BACKGROUND
Olaparib is an oral poly(adenosine diphosphate-ribose) polymerase inhibitor that has promising antitumor activity in patients with metastatic breast cancer and a germline BRCA mutation.
METHODS
We conducted a randomized, open-label, phase 3 trial in which olaparib monotherapy was compared with standard therapy in patients with a germline BRCA mutation and human epidermal growth factor receptor type 2 (HER2)-negative metastatic breast cancer who had received no more than two previous chemotherapy regimens for metastatic disease. Patients were randomly assigned, in a 2: 1 ratio, to receive olaparib tablets (300 mg twice daily) or standard therapy with single-agent chemotherapy of the physician's choice (capecitabine, eribulin, or vinorelbine in 21-day cycles). The primary end point was progression-free survival, which was assessed by blinded independent central review and was analyzed on an intention-to-treat basis.
RESULTS
Of the 302 patients who underwent randomization, 205 were assigned to receive olaparib and 97 were assigned to receive standard therapy. Median progression-free survival was significantly longer in the olaparib group than in the standardtherapy group (7.0 months vs. 4.2 months; hazard ratio for disease progression or death, 0.58; 95% confidence interval, 0.43 to 0.80; P<0.001). The response rate was 59.9% in the olaparib group and 28.8% in the standard-therapy group. The rate of grade 3 or higher adverse events was 36.6% in the olaparib group and 50.5% in the standard-therapy group, and the rate of treatment discontinuation due to toxic effects was 4.9% and 7.7%, respectively.
CONCLUSIONS
Among patients with HER2-negative metastatic breast cancer and a germline BRCA mutation, olaparib monotherapy provided a significant benefit over standard therapy; median progression-free survival was 2.8 months longer and the risk of disease progression or death was 42% lower with olaparib monotherapy than with standard therapy. (Funded by AstraZeneca; OlympiAD ClinicalTrials.gov number, NCT02000622.)
[1]Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA.
[2]Seoul Natl Univ, Coll Med, Seoul Natl Univ Hosp, Canc Res Inst, Seoul, South Korea.
[3]Med Univ Gdansk, Gdansk, Poland.
[4]Chinese Acad Med Sci, Natl Canc Ctr, Canc Hosp, Beijing, Peoples R China.
[5]Peking Union Med Coll, Beijing, Peoples R China.
[6]Jilin Univ, Hosp 1, Changchun, Jilin, Peoples R China.
[7]Univ Penn, Basser Ctr, Philadelphia, PA 19104 USA.
[8]Natl Hosp Org, Osaka Natl Hosp, Osaka, Japan.
[9]Inst Gustave Roussy, Villejuif, France.
[10]Dana Farber Harvard Canc Ctr, Beth Israel Deaconess Med Ctr, Boston, MA USA.
[11]Univ Manchester, Christie Hosp NHS Fdn Trust, Manchester, Lancs, England.
[12]Univ Manchester, Fac Biol Med & Hlth, Manchester, Lancs, England.
[13]Astra Zeneca, Macclesfield, Cheshire, England.
[14]Univ Padua, Padua, Italy.
[15]Ist Ricovero & Cura Carattere Sci, Ist Oncol Veneto, Padua, Italy.
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