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.
Lynparza’s long-term tolerability profile of Lynparza was generally consistent with previous reports, with the most common adverse events (AEs, side effects) being nausea, fatigue, and anemia.
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.