Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer.

Abstract

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 .).

• Authors: Kathleen Moore, Nicoletta Colombo, Giovanni Scambia, Byoung-Gie Kim, Ana Oaknin, Michael Friedlander, Alla Lisyanskaya, Anne Floquet, Alexandra Leary, Gabe S Sonke, Charlie Gourley, Susana Banerjee, Amit Oza, Antonio González-Martín, Carol Aghajanian, William Bradley, Cara Mathews, Joyce Liu, Elizabeth S Lowe, Ralph Bloomfield, Paul DiSilvestro
• Journal: The New England journal of medicine (N Engl J Med) Vol. 379 Issue 26 Pg. 2495-2505 (12 27 2018) ISSN: 1533-4406 [Electronic] United States
• PMID: 30345884 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Phthalazines
• Piperazines
• Poly(ADP-ribose) Polymerase Inhibitors
• olaparib

Topics

• Adult
• Antineoplastic Agents (therapeutic use)
• Carcinoma, Endometrioid (drug therapy, surgery)
• Combined Modality Therapy
• Double-Blind Method
• Fallopian Tube Neoplasms (drug therapy, surgery)
• Female
• Genes, BRCA1
• Genes, BRCA2
• Germ-Line Mutation
• Humans
• Kaplan-Meier Estimate
• Maintenance Chemotherapy
• Middle Aged
• Ovarian Neoplasms (drug therapy, genetics, surgery)
• Peritoneal Neoplasms (drug therapy, surgery)
• Phthalazines (adverse effects, therapeutic use)
• Piperazines (adverse effects, therapeutic use)
• Poly(ADP-ribose) Polymerase Inhibitors (adverse effects, therapeutic use)
• Progression-Free Survival