PURPOSE: A phase II study (ClinicalTrials.gov identifier: NCT00628251) showed activity of olaparib capsules versus pegylated liposomal doxorubicin in patients with germline BRCA-mutated platinum-resistant or partially platinum-sensitive relapsed ovarian cancer. We conducted a phase III trial (SOLO3) of olaparib tablets versus nonplatinum chemotherapy in patients with germline BRCA-mutated platinum-sensitive relapsed ovarian cancer who had received at least 2 prior lines of platinum-based chemotherapy. PATIENTS AND METHODS: In this randomized, open-label trial, patients were randomly assigned 2:1 to olaparib 300 mg twice a day or physician's choice single-agent nonplatinum chemotherapy (pegylated liposomal doxorubicin, paclitaxel, gemcitabine, or topotecan). The primary end point was objective response rate (ORR) in the measurable disease analysis set assessed by blinded independent central review (BICR). The key secondary end point was progression-free survival (PFS) assessed by BICR in the intent-to-treat population. RESULTS: Of 266 randomly assigned patients, 178 were assigned to olaparib and 88 to chemotherapy. In patients with measurable disease (olaparib, n = 151; chemotherapy, n = 72), the BICR-assessed ORR was significantly higher with olaparib than with chemotherapy (72.2% v 51.4%; odds ratio [OR], 2.53 [95% CI, 1.40 to 4.58]; P = .002). In the subgroup who had received 2 prior lines of treatment, the ORR was 84.6% with olaparib and 61.5% with chemotherapy (OR, 3.44 [95% CI, 1.42 to 8.54]). BICR-assessed PFS also significantly favored olaparib versus chemotherapy (hazard ratio, 0.62 [95% CI, 0.43 to 0.91]; P = .013; median, 13.4 v 9.2 months). Adverse events were consistent with the established safety profiles of olaparib and chemotherapy. CONCLUSION: Olaparib resulted in statistically significant and clinically relevant improvements in ORR and PFS compared with nonplatinum chemotherapy in patients with germline BRCA-mutated platinum-sensitive relapsed ovarian cancer who had received at least 2 prior lines of platinum-based chemotherapy.

1st Faculty of Medicine Charles University and General University Prague Czech Republic

Asan Medical Center Seoul South Korea

AstraZeneca Cambridge United Kingdom

AstraZeneca Gaithersburg MD

Centro Medico Dalinde Mexico City Mexico

Faculty of Medicine and Health Sciences Jan Kochanowski University Kielce Poland

Harvard Medical School and Massachusetts General Hospital Boston MA

Instituto COI de Educação e Pesquisa Rio de Janeiro Brazil

Korea Institute of Radiological and Medical Sciences Seoul South Korea

Medical University K Marcinkowski and Clinical Hospital of the Transfiguration Poznań Poland

Oaxaca Site Management Organization Oaxaca de Juarez Mexico

Seoul National University Hospital Seoul South Korea

Università Cattolica del Sacro Cuore Fondazione Policlinico A Gemelli IRCCS Rome Italy

University of Alabama Birmingham AL

University of Milan Bicocca and IEO European Institute of Oncology IRCCS Milan Italy

J Clin Oncol. 2020 Aug 10;38(23):2698. doi: 10.1200/JCO.20.01235. PubMed

J Clin Oncol. 2020 Aug 10;38(23):2697-2698. doi: 10.1200/JCO.20.00576. PubMed

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ClinicalTrials.gov
NCT00628251, NCT02282020