Maintenance therapy with AstraZeneca’s Lynparza (olaparib) extended survival by more than one year in women with BRCA-mutated relapsed ovarian cancer, whose tumors responded to platinum-based chemotherapy, final results from the SOLO-2 Phase 3 clinical trial show.
Trial findings, “Final overall survival (OS) results from SOLO2/ENGOT-ov21: A phase III trial assessing maintenance olaparib in patients (pts) with platinum-sensitive, relapsed ovarian cancer and a BRCA mutation,” will be presented at the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting, which will be held online May 29–31. A video presentation is available now.
Lynparza is a so-called PARP inhibitor as it works by blocking the PARP enzyme, which plays a role in repairing DNA errors in cells. The oral medication is particularly effective in cancers with mutations in other DNA-repairing genes, such as BRCA1 and BRCA2, because they rely mainly on the PARP enzymes to repair DNA damage and avoid tumor cell death.
SOLO-2 (NCT01874353) evaluated Lynparza as a maintenance therapy for women with relapsed BRCA-related ovarian cancer who had responded to their most recent platinum-based chemotherapy after having received at least one more line of chemotherapy. The trial was funded by AstraZeneca and MSD, known as Merck in the U.S. and Canada.
A total of 195 women were treated with 300 mg tablets of Lynparza given twice daily, and 99 received a placebo. Treatment was given until disease progression or the occurrence of serious toxicity.
Results showed that 42.1% of women on Lynparza were alive at five years of follow up, compared to 33.2% of women on a placebo. Median overall survival was 51.7 months with Lynparza and 38.8 months with a placebo, meaning survival extension of 12.9 months with the therapy.
“A median overall survival improvement of nearly 13 months is impressive in ovarian cancer and brings a substantial benefit to our patients,” Andres Poveda, MD, the study’s lead lead author, said in a press release. “With the addition of overall survival data, this study [SOLO-2] helps usher in a new era of personalized medicine for women with this difficult-to-treat cancer.”
Approximately 65 months (more than five years) after starting the trial, 28.3% of patients who received Lynparza had not needed additional treatment, a higher percentage than seen in the placebo group (12.8%).
Women who took Lynparza as a maintenance therapy until their disease worsened also had a 26% reduced risk of death. In addition, 38.4% of patients who started in the placebo group crossed over to treatment with Lynparza.
“This study confirms that the PARP inhibitor olaparib [Lynparza] 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,” said Richard L. Schilsky, MD, ASCO chief medical officer and executive vice president at ASCO.
AEs led to dose interruption in 50% of patients in the Lynparza group and 19% of women on a placebo. Dose reductions due to AEs also were needed in 28% of patients in the Lynparza group and 3% in the placebo group. Treatment discontinuation due to AEs was recorded in 17% of women taking Lynparza and 3% of participants receiving a placebo.
Earlier data at approximately 22 months of follow-up had shown that Lynparza extended the time without disease worsening from a median of 5.5 months (with placebo) to 19.1 months, representing a 70% reduction in the risk of disease progression.
Prior results also showed that Lynparza did not have negative effects on the patients’ health-related quality of life. In fact, data suggested that women taking Lynparza fared better and went longer without significant symptoms of toxicity.
Lynparza is already available as a first-line maintenance treatment for women with BRCA-mutated advanced ovarian cancer who responded to initial platinum-based chemotherapy in the U.S. European Union, Canada, Brazil, China, and Japan.
Regulatory approvals were based on the ongoing SOLO-1 Phase 3 trial (NCT01844986), which seeks to assess whether Lynparza extends the time women live without ovarian cancer progression.
After a median follow-up of 41 months, 60% of women taking Lynparza in SOLO-1 were alive and without signs of cancer recurrence or progression, compared with 27% of participants receiving a placebo.