Overall survival in the OlympiA phase Ill trial of adjuvant olaparib in patients with germime pathogenic variants in BRCA1/2 and high-risk, early breast cancer

被引：268

作者：

Geyer, C. E., Jr. ^{[1
,2
]}

Garber, J. E. ^{[3
]}

Gelber, R. D. ^{[3
,4
,5
]}

Yothers, G. ^{[1
,6
]}

Taboada, M. ^{[7
]}

Ross, L. ^{[8
]}

Rastogi, P. ^{[1
,2
]}

Cui, K. ^{[9
]}

Arahmani, A. ^{[10
]}

Aktan, G. ^{[11
]}

Armstrong, A. C. ^{[12
]}

Arnedos, M. ^{[13
,14
]}

Balmana, J. ^{[15
,16
]}

Bergh, J. ^{[17
,18
,19
]}

Bliss, J. ^{[20
,21
]}

Delaloge, S. ^{[22
,23
]}

Domchek, S. M. ^{[24
]}

Eisen, A. ^{[25
]}

Elsafy, F. ^{[7
]}

Fein, L. E. ^{[26
]}

Fielding, A. ^{[9
]}

Ford, J. M. ^{[27
]}

Friedman, S. ^{[28
]}

Gelmon, K. A. ^{[29
]}

Gianni, L. ^{[30
,31
]}

Gnant, M. ^{[32
]}

Hollingsworth, S. J. ^{[33
]}

Im, S-A ^{[34
]}

Jager, A. ^{[35
]}

Lakhani, S. R. ^{[37
]}

Janni, W. ^{[38
]}

Linderholm, B. ^{[39
,40
]}

Liu, T-W ^{[41
]}

Loman, N. ^{[42
]}

Korde, L. ^{[43
]}

Loibl, S. ^{[44
,45
,46
]}

Lucas, P. C. ^{[1
,47
]}

Marme, F. ^{[48
,49
]}

de Duenas, E. Martinez ^{[50
]}

McConnell, R. ^{[8
]}

Phillips, K-A ^{[51
,52
]}

Piccart, M. ^{[53
]}

Rossi, G. ^{[54
]}

Schmutzler, R. ^{[55
,56
]}

Senkus, E. ^{[57
]}

Shao, Z. ^{[58
]}

Sharma, P. ^{[59
]}

Singer, C. F. ^{[32
,60
]}

Spanic, T. ^{[61
,62
]}

Stickeler, E. ^{[63
]}

机构：

[1] NRG Oncol NSABP Fdn, Pittsburgh, PA USA

[2] UPMC Hillman Canc Ctr, Dept Med, Pittsburgh, PA USA

[3] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA 02115 USA

[4] Harvard TH Chan Sch Publ Hlth, Boston, MA USA

[5] Frontier Sci Fdn, Boston, MA USA

[6] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA

[7] AstraZeneca, Oncol Biometr Dept, Macclesfield, Cheshire, England

[8] Frontier Sci Scotland, Dept Data Management, Kincraig, Scotland

[9] AstraZeneca, Dept Oncol R&D, Gaithersburg, MD USA

[10] Breast Int Grp, Res Operat Dept, Brussels, Belgium

[11] Merck & Co Inc, Global Oncol Clin Dev, Rahway, NJ 07065 USA

[12] Christie Hosp NHS Fdn Trust, Dept Med Oncol, Manchester, Lancs, England

[13] European Org Res & Treatment EORTC, Brussels, Belgium

[14] Inst Bergonie, Dept Med Oncol, Bordeaux, France

[15] Vall dHebron Inst Oncol, Med Oncol Dept, Barcelona, Spain

[16] Vall dHebron Univ Hosp, Barcelona, Spain

[17] Karolinska Inst, Dept Oncol Pathol, Swedish Breast Canc Grp, Stockholm, Sweden

[18] Karolinska Univ Hosp, Breast Canc Ctr, Stockholm, Sweden

[19] Karolinska Comprehens Canc Ctr, Stockholm, Sweden

[20] Inst Canc Res, Dept Clin Trials, London, England

[21] Inst Canc Res, Stat Unit ICR CTSU, London, England

[22] Inst Gustave Roussy, Dept Canc Med, Paris, France

[23] Unicanc Breast Grp, Paris, France

[24] Univ Penn, Basser Ctr BRCA, Abramson Canc Ctr, Dept Med, Philadelphia, PA USA

[25] Univ Toronto, Odette Canc Ctr, Dept Med, Toronto, ON, Canada

[26] Inst Oncol Rosario, Dept Clin Res, Santa Fe, Argentina

[27] Stanford Univ, Sch Med, Dept Med Oncol, Stanford, CA 94305 USA

[28] Facing Our Risk Canc Empowered, Tampa, FL USA

[29] BC Canc, Dept Med Oncol, Vancouver, BC, Canada

[30] Int Breast Canc Study Grp, Dept Oncol, Bern, Switzerland

[31] Osped Infermi AUSL Romagna, Dept Med Oncol, Rimini, Italy

[32] Med Univ Vienna, Comprehens Canc Ctr, Vienna, Austria

[33] AstraZeneca, Dept Late Dev Oncol, Cambridge, England

[34] Seoul Natl Univ, Seoul Natl Univ Hosp, Coll Med, Canc Res Inst,Dept Internal Med, Seoul, South Korea

[35] Dutch Breast Canc Res Grp, Dept Med Oncol, Utrecht, Netherlands

[36] Landsp Tali Univ Hosp Iceland, Dept Med Oncol, Iceland Breast Canc Grp, Reykjavik, Iceland

[37] Univ Queensland, Ctr Clin Res & Pathol Queensland, Dept Anat Pathol, Brisbane, Qld, Australia

[38] Univ Ulm, Univ Klinikum, Dept Obstet & Gynecol, Ulm, Germany

[39] Sahlgrens Univ Hosp, Dept Oncol, Gothenburg, Sweden

[40] Gothenburg Univ, Sahlgrenska Acad, Inst Clin Sci, Dept Oncol, Gothenburg, Sweden

[41] Natl Hlth Res Inst, Div Canc Res, Taiwan Cooperat Oncol Grp, Taipei, Taiwan

[42] Skane Univ Hosp, Dept Hematol Oncol & Radiat Phys, Swedish Assoc Breast Oncologists, Lund, Sweden

[43] NCI, Clin Invest Branch, Div Canc Treatment & Diag, Rockville, MD USA

[44] German Breast Grp, Med & Res, Neu Isenburg, Germany

[45] Ctr Hematol & Oncol Bethanien, Med & Res, Frankfurt, Germany

[46] Goethe Univ, Frankfurt, Germany

[47] UPMC Hillman Canc Ctr, Dept Pathol, Pittsburgh, PA USA

[48] Heidelberg Univ, Med Fac Mannheim, Mannheim, Germany

[49] German Breast Grp, Neu Isenburg, Germany

[50] Med Consorcio Hosp Prov Castellon, Serv Oncol, Castellon de La Plana, Spain

来源：

ANNALS OF ONCOLOGY | 2022年 / 33卷 / 12期

基金：

美国国家卫生研究院;

关键词：

breast cancer; BRCA1/2; PARP inhibition; olaparib; adjuvant therapy; DNA-REPAIR DEFECT; MUTATION CARRIERS; STAGING SYSTEM; MUTANT-CELLS; CAPECITABINE; CHEMOTHERAPY;

D O I：

10.1016/j.annonc.2022.09.159

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: The randomized, double-blind OlympiA trial compared 1 year of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS). The olaparib group had fewer deaths than the placebo group, but the difference did not reach statistical significance for overall survival (OS). We now report the pre-specified second IA of OS with updates of IDFS, DDFS, and safety. Patients and methods: One thousand eight hundred and thirty-six patients were randomly assigned to olaparib or placebo following (neo)adjuvant chemotherapy, surgery, and radiation therapy if indicated. Endocrine therapy was given concurrently with study medication for hormone receptor-positive cancers. Statistical significance for OS at this IA required P < 0.015. Results: With a median follow-up of 3.5 years, the second IA of OS demonstrated significant improvement in the olaparib group relative to the placebo group [hazard ratio 0.68; 98.5% confidence interval (CI) 0.47-0.97; P = 0.009]. Four-year OS was 89.8% in the olaparib group and 86.4% in the placebo group (Delta 3.4%, 95% CI -0.1% to 6.8%). Four-year IDFS for the olaparib group versus placebo group was 82.7% versus 75.4% (Delta 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Delta 7.4%, 95% CI 3.6% to 11.3%), respectively. Subset analyses for OS, IDFS, and DDFS demonstrated benefit across major subgroups. No new safety signals were identified including no new cases of acute myeloid leukemia or myelodysplastic syndrome. Conclusion: With 35 years of median follow-up, OlympiA demonstrates statistically significant improvement in OS with adjuvant olaparib compared with placebo for gBRCA1/2pv-associated EBC and maintained improvements in the previously reported, statistically significant endpoints of IDES and DDFS with no new safety signals.

引用

页码：1250 / 1268

页数：19

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