Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer
Open accessAbstract
BACKGROUND: Most women with newly diagnosed advanced ovarian cancer have a relapse within 3 years after standard treatment with surgery and platinum-based chemotherapy. The benefit of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor olaparib in relapsed disease has been well established, but the benefit of olaparib as maintenance therapy in newly diagnosed disease is uncertain. METHODS: We conducted an international, randomized, double-blind, phase 3 trial to evaluate the efficacy of olaparib as maintenance therapy in patients with newly diagnosed advanced (International Federation of Gynecology and Obstetrics stage III or IV) high-grade serous or endometrioid ovarian cancer, primary peritoneal cancer, or fallopian-tube cancer (or a combination thereof) with a mutation in BRCA1, BRCA2, or both ( BRCA1/2) who had a complete or partial clinical response after platinum-based chemotherapy. The patients were randomly assigned, in a 2:1 ratio, to receive olaparib tablets (300 mg twice daily) or placebo. The primary end point was progression-free survival. RESULTS: Of the 391 patients who underwent randomization, 260 were assigned to receive olaparib and 131 to receive placebo. A total of 388 patients had a centrally confirmed germline BRCA1/2 mutation, and 2 patients had a centrally confirmed somatic BRCA1/2 mutation. After a median follow-up of 41 months, the risk of disease progression or death was 70% lower with olaparib than with placebo (Kaplan-Meier estimate of the rate of freedom from disease progression and from death at 3 years, 60% vs. 27%; hazard ratio for disease progression or death, 0.30; 95% confidence interval, 0.23 to 0.41; P<0.001). Adverse events were consistent with the known toxic effects of olaparib. CONCLUSIONS: The use of maintenance therapy with olaparib provided a substantial benefit with regard to progression-free survival among women with newly diagnosed advanced ovarian cancer and a BRCA1/2 mutation, with a 70% lower risk of disease progression or death with olaparib than with placebo. (Funded by AstraZeneca and Merck; SOLO1 ClinicalTrials.gov number, NCT01844986 .).
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Olaparib has shown substantial efficacy in various cancers, including ovarian, breast, and PCa.
“Olaparib, has shown substantial efficacy in various cancers, including ovarian, breast, and PCa [26–28].”
From Celastrol attenuates the invasion and migration and augments the anticancer effects of olaparib in prostate cancer (2024) · cites this paper as [26]
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“Finally, although nausea, fatigue and vomiting were observed in 50% or more of patients, these toxicities were mostly grade 1 and 2, easily manageable, and comparable to those observed with olaparib monotherapy (77% nausea, 63% fatigue and 40% vomiting in the recently reported SOLO1 study(22)).”
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“Olaparib, has shown substantial efficacy in various cancers, including ovarian, breast, and PCa [26–28].”
BackgroundPoly(ADP-Ribose) Polymerase Inhibitor Inhibition in Ovarian Cancer: A Comprehensive Review
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- Authors
- Moore, K., Colombo, N., Scambia, G., Kim, B.-G., Oaknin, A., Friedlander, M., Lisyanskaya, A., Floquet, A., Leary, A., Sonke, G. S., Gourley, C., Banerjee, S., Oza, A., González-Martín, A., Aghajanian, C., Bradley, W., Mathews, C., Liu, J., Lowe, E. S., Bloomfield, R., & DiSilvestro, P.
- Affiliations
- Università Cattolica del Sacro Cuore (IT)
- From the Stephenson Cancer Center at the University of Oklahoma, Oklahoma City (K.M.); University of Milan–Bicocca, European Institute of Oncology Istituto di Ricovero e Cura a Carattere Scientifico, Milan (N.C.), and Fondazione Policlinico Universitario A. Gemelli IRCCS Università Cattolica, Rome (G.S.) — both in Italy; Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea (B.-G.K.); Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology, Barcelona ...
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2018-12-27
- Volume
- 379
- Issue
- 26
- Pages
- 2495-2505
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2897430921
- Cited by
- 2,870
- References
- 1
- Citations by year
- 2026: 268 · 2025: 318 · 2024: 356 · 2023: 400 · 2022: 423 · 2021: 450 · 2020: 408 · 2019: 225 · 2018: 16 · 2017: 1 · 2013: 1
- FWCI
- 103.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- BOA (University of Milano-Bicocca) (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Funders
- AstraZeneca
- Topics
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Health Sciences › Medicine › Reproductive Medicine › Ovarian cancer diagnosis and treatment
- Keywords
- olaparib, maintenance therapy, PARP inhibitors, BRCA1 mutation, BRCA2 mutation, high-grade serous ovarian cancer, endometrioid ovarian cancer, fallopian tube cancer, primary peritoneal cancer, progression-free survival, platinum-based chemotherapy
- MeSH terms
- Poly(ADP-ribose) Polymerase Inhibitors, Progression-Free Survival, Adult, Antineoplastic Agents, Combined Modality Therapy, Double-Blind Method, Fallopian Tube Neoplasms, Female, Humans, Middle Aged, Ovarian Neoplasms, Peritoneal Neoplasms, Phthalazines, Piperazines, Germ-Line Mutation, Carcinoma, Endometrioid, Genes, BRCA1, Genes, BRCA2, Kaplan-Meier Estimate, Maintenance Chemotherapy
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