Treatment with Lynparza in the maintenance setting extended overall survival by more than a year in women with platinum-sensitive relapsed ovarian cancer with BRCA1/2 mutations.
Lynparza (olaparib) in the maintenance setting extended overall survival by 12.9 months in women with platinum-sensitive relapsed ovarian cancer with BRCA1/2 mutations, compared with placebo, according to randomized phase 3 trial results presented during a 2020 ASCO Virtual Scientific Program press briefing.
This is the first phase 3 trial to provide overall survival data on a maintenance PARP inhibitor.
“Relapsed ovarian cancer is associated with poor outcomes. Therefore, treatment goals include delaying symptomatic disease progression and prolonging survival,” lead study author Andres Poveda, MD, Initia Oncology, Hospital Quironsalud, in Valencia, Spain, said during a pre-recorded presentation. “However, improvements in overall survival are difficult to demonstrate in ovarian cancer trials because of crossover and limited options. Limited progress has been made in improving overall survival in the last two decades.”
Therefore, the researchers evaluated Lynparza compared with placebo as maintenance treatment in patients with relapsed BRCA-positive ovarian cancer responding to platinum-based chemotherapy who previously received at least two lines of chemotherapy and had cancer that was responding to recent platinum-based chemotherapy.
The primary end point of the study was investigator-assessed progression-free survival (the time from treatment to disease progression). At a median follow-up of 22.1 months, the initial analysis of the trial previously demonstrated that maintenance therapy with the PARP inhibitor induced a statistically significant improvement in median progression-free survival, compared with placebo (19.1 months versus 5.5 months).
“(The PFS results) were the basis for FDA approval of olaparib in this patient population for maintenance therapy. (The OS results), while they won’t change access to the drug because it’s already FDA approved, it is comforting to get the survival data showing that in fact the treatment concurs with progression-free survival benefit,” Richard L. Schilsky, MD, FASP, FSCT, FASCO, ASCO chief medical officer and executive vice president, said during the briefing. In the updated analysis of the trial, Poveda presented on the overall survival associated with the drug.
At final data cut-off on Feb. 3, 2020, median follow-up was 65 months in both treatment arms.
In the final analysis of the double-blind, multicenter SOLO2 trial, median overall survival among the entire cohort was 51.7 months with the PARP inhibitor, compared with 38.8 months with placebo. Those in the BRCA1- or BRCA2­-mutant positive subset demonstrated a median overall survival of 52.4 months with olaparib, compared with 37.4 months with placebo.
At 5 years, 42.1% of women treated with olaparib were alive, compared with 33.2% of those who received placebo.
“A median overall survival improvement of nearly 13 months is impressive in ovarian cancer and brings a substantial benefit to our patients,” Poveda said in a press release. “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.”
Long-term tolerability of the agent appeared to be consistent with previously reported findings. The most common treatment-related side effects were nausea, fatigue. and anemia. Side effects led to dose interruptions in 50% of the olaparib arm and 19% of the placebo arm; dose reductions in 28% and 3%, respectively; and treatment discontinuations in 17% and 3%.
“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,” Schilsky said in the press release.
In an interview with CURE®, Dr. Konstantin Zakashansky, director of minimally invasive surgery for the Mount Sinai Health System and director of gynecologic oncology at Mount Sinai West, applauded the findings.
“This is of the largest improvement in (overall survival) of any recurrent ovarian cancer patients’ trials reported to date,” he said. “PARP inhibitor trials have revolutionized therapy for ovarian cancer in frontline as well as in the recurrent setting. All of the recently presented trials show significant improvement in progression free survival. Overall survival data, however — which is considered the most clinically relevant endpoint in oncology trials and remains the ‘gold standard’ because of its relevance and objectivity – has been limited.”