In the phase III SOLO3 trial reported in the Journal of Clinical Oncology, Richard T. Penson, MD, and colleagues found that olaparib was associated with an improved objective response rate and progression-free survival vs nonplatinum chemotherapy in women with platinum-sensitive relapsed ovarian cancer and a germline BRCA1/2 mutation who had received two prior lines of platinum-based chemotherapy.

Richard T. Penson, MD

Study Details

In the international open-label trial, 266 patients were randomly assigned 2:1 to receive oral olaparib at 300 mg twice daily (n = 178) or investigator’s choice of single-agent nonplatinum chemotherapy (n = 88; pegylated liposomal doxorubicin, n = 47; paclitaxel, n = 20; gemcitabine, n = 13; and topotecan, n = 8). The primary endpoint was objective response rate in the measurable disease analysis set assessed by blinded independent central review. The key secondary endpoint of progression-free survival was assessed by blinded independent central review in the intent-to-treat population.

Objective Response and Progression-Free Survival

Among 151 patients treated with olaparib and 72 patients treated with chemotherapy with measurable disease, objective response rates were 72.2% vs 51.4% (odds ratio [OR] = 2.53, 95% confidence interval [CI] = 1.40–4.58, P = .002). In the subgroup of 78 vs 24 patients who had received two prior lines of treatment, objective response rates were 84.6% vs 61.5% (OR = 3.44, 95% CI = 1.42–8.54). Median progression-free survival was 13.4 months vs 9.2 months (hazard ratio = 0.62, 95% CI = 0.43–0.91, P = .013).

Adverse Events

The investigators stated that adverse events were consistent with the established safety profiles of olaparib and chemotherapy. The most common adverse events of any grade were nausea, fatigue/asthenia, anemia, vomiting, and diarrhea in the olaparib group, and fatigue/asthenia, palmar-plantar erythrodysesthesia, nausea, neutropenia, and anemia in the chemotherapy group.

The most common grade ≥ 3 adverse events were anemia (21.3%) in the olaparib group and neutropenia (15.8%) and palmar-plantar erythrodysesthesia (11.8%) in the chemotherapy group. Serious adverse events occurred in 23.6% vs 18.4% of patients, with the most common being anemia (2.8%) and vomiting (3.9%).

The investigators concluded, “Olaparib resulted in statistically significant and clinically relevant improvements in [objective response rate and progression-free survival] compared with nonplatinum chemotherapy in patients with germline BRCA-mutated platinum-sensitive relapsed ovarian cancer who had received at least two prior lines of platinum-based chemotherapy.”

Dr. Penson, of Harvard Medical School and Massachusetts General Hospital, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by AstraZeneca as part of an alliance between AstraZeneca and Merck Sharp & Dohme. For full disclosures of the study authors, visit ascopubs.org.