors that are approved for the treatment of patients with ovarian cancer. Olaparib is also approved for use by women with ovarian cancer and a BRCA gene mutation.
The overall survival improvement in the olaparib group “is an impressive finding, particularly considering that 38% of placebo patients crossed over to receive subsequent PARP inhibitor therapy,” said Dr. Poveda.
An exploratory analysis performed to evaluate the impact of crossing over to a subsequent PARP inhibitor therapy showed an improvement of 16.3 months in overall survival with maintenance olaparib compared with 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 patients who received olaparib versus 7.2 months in the patients who received placebo.
Among the 286 patients enrolled with a germline BRCA mutation that was confirmed with the Myriad BRCAnalysis genomic test, the overall survival advantage with olaparib increased to 15 months, at 52.4 months in the olaparib group versus 37.4 months in the placebo group.
“Twenty-two percent of patients received maintenance olaparib for 5 years or more, reflecting the therapeutic benefit and manageable tolerability of olaparib,” Dr. Poveda said. The average treatment duration was 17.4 months with olaparib and 9 months with 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, FACP, FSCT, FASCO.
Dr. Schilsky noted that olaparib is approved as maintenance therapy for all women with ovarian cancer, as well as 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,” he said.