Clinical effectiveness and safety of olaparib in BRCA-mutated, HER2-negative metastatic breast cancer in a real-world setting: final analysis of LUCY
Authors: Balmaña Judith , Fasching Peter A. , Couch Fergus J. , Delaloge Suzette , Labidi-Galy Intidhar , O’Shaughnessy Joyce , Park Yeon Hee , Eisen Andrea F. , You Benoit , Bourgeois Hughes , Gonçalves Anthony , Kemp Zoe , Swampillai Angela , Jankowski Tomasz , Sohn Joo Hyuk , Poddubskaya Elena , Mukhametshina Guzel , Aksoy Sercan , Timcheva Constanta V. , Park-Simon Tjoung-Won , Antón-Torres Antonio , John Ellie , Baria Katherine , Gibson Isabel , Gelmon Karen A. ,   The LUCY investigators,   Bulgaria, Koynova Tatyana , Popov Vasil , Timcheva Constanta , Tomova Antoaneta ,   Canada, Eisen Andrea , Gelmon Karen , Lemieux Julie ,   France, Augereau Paule , Bazan Fernando , Becuwe Célia , Bourgeois Hugues , Chakiba Camille , Chehimi Mohamad , Cheneau Caroline , Dalenc Florence , de Guillebon Eléonore , de La Motte Rouge Thibault , Frenel Jean-Sébastien , Gonçalves Anthony , Grenier Julien , Hardy-Bessard Anne Claire , Lamy Regine , Levy Christelle , Lortholary Alain , Mailliez Audrey , Medioni Jacques , Patsouris Anne , Spaeth Dominique , Teixeira Luis , Tennevet Isabelle , Venat-Bouvet Laurence , Villanueva Cristian , You Benoit ,   Germany, Ettl Johannes , Fasching Peter , Gerber Bernd , Hanusch Claus Alexander , Hoffmann Oliver , Park-Simon Tjoung-Won , Malter Wolfram , Reinisch Mattea , Tio Joke , Wimberger Pauline ,   Hungary, Boer Katalin , Dank Magdolna ,   Italy, Ballestrero Alberto , Bianchini Giampaolo , Biganzoli Laura , Bordonaro Roberto , Cognetti Francesco , Cortesi Enrico , De Laurentiis Michelino , De Placido Sabino , Gianni Luca , Guarneri Valentina , Marchetti Paulo , Montemurro Filippo , Mosconi Anna Maria , Naso Giuseppe , Puglisi Fabio , Santoro Armando , Zamagni Claudio ,   Japan, Iwata Hiroji , Kim Seung-Jin , Nakamura Seigo ,   Korea, Chae Yee Soo , Cho Eun Kyung , Kim Jee Hyun , Im Seock-Ah , Lee Keun Seok , Park Yeon Hee , Sohn Joo Hyuk ,   Poland, Byrski Tomasz , Huzarski Tomasz , Jankowski Tomasz , Kukielka-Budny Bozena , Lacko Aleksandra , Nowecki Zbigniew , Senkus-Konefka Elzbieta , Szoszkiewicz Renata , Tarnawski Rafal ,   Russia, Andabekov Timur , Dvorkin Mikhail , Dvornichenko Viktoria , Moiseenko Fedor , Mukhametshina Guzel , Poddubskaya Elena , Popova Ekaterina , Tarasova Anna , Sakaeva Dina , Shomova Marina , Vats Anna ,   Spain, Adamo Bárbara , Conejero Raquel Andrés , Torres Antonio Antón , Gelpi Judith Balmaña , de Ibarguen Blanca Cantos Sánchez , Jurado Josefina Cruz , Fernández Nieves Díaz , González Alejandro Falcón , Garcia Juan , Santiago Santiago González , Carrasco Fernando Henao , Lorenzo Isabel Lorenzo , Antón Fernando Moreno , García Beatriz Rojas , Beltrán Salomón Menjón , Santisteban Marta , Stradella Agostina ,   Taiwan, Hou Ming-Feng , Huang Chiun-Sheng , Lin Yung-Chang , Tseng Ling-Ming , Wang Hwei-Chung ,   Turkey, Aksoy Sercan , Arslan Cagatay , Artac Mehmet , Aydiner Adnan , Disel Umut , Ozkan Metin , Ozyilkan Ozgur , Sezer Emel Yaman , Yetisyigit Tarkan ,   UK, Armstrong Anne , Barrett Sophie , Borley Annabel , Kemp Zoe , Michie Caroline , Mukesh Mukesh , Perren Timothy , Swampillai Angela ,   USA, Chaudhry Madhu , Young Tammy 
Published: December 2023

Abstract
Purpose
The interim analysis of the phase IIIb LUCY trial demonstrated the clinical effectiveness of olaparib in patients with germline BRCA-mutated (gBRCAm), human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (mBC), with median progression-free survival (PFS) of 8.11 months, which was similar to that in the olaparib arm of the phase III OlympiAD trial (7.03 months). This prespecified analysis provides final overall survival (OS) and safety data.

Methods
The open-label, single-arm LUCY trial of olaparib (300 mg, twice daily) enrolled adults with gBRCAm or somatic BRCA-mutated (sBRCAm), HER2-negative mBC. Patients had previously received a taxane or anthracycline for neoadjuvant/adjuvant or metastatic disease and up to two lines of chemotherapy for mBC.

Results
Of 563 patients screened, 256 (gBRCAm, n = 253; sBRCAm, n = 3) were enrolled. In the gBRCAm cohort, median investigator-assessed PFS (primary endpoint) was 8.18 months and median OS was 24.94 months. Olaparib was clinically effective in all prespecified subgroups: hormone receptor status, previous chemotherapy for mBC, previous platinum-based chemotherapy (including by line of therapy), and previous cyclin-dependent kinase 4/6 inhibitor use. The most frequent treatment-emergent adverse events (TEAEs) were nausea (55.3%) and anemia (39.2%). Few patients (6.3%) discontinued olaparib owing to a TEAE. No deaths associated with AEs occurred during the study treatment or 30-day follow-up.

Conclusion
The LUCY patient population reflects a real-world population in line with the licensed indication of olaparib in mBC. These findings support the clinical effectiveness and safety of olaparib in patients with gBRCAm, HER2-negative mBC.

Clinical trial registration
Clinical trials registration number: NCT03286842