Clinical effectiveness of olaparib monotherapy in germline BRCA-mutated, HER2-negative metastatic breast cancer in a real-world setting: phase IIIb LUCY interim analysis

Gelmon, Karen A.; Fasching, Peter A.; Couch, Fergus J.; Balmañà, Judith; Delaloge, Suzette; Labidi-Galy, Intidhar; Bennett, James; McCutcheon, Susan; Walker, G.P.; O’Shaughnessy, Joyce; Timcheva, Constanta; Tomova, Antoaneta; Eisen, Andrea; Gelmon, Karen A.; Lemieux, Julie; Bazán, Fernando; Bourgeois, H.; Chakiba, Camille; Chehimi, Mohamad; Dalenc, Florence; Rouge, Thibault De La Motte; Frenel, Jean‐Sébastien; Gonçalvès, Anthony; Hardy-Bessard, Anne Claire; Lamy, R.; Lévy, Christelle; Lortholary, Alain; Mailliez, Audrey; Médioni, Jacques; Patsouris, Anne; Spaëth, Dominique; Teixeira, Luís; Tennevet, Isabelle; Villanueva, Cristian; You, Benoît; Ettl, Johannes; Gerber, Bernd; Hoffmann, Oliver; Park‐Simon, Tjoung‐Won; Reinisch, Mattea; Tio, Joke; Wimberger, Pauline; Boér, Katalin; Ballestrero, Alberto; Bianchini, Giampaolo; Biganzoli, Laura; Bordonaro, Roberto; Cognetti, F.; Laurentiis, Michelino De; Placido, Sabino De; Guarneri, Valentina; Montemurro, Filippo; Naso, Giuseppe; Santoro, Armando; Zamagni, Claudio; Kim, Seung-Jin; Nakamura, Seigo; Chae, Yee Soo; Cho, Eun Kyung; Hyun, Kim Jee; Im, Seock‐Ah; Lee, Keun Seok; Park, Yeon Hee; Sohn, Joohyuk; Byrski, Tomasz; Huzarski, Tomasz; Kukiełka-Budny, Bożena; Nowecki, Zbigniew; Szoszkiewicz, Renata; Tarnawski, R.; Дворниченко, В. В.; Моисеенко, Ф. В.; Mukhametshina, Guzel; Poddubskaya, Elena; Попова, Е. В.; Tarasova, Anna; Vats, Anna; Adamo, Bárbara; Conejero, Raquel Andrés; Torres, A. Antón; Gelpí, Judith Balmaña; Fernández, Nieves Díaz; González, Alejandro Falcón; García, J. Hernández; Lorenzo-Lorenzo, Isabel; Antón, Fernando Moreno; Santisteban, Marta; Stradella, Agostina; Huang, Chiun‐Sheng; Aksoy, Sercan; Arslan, Çağatay; Artaç, Mehmet; Aydıner, Adnan; Özyılkan, Özgür; Sezer, Emel; Armstrong, Anne; Barrett, Sophie; Borley, Annabel; Kemp, Zoe; Michie, Caroline O.; Mukesh, Mukesh; Perren, Timothy; Swampillai, Angela; Young, Tammy

doi:10.1016/j.ejca.2021.03.029

Cited by 21 publications

(20 citation statements)

References 20 publications

(20 reference statements)

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“…Patients with hormone-receptor-positive disease should have received and progressed on a prior endocrine therapy [ 14 ]. The results of a recent phase IIIb trial were consistent with previous findings and reported an ORR of 50% in a similar patient population [ 86 ].…”

Section: Olaparibsupporting

confidence: 90%

PARP Inhibitors for Breast Cancer: Germline BRCA1/2 and Beyond

Menezes

Raheem

Mina

et al. 2022

Cancers

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Poly-adenosine diphosphate ribose polymerase (PARP) inhibitors (PARPi) are approved for BRCA1/2 carriers with HER2-negative breast cancer in the adjuvant setting with a high risk of recurrence as well as the metastatic setting. However, the indications for PARPi are broader for patients with other cancer types (e.g., prostate and ovarian cancer), involving additional biomarkers (e.g., ATM, PALB2, and CHEK) and genomic instability scores. Herein, we summarize the data on PARPi and breast cancer and discuss their use beyond BRCA carriers.

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Section: Olaparibsupporting

confidence: 90%

PARP Inhibitors for Breast Cancer: Germline BRCA1/2 and Beyond

Menezes

Raheem

Mina

et al. 2022

Cancers

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“…]18 months, as compared to previous studies. The median progression-free survival was 7.0 to 8.6 months in the phase III trials [19,[22][23][24][25][26][27]. In all three patients of our study, olaparib was administered relatively early because these patients had received prior neoadjuvant or adjuvant chemotherapy.…”

Section: Discussionmentioning

confidence: 89%

“…Thus, there are increasing opportunities for cancer treatment with PARP inhibitors based on pathogenic variants ofBRCA 1/2 . However, based on several clinical trials including OlympiAD trial, Olaparib is allowed to use after prior anthracycline-and taxane-based therapies [16][17][18][19]. This sometimes prevents early introduction of PARP inhibitors due to lack of previous these chemotherapies.…”

Section: Introductionmentioning

confidence: 99%

Does early olaparib administration improve prognosis in patients with HER2-negative metastatic breast cancer and BRCA1 and/or BRCA2 pathogenic variants?: Finding from four cases

Takuwa

Sasaki

Yamada

et al. 2022

Preprint

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“…In these two trials, both triple-negative (TN) and oestrogen receptor positive (ERþ)/HER2-mBC patients benefited from PARP inhibitors. Olaparib effects were further supported in the phase IIIb LUCY study [10]. Veliparib, another PARP inhibitor, also showed its superiority in combination with platinum-based chemotherapy compared with chemotherapy alone in terms of PFS (14.5 versus 12.6 months; p Z 0.002) in patients with HER2-untreated mBC with gBRCA1/2 mutation [11].…”

Section: Introductionmentioning

confidence: 86%

Rucaparib in patients presenting a metastatic breast cancer with homologous recombination deficiency, without germline BRCA1/2 mutation

Patsouris

Diop²,

Trédan

et al. 2021

European Journal of Cancer

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Background: Breast cancer may present genomic alterations leading to homologous recombination deficiency (HRD). PARP inhibitors have proven their efficacy in patients with HER2-negative (HER2-) metastatic breast cancer (mBC) harbouring germline (g) BRCA1/2 mutations in 3 phases III trials. The single-arm phase II RUBY trial included 42 patients, 40 of whom received at least one dose of rucaparib. RUBY study assessed the efficacy of rucaparib in HER2-mBC with either high genomic loss of heterozygosity (LOH) score or non-germline BRCA1/2 mutation. Patients and methods: The primary objective was the clinical benefit rate (CBR), and the study was powered to see 20% CBR using a 2-stage Simon design. Results: The primary-end point was not reached with a CBR of 13.5%. Two LOH-high patients, without somatic BRCA1/2 mutation, presented a complete and durable response (12 and 28.5 months). Whole-genome analysis was performed on 24 samples, including 5 patients who presented a clinical benefit from rucaparib. HRDetect tended to be associated with response to rucaparib, without reaching statistical significance (median HRDetect responders versus non-responders: 0.465 versus 0.040; p Z 0.2135). Finally, 220 of 711 patients with mBC screened for LOH upstream from RUBY presented a high LOH score associated with a higher likelihood of death (hazard ratio Z 1.39; 95% CI: 1.11e1.75; p Z 0.005). Conclusion: Our data suggest that a small subset of patients with high LOH scores without germline BRCA1/2 mutation could derive benefit from PARP inhibitors. However, the RUBY study underlines the need to develop additional biomarkers to identify selectively potential responders.

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Clinical effectiveness of olaparib monotherapy in germline BRCA-mutated, HER2-negative metastatic breast cancer in a real-world setting: phase IIIb LUCY interim analysis

Cited by 21 publications

References 20 publications

PARP Inhibitors for Breast Cancer: Germline BRCA1/2 and Beyond

PARP Inhibitors for Breast Cancer: Germline BRCA1/2 and Beyond

Does early olaparib administration improve prognosis in patients with HER2-negative metastatic breast cancer and BRCA1 and/or BRCA2 pathogenic variants?: Finding from four cases

Rucaparib in patients presenting a metastatic breast cancer with homologous recombination deficiency, without germline BRCA1/2 mutation

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