Treatment with 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.
Treatment with olaparib (Lynparza) in the maintenance setting extended overall survival (OS) 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.1
“A median overall survival improvement of nearly 13 months is impressive in ovarian cancer and brings a substantial benefit to our patients,” lead study author Andres Poveda, MD, Initia Oncology, Hospital Quironsalud, in Valencia, Spain, said in a press release.2
In the final analysis of the double-blind, multicenter SOLO2 trial (ENGOT ov-21; NCT01874353), median OS among the entire cohort was 51.7 months with the PARP inhibitor, compared with 38.8 months with placebo (HR, 0.74; 95% CI, 0.54-1.00; P = 0.0537). Those in the BRCA1- or BRCA2-mutant positive subset demonstrated a median OS of 52.4 months with olaparib, compared with 37.4 months with placebo (HR, 0.71; 95% CI, 0.52-0.97; P = 0.0306).
At 5 years, 42.1% of women treated with olaparib were alive, compared to 33.2% of those who received placebo.
According to a pre-specified sensitivity analysis, median OS was 51.7 months in the olaparib arm, compared with 38.8 months in the placebo arm (HR, 0.70; 95% CI, 0.52-0.96; P = 0.0231).
Of note, the SOLO2 trial is the first phase 3 trial to provide OS data on a maintenance PARP inhibitor, Poveda explained.
“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,” he added in the release.
Poveda noted that 39% of patients in the placebo group crossed over to treatment with olaparib and were not included in the OS analysis. 11% of patients treated with olaparib received a subsequent PARP inhibitor.
Long-term tolerability of the agent appeared to be consistent with previously reported findings. The most common treatment-related adverse events (AEs) were nausea, fatigue, and anemia. AEs 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%.
At final data cut-off on February 3, 2020, median follow-up was 65 months in both treatment arms. The trial included patients with relapsed BRCA-positive ovarian cancer responding to platinum-based chemotherapy who previously received at least 2 lines of chemotherapy and had cancer that was responding to recent platinum-based chemotherapy. Patients were randomized 2:1 to receive maintenance therapy with olaparib as a 300-mg tablet twice daily (n = 196) or placebo (n = 99). Study treatment continued until disease progression.
The primary end point of the study was investigator-assessed progression-free survival (PFS). At a median follow-up of 22.1 months, the trial previously demonstrated that maintenance therapy with the PARP inhibitor induced a statistically significant improvement in median PFS, compared with placebo (19.1 months [95% CI, 16.3-25.7] vs 5.5 months [95% CI, 5.2-5.8]; HR, 0.30; 95% CI, 0.22-0.41; P < .0001).3
“(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.
Moreover, previous results showed that the adjusted average mean change from baseline over the first 12 months in Trial Outcome Index was −2.90 (95% CI, −4.13 to −1.67) with olaparib, compared with −2.87 (95% CI, –4.64 to −1.10) with placebo (95% CI, −2.19 to 2.13; P = 0.98); and mean quality-adjusted progression-free survival (13.96 months [SD, 10.96] vs 7.28 [SD, 5.22] months, respectively; 95% CI, 4.98-8.54) and mean duration of time without significant symptoms of toxicity (15.03 months [SD, 12.79] vs 7.70 months [SD, 6.42] months; 95% CI, 4.70-8.96) were also significantly longer with the PARP inhibitor.4
“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.