Clinical effectiveness of olaparib monotherapy in germline BRCA-mutated, HER2-negative metastatic breast cancer in a real-world setting: phase IIIb LUCY interim analysis
Karen A Gelmon, Peter A Fasching, Fergus J Couch, Judith Balmaña, Suzette Delaloge, Intidhar Labidi-Galy, James Bennett, Susan McCutcheon, Graham Walker, Joyce O'Shaughnessy, Collaborating Investigators, Constanta Timcheva, Antoaneta Tomova, Andrea Eisen, Karen Gelmon, Julie Lemieux, Fernando Bazan, Hugues Bourgeois, Camille Chakiba, Mohamad Chehimi, Florence Dalenc, Thibault De La Motte Rouge, Jean-Sébastien Frenel, Anthony Gonçalves, Anne Claire Hardy-Bessard, Regine Lamy, Christelle Levy, Alain Lortholary, Audrey Mailliez, Jacques Medioni, Anne Patsouris, Dominique Spaeth, Luis Teixeira, Isabelle Tennevet, Cristian Villanueva, Benoit You, Johannes Ettl, Bernd Gerber, Oliver Hoffmann, Tjoung-Won Park-Simon, Mattea Reinisch, Joke Tio, Pauline Wimberger, Katalin Boer, Alberto Ballestrero, Giampaolo Bianchini, Laura Biganzoli, Roberto Bordonaro, Francesco Cognetti, Michelino De Laurentiis, Sabino De Placido, Valentina Guarneri, Filippo Montemurro, Giuseppe Naso, Armando Santoro, Claudio Zamagni, Seung-Jin Kim, Seigo Nakamura, Yee Soo Chae, Eun Kyung Cho, Kim Jee Hyun, Seock-Ah Im, Keun Seok Lee, Yeon Hee Park, Joo Hyuk Sohn, Tomasz Byrski, Tomasz Huzarski, Bozena Kukielka-Budny, Zbigniew Nowecki, Renata Szoszkiewicz, Rafal Tarnawski, Viktoria Dvornichenko, Fedor Moiseenko, Guzel Mukhametshina, Elena Poddubskaya, Ekaterina Popova, Anna Tarasova, Anna Vats, Bárbara Adamo, Raquel Andrés Conejero, Antonio Antón Torres, Judith Balmaña Gelpi, Nieves Díaz Fernández, Alejandro Falcón González, Juan Garcia, Isabel Lorenzo-Lorenzo, Fernando Moreno Antón, Marta Santisteban, Agostina Stradella, Chiun-Sheng Huang, Sercan Aksoy, Cagatay Arslan, Mehmet Artac, Adnan Aydiner, Ozgur Ozyilkan, Emel Sezer, Anne Armstrong, Sophie Barrett, Annabel Borley, Zoe Kemp, Caroline Michie, Mukesh Mukesh, Timothy Perren, Angela Swampillai, Tammy Young, Karen A Gelmon, Peter A Fasching, Fergus J Couch, Judith Balmaña, Suzette Delaloge, Intidhar Labidi-Galy, James Bennett, Susan McCutcheon, Graham Walker, Joyce O'Shaughnessy, Collaborating Investigators, Constanta Timcheva, Antoaneta Tomova, Andrea Eisen, Karen Gelmon, Julie Lemieux, Fernando Bazan, Hugues Bourgeois, Camille Chakiba, Mohamad Chehimi, Florence Dalenc, Thibault De La Motte Rouge, Jean-Sébastien Frenel, Anthony Gonçalves, Anne Claire Hardy-Bessard, Regine Lamy, Christelle Levy, Alain Lortholary, Audrey Mailliez, Jacques Medioni, Anne Patsouris, Dominique Spaeth, Luis Teixeira, Isabelle Tennevet, Cristian Villanueva, Benoit You, Johannes Ettl, Bernd Gerber, Oliver Hoffmann, Tjoung-Won Park-Simon, Mattea Reinisch, Joke Tio, Pauline Wimberger, Katalin Boer, Alberto Ballestrero, Giampaolo Bianchini, Laura Biganzoli, Roberto Bordonaro, Francesco Cognetti, Michelino De Laurentiis, Sabino De Placido, Valentina Guarneri, Filippo Montemurro, Giuseppe Naso, Armando Santoro, Claudio Zamagni, Seung-Jin Kim, Seigo Nakamura, Yee Soo Chae, Eun Kyung Cho, Kim Jee Hyun, Seock-Ah Im, Keun Seok Lee, Yeon Hee Park, Joo Hyuk Sohn, Tomasz Byrski, Tomasz Huzarski, Bozena Kukielka-Budny, Zbigniew Nowecki, Renata Szoszkiewicz, Rafal Tarnawski, Viktoria Dvornichenko, Fedor Moiseenko, Guzel Mukhametshina, Elena Poddubskaya, Ekaterina Popova, Anna Tarasova, Anna Vats, Bárbara Adamo, Raquel Andrés Conejero, Antonio Antón Torres, Judith Balmaña Gelpi, Nieves Díaz Fernández, Alejandro Falcón González, Juan Garcia, Isabel Lorenzo-Lorenzo, Fernando Moreno Antón, Marta Santisteban, Agostina Stradella, Chiun-Sheng Huang, Sercan Aksoy, Cagatay Arslan, Mehmet Artac, Adnan Aydiner, Ozgur Ozyilkan, Emel Sezer, Anne Armstrong, Sophie Barrett, Annabel Borley, Zoe Kemp, Caroline Michie, Mukesh Mukesh, Timothy Perren, Angela Swampillai, Tammy Young
Abstract
Background: In the phase III OlympiAD trial, olaparib significantly increased progression-free survival (PFS) compared with chemotherapy of physician's choice in patients with germline BRCA-mutated (gBRCAm), human epidermal growth factor 2 (HER2)-negative metastatic breast cancer (mBC). The phase IIIb LUCY trial assessed the clinical effectiveness of olaparib in similar patients, in a setting reflecting clinical practice.
Methods: This open-label, single-arm trial of olaparib (300 mg, twice daily) enrolled patients with BRCAm, HER2-negative mBC who had received taxane and/or anthracycline in the (neo)adjuvant/metastatic setting and not more than two lines of prior chemotherapy for mBC. Patients with hormone receptor-positive mBC had progressed on at least one line of endocrine therapy in an adjuvant/metastatic setting and were unsuitable for further endocrine treatment. This interim analysis was planned after 160 PFS events.
Results: Of 563 patients screened, 252 patients with gBRCAm were enrolled and received at least one dose of olaparib. The median investigator-assessed PFS was 8.11 months (95% confidence interval [CI], 6.93-8.67; 166/252 events [65.9% maturity]). The investigator-assessed clinical response rate was 48.6%, and median time to first subsequent treatment or death was 9.66 months (95% CI, 8.67-11.14). The most common treatment-emergent adverse events (TEAEs; >20% patients) were nausea, anaemia, asthenia, vomiting and fatigue. Eleven patients (4.4%) discontinued treatment because of a TEAE. Grade 3 or higher TEAEs occurred in 64 patients (25.4%), including anaemia (33 patients; 13.1%).
Conclusion: Olaparib was clinically effective in patients with gBRCAm, HER2-negative mBC with safety outcomes consistent with previous findings. ClinicalTrials.gov identifier: NCT03286842.
Keywords: BRCA1 gene; BRCA2 gene; Breast cancer; Effectiveness; Germline mutation; Metastatic; Olaparib; Progression-free survival; Treatment outcome.
Conflict of interest statement
Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. S. McCutcheon is an employee and stockholder of AstraZeneca LP. J. Bennett and G. Walker are contractors for AstraZeneca LP. The following authors have received compensation for serving as consultants or speakers, or they or the institutions they work for have received research support, from the companies or organizations indicated: K. A. Gelmon (AstraZeneca, Bristol-Myers Squibb, Genentech, Genomic Health, Janssen Oncology, Lilly, Merck, Mylan, NanoString Technologies, Novartis, Pfizer, and Roche); P. A. Fasching (Amgen, AstraZeneca, BionTech AG, Celgene, Cepheid, Daiichi Sankyo, Eisai, Hexal, Lilly, Macrogenics, Merck Sharp & Dohme, Myelo Therapeutics GmbH, Novartis, Pfizer, Puma Biotechnology, Roche, and Seattle Genetics); F. J. Couch (Ambry Genetics, AstraZeneca, GRAIL, and Qiagen); J. Balmaña (AstraZeneca, PharmaMar, and Pfizer); S. Delaloge (AstraZeneca, Lilly, Novartis, Pfizer, Puma Biotechnology, Roche/Genentech, and Sanofi); I. Labidi-Galy (AstraZeneca, Bristol-Myers Squibb, MSD Brazil, Novimmune, and PharmaMar); J. O'Shaughnessy (Abbvie, Agendia, Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene, Daiichi Sankyo, Eisai, Genentech, Genomic Health, GRAIL, HERON, Immunomedics, Ipsen, Jounce Therapeutics, Lilly, Merck Sharp & Dohme, Myriad Pharmaceuticals, Novartis, Ondonate, Pfizer, Puma Biotechnology, Roche, Samsung, Sanofi, Seattle Genetics, and Syndax). The authors have indicated that they have no other conflicts of interest regarding the content of this article.
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Source: PubMed