Universität zu Köln

Tutt, Andrew N. J., Garber, Judy E., Kaufman, Bella, Viale, Giuseppe, Fumagalli, Debora, Rastogi, Priya, Gelber, Richard D., de Azambuja, Evandro ORCID: 0000-0001-9501-4509, Fielding, Anitra, Balmana, Judith, Domchek, Susan M., Gelmon, Karen A., Hollingsworth, Simon J., Korde, Larissa A., Linderholm, Barbro, Bandos, Hanna, Senkus, E., Suga, Jennifer M., Shao, Z., Pippas, Andrew W., Nowecki, Zbigniew, Huzarski, Tomasz, Ganz, Patricia A., Lucas, Peter C., Baker, Nigel, Loibl, Sibylle, McConnell, Robin, Piccart, Martine, Schmutzler, Rita, Steger, Guenther G., Costantino, Joseph P., Arahmani, Amal, Wolmark, Norman, McFadden, Eleanor, Karantza, Vassiliki, Lakhani, Sunil R., Yothers, Greg ORCID: 0000-0002-7965-7333, Campbell, Christine and Geyer, Charles E. (2021). Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer. N. Engl. J. Med., 384 (25). S. 2394 - 2406. WALTHAM: MASSACHUSETTS MEDICAL SOC. ISSN 1533-4406

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Abstract

BACKGROUND Poly(adenosine diphosphate-ribose) polymerase inhibitors target cancers with defects in homologous recombination repair by synthetic lethality. New therapies are needed to reduce recurrence in patients with BRCA1 or BRCA2 germline mutation-associated early breast cancer. METHODS We conducted a phase 3, double-blind, randomized trial involving patients with human epidermal growth factor receptor 2 (HER2)-negative early breast cancer with BRCA1 or BRCA2 germline pathogenic or likely pathogenic variants and high-risk clinicopathological factors who had received local treatment and neoadjuvant or adjuvant chemotherapy. Patients were randomly assigned (in a 1:1 ratio) to 1 year of oral olaparib or placebo. The primary end point was invasive disease-free survival. RESULTS A total of 1836 patients underwent randomization. At a prespecified event-driven interim analysis with a median follow-up of 2.5 years, the 3-year invasive disease-free survival was 85.9% in the olaparib group and 77.1% in the placebo group (difference, 8.8 percentage points; 95% confidence interval [CI], 4.5 to 13.0; hazard ratio for invasive disease or death, 0.58; 99.5% CI, 0.41 to 0.82; P<0.001). The 3-year distant disease-free survival was 87.5% in the olaparib group and 80.4% in the placebo group (difference, 7.1 percentage points; 95% CI, 3.0 to 11.1; hazard ratio for distant disease or death, 0.57; 99.5% CI, 0.39 to 0.83; P<0.001). Olaparib was associated with fewer deaths than placebo (59 and 86, respectively) (hazard ratio, 0.68; 99% CI, 0.44 to 1.05; P=0.02); however, the between-group difference was not significant at an interim-analysis boundary of a P value of less than 0.01. Safety data were consistent with known side effects of olaparib, with no excess serious adverse events or adverse events of special interest. CONCLUSIONS Among patients with high-risk, HER2-negative early breast cancer and germline BRCA1 or BRCA2 pathogenic or likely pathogenic variants, adjuvant olaparib after completion of local treatment and neoadjuvant or adjuvant chemotherapy was associated with significantly longer survival free of invasive or distant disease than was placebo. Olaparib had limited effects on global patient-reported quality of life.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Tutt, Andrew N. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Garber, Judy E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kaufman, Bella UNSPECIFIED UNSPECIFIED UNSPECIFIED Viale, Giuseppe UNSPECIFIED UNSPECIFIED UNSPECIFIED Fumagalli, Debora UNSPECIFIED UNSPECIFIED UNSPECIFIED Rastogi, Priya UNSPECIFIED UNSPECIFIED UNSPECIFIED Gelber, Richard D. UNSPECIFIED UNSPECIFIED UNSPECIFIED de Azambuja, Evandro UNSPECIFIED orcid.org/0000-0001-9501-4509 UNSPECIFIED Fielding, Anitra UNSPECIFIED UNSPECIFIED UNSPECIFIED Balmana, Judith UNSPECIFIED UNSPECIFIED UNSPECIFIED Domchek, Susan M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gelmon, Karen A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hollingsworth, Simon J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Korde, Larissa A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Linderholm, Barbro UNSPECIFIED UNSPECIFIED UNSPECIFIED Bandos, Hanna UNSPECIFIED UNSPECIFIED UNSPECIFIED Senkus, E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Suga, Jennifer M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Shao, Z. UNSPECIFIED UNSPECIFIED UNSPECIFIED Pippas, Andrew W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Nowecki, Zbigniew UNSPECIFIED UNSPECIFIED UNSPECIFIED Huzarski, Tomasz UNSPECIFIED UNSPECIFIED UNSPECIFIED Ganz, Patricia A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lucas, Peter C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Baker, Nigel UNSPECIFIED UNSPECIFIED UNSPECIFIED Loibl, Sibylle UNSPECIFIED UNSPECIFIED UNSPECIFIED McConnell, Robin UNSPECIFIED UNSPECIFIED UNSPECIFIED Piccart, Martine UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmutzler, Rita UNSPECIFIED UNSPECIFIED UNSPECIFIED Steger, Guenther G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Costantino, Joseph P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Arahmani, Amal UNSPECIFIED UNSPECIFIED UNSPECIFIED Wolmark, Norman UNSPECIFIED UNSPECIFIED UNSPECIFIED McFadden, Eleanor UNSPECIFIED UNSPECIFIED UNSPECIFIED Karantza, Vassiliki UNSPECIFIED UNSPECIFIED UNSPECIFIED Lakhani, Sunil R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Yothers, Greg UNSPECIFIED orcid.org/0000-0002-7965-7333 UNSPECIFIED Campbell, Christine UNSPECIFIED UNSPECIFIED UNSPECIFIED Geyer, Charles E. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-607853
DOI:	10.1056/NEJMoa2105215
Journal or Publication Title:	N. Engl. J. Med.
Volume:	384
Number:	25
Page Range:	S. 2394 - 2406
Date:	2021
Publisher:	MASSACHUSETTS MEDICAL SOC
Place of Publication:	WALTHAM
ISSN:	1533-4406
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DNA-REPAIR DEFECT; MUTANT-CELLS; MUTATION; SURVIVAL; PATHOLOGY; OVARIAN; TUMORS Multiple languages Medicine, General & Internal Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/60785