Ovarian cancer patients with BRCA mutations who received Lynparza (olaparib) maintenance treatment after first-line platinum-based chemotherapy lived three years longer without signs of disease worsening than patients who received a placebo, data from a Phase 3 trial shows.
Trial results, “Olaparib maintenance therapy following first-line platinum-based chemotherapy in patients with FIGO stage III–IV ovarian cancer (OC) with a BRCA1/2 mutation (BRCAm): Phase III SOLO1 trial,” were presented by Kathleen Moore, MD, on Oct. 21 at the European Society of Medical Oncology (ESMO) 2018 Congress in Munich.
Findings were also published in the study, “Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer,” in The New England Journal of Medicine on the same day.
“The median PFS for patients who received placebo was only 13.8 months while the median PFS for those who received olaparib was not reached but looks to be approximately three years longer than the placebo group,” Moore, who is an associate professor at the Stephenson Cancer Center, University of Oklahoma, said in a press release.
Lynparza acts by preventing cells from repairing their DNA errors. Because cancer cells divide at a faster pace, they accumulate errors faster than healthy cells, leading to their death. Lynparza is particularly effective in cancers with mutations in other DNA-repairing genes, such as BRCA1 and BRCA2.
The therapy is approved for women with BRCA-mutated, advanced ovarian cancer who received at least three prior chemotherapy treatments. It is also indicated as a maintenance treatment for women with BRCA-mutated relapsed ovarian cancer whose tumors responded to platinum-based chemotherapy.
The Phase 3 SOLO-1 trial (NCT01844986) was designed to determine if Lynparza could prevent ovarian cancer from returning or worsening in women who had a complete or partial response to their first-line chemotherapy.
It included 391 patients with high-grade serous or endometrioid ovarian cancer, primarily peritoneal cancer or fallopian-tube cancer (or a combination thereof) with a mutation in BRCA1, BRCA2, or both (BRCA1/2). Of these patients, 388 had a germline BRCA1/2 mutation, while two had a somatic (meaning spontaneous or non-inherited) BRCA1/2 mutation.
This trial “provides the first large dataset of prospectively collected outcomes for this population of women,” Moore said.
Participants were randomly assigned Lynparza (260 patients) or a placebo (131 patients), given twice daily for two years or until disease progression.
The study’s primary objective was progression-free survival, or the time patients lived without disease progression. Secondary objectives included time from randomization to second progression event, overall survival, and quality of life.
After a median follow-up of almost 3.5 years, Lynparza reduced the risk of disease progression or death by 70%. Patients receiving a placebo experienced disease progression or death after a median of 13.8 months, while more than half of patients in the Lynparza group were still alive and disease-free.
Among patients who progressed and received a second treatment course, Lynparza was associated with a 50% lower risk of progression or death after the second treatment.
The therapy was well-tolerated, with the most common serious adverse event being anemia and low neutrophil levels. Researchers also reported there was no clinically meaningful change in the participants’ quality of life.
Adverse events were largely managed by dose interruption or dose reduction, rather than discontinuing the treatment. The discontinuation rate was 12%, all of which were due to drug toxicity, not disease progression.
“While it is too early to say whether we have impacted the fraction of women who could be cured with their front-line therapy, the fact that it is estimated that over 50% of women on the olaparib arm were still progression free at four years as compared to only 11% for placebo speaks to this hope,” Moore said.
“The results of SOLO-1 herald a new era in treatment for women diagnosed with advanced ovarian cancer who carry a BRCA mutation. This study demonstrates an outstanding improvement in PFS over placebo which is maintained even after the olaparib is stopped at two years,” she said.
“These are outstanding results in a worsening disease setting. Not only was olaparib efficacious but it was also shown to be well tolerated,” said Isabelle Ray-Coquard, MD, PhD, a professor at the Université Claude Bernard Lyon 1 in France. “The findings promise to change practice in this subgroup of patients with a BRCA mutation.”