Maintenance Olaparib Reduces Risk of Progression or Death by 70% in Ovarian Cancer, Phase III Data Shows


The risk of progression or death was reduced by 70% with maintenance olaparib (Lynparza) compared with placebo for patients with platinum-sensitive, relapsed, <em>BRCA</em>-mutant ovarian cancer.

Eric Pujade-Lauraine, MD, PhD

Eric Pujade-Lauraine, MD, PhD

The risk of progression or death was reduced by 70% with maintenance olaparib (Lynparza) compared with placebo for patients with platinum-sensitive, relapsed,BRCA-mutant ovarian cancer, according to results from the phase III SOLO2/ENGOT Ov-21 trial published inThe Lancet Oncology.

Based on data from the SOLO2 trial, the FDA granted a priority review in March to a new drug application for maintenance olaparib. The agency is scheduled to make its final decision on the PARP inhibitor before the end of the year.

&ldquo;Our results confirm that olaparib can achieve a significant prolongation of progression-free survival in this patient population with no appreciable detrimental effect observed for patients&rsquo; quality of life,&rdquo; lead author Eric Pujade-Lauraine, MD, PhD, University of Paris Descartes, and co-investigators wrote. &ldquo;The favorable safety profile in SOLO2 enabled most patients receiving olaparib to maintain full dosing throughout their maintenance treatment.&rdquo;

Between September 2013 and November 2014, investigators recruited 295 women for the international, double-blind, randomized SOLO2/ENGOT Ov-21 trial. Eligible patients had a performance status of 0 or 1, and histologically confirmed, relapsed, high-grade serous ovarian cancer or high-grade endometrioid cancer, including primary peritoneal or fallopian tube cancer.

Patients were required to have a predicted deleterious, or suspected deleteriousBRCA1/2mutation based on either blood or tumor testing, and all patients had to consent to provide 2 blood samples for confirmatory germlineBRCA1/2mutation testing. Overall, 78% of patients assigned to olaparib and 84% of those assigned to placebo had a BRCA1/2 mutation previously determined by local testing. All patients received a confirmatoryBRCAtest as part of the trial, which confirmed a germlineBRCA1/2mutation in 97% of both arms.

Patients were randomly assigned in a 2:1 ratio to 300 mg of olaparib twice daily (n = 196) or placebo (n = 99). Treatment continued until disease progression or until the investigator deemed that a patient was no longer benefiting from treatment. PFS was the primary endpoint.

Overall, 86 patients assigned to placebo discontinued the study, including 76 due to progression and 2 due to toxicity. A total of 112 patients in the experimental arm discontinued, including 75 due to progression and 22 due to toxicity. Eighty-three patients in the experimental group and 13 in the control group remained on-study at the September 19, 2016, data cutoff.

Investigators performed efficacy analysis after 187 deaths or progression events. Median follow-up for PFS was 22.1 months in the olaparib group and 22.2 months with placebo.

Progression-free survival was 19.1 months for the olaparib arm compared with 5.5 months for the placebo group (hazard ratio [HR], 0.30; 95% CI, 0.22-0.41;P<.0001).

According to the Kaplan-Meier survival estimator, 12-month PFS was 65% (95% CI, 57.8-71.4) in the olaparib group versus 21% (95% CI, 13.3-29.6) in the placebo group. PFS also favored olaparib at 24 months (43% vs 15%).

For patients with confirmed or suspected deleteriousBRCA1/2mutations (n = 286), PFS was, again, superior for olaparib compared with placebo (19.3 vs 5.5 months; HR, 0.33; 95% CI, 0.24-0.44;P<.0001).

The investigators reported that the incidence of grade &ge;3 adverse events (AEs) was low in both groups. Thirty-five patients (18%) in the olaparib group experienced serious AEs compared with eight (8%) patients in the placebo group. The most common serious AEs in the olaparib group were anemia (4%), abdominal pain (2%), and intestinal obstruction (2%). The most common serious AEs in the placebo group were constipation (2%) and intestinal obstruction (2%).

A total of 45 patients (23%) in the olaparib group died during the study, including 1 patient who died of grade 5 acute myeloid leukemia. Twenty-seven (27%) patients died in the placebo arm.

Four patients in the both groups experienced acute myeloid leukemia, myelodysplastic syndrome, and/or chronic myelomonocytic leukemia during the study and long-term follow-up. Overall, the incidence of all secondary malignancies during the study and long-term follow-up was 6 patients (3%) in the olaparib group and 5 patients (5%) in the placebo group.


Pujade-Lauraine E, Ledermann JA, Selle F, et al. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial [published online July 25].Lancet Oncol.doi: 10.1016/S1470-2045(17)30469-2.

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