Abstract 260P
Background
Niraparib is a potent, highly selective, PARP 1/2 inhibitor with clinical activity for patients (pts) with ovarian and breast cancer that harbor germline BRCA mutations (gBRCAm). LUZERN evaluated the efficacy and safety of niraparib plus AI for AI-resistant HR+/HER2- advanced breast cancer (ABC) pts with gBRCAm or homologous recombinant deficient (HRD)/non-gBRCAm.
Methods
LUZERN (NCT04240106) was an open-label, single-arm, two-cohort, Simon Two-Stage, phase II clinical trial. Pts with HR+/HER2- ABC and gBRCAm (cohort A) or HRD/non-gBRCAm (cohort B) who had received ≤1 line chemotherapy (ChT) and 1-2 prior lines of endocrine therapy (± targeted therapy) for ABC, with secondary resistance to the last AI-based regimen, were eligible. Pts received niraparib (200/300 mg daily orally) and AI (same as prior regimen) on each 28-day cycle. Luteinizing hormone-releasing hormone analogs were mandatory for pre- and peri-menopausal pts. The primary endpoint was clinical benefit rate (CBR) as per RECIST v.1.1. Secondary endpoints included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), duration of response (DoR), and safety.
Results
Between June 2020 and November 2022, 14 pts enrolled in cohort A (6 pts stage 1; 8 pts stage 2). No pts were enrolled in cohort B. 35% had previously received one line of non-platinum-based ChT and 92.9% received a CDK4/6 inhibitor-based regimen for advanced disease. Median follow-up was 16.7 months (mo) (IQR, 13.2-18.2 months). CBR was 50% (95% CI, 26.4–67.5%; p<0.001) (2 complete responses, 2 partial responses, and 3 stable disease ≥24 weeks), meeting the primary endpoint. ORR was 28.6% (95% CI, 8.4%-58.1%) with a median DoR of 5.6 (95% CI, 2.2-8.8) mo, median PFS was 6.9 (95% CI, 3.9-10.5) mo, and median OS was 18.1 (95% CI, 13.2-NE) mo. The most common treatment-emergent adverse events (TEAEs) were fatigue (71.4%), nausea (57.1%), and neutropenia (50%). There were no grade 4/5 TEAEs.
Conclusions
Niraparib plus AI has encouraging antitumor activity and a manageable safety profile for pts with pretreated AI-resistant HR+/HER2- ABC with gBRCAm, warranting further research of the combination.
Clinical trial identification
NCT04240106.
Legal entity responsible for the study
Medica Scientia Innovation Research (MEDSIR).
Funding
GSK.
Disclosure
J. Balmaña: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Other, Educational programs: AstraZeneca -MSD; Financial Interests, Institutional, Invited Speaker: AstraZeneca, MedSir. J. García Saenz: Financial Interests, Personal, Advisory Role: Seagen, AstraZeneca, Daiichi Sankyo, Novartis, Gilead, Menarini; Financial Interests, Personal, Invited Speaker: Celgene, Eli Lilly, Eisai, MSD, Exact Sciences, Tecnofarma, Nolver (adium), Asofarma, Roche; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Personal, Other, travel: Gilead, AstraZeneca, Daiichi Sankyo. B. Jiménez-Rodríguez: Financial Interests, Personal, Advisory Role: Novartis, Lilly, Roche, Daiichi Sankyo, Esteve. J.M. Pérez García: Financial Interests, Personal, Full or part-time Employment: MEDSIR; Financial Interests, Personal, Advisory Role: Lilly, Roche, Eisai, Daiichi Sankyo, AstraZeneca, Seagen, Gilead; Financial Interests, Personal, Other, travel expenses: Roche. M. Campolier: Financial Interests, Personal, Full or part-time Employment: MEDSIR. E. Shimizu: Financial Interests, Personal, Full or part-time Employment: MEDSIR. D. Alcalá-López: Financial Interests, Personal, Full or part-time Employment: MEDSIR. M. Sampayo Cordero: Financial Interests, Personal, Full or part-time Employment: MEDSIR. J. Cortes Castan: Financial Interests, Personal, Advisory Role: Roche, AstraZeneca, Seagen, Daiichi Sankyo, Lilly, Merck Sharp and Dohme, Leuko, Bioasis, Clovis Oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks, Reveal Genomics, Scorpion Therapeutics, EXpres2ion Biotechnologies, Jazz Pharmaceuticals, AbbVie, BridgeBio, Biontech; Financial Interests, Personal, Other, honoraria: Roche, Novartis, Eisai, Pfizer, Lilly, Merck Sharpe and Dohme, Daiichi Sankyo, AstraZeneca, Gilead, Stemline Therapeautics; Financial Interests, Institutional, Funding: Roche, Araid Pharmaceuticals, AstraZeneca, Baxalta GMBH/Sevier Affaires, Bayer Healthcare, Eisai, F Hoffman-La Roche, Guardant Health, Merck Sharp & Dohme, Pfizer, Piqur Therapeutics, IQVIA, Queen Mary of London; Financial Interests, Personal, Stocks/Shares: MAJ3 Capital, Leuko; Financial Interests, Personal, Other, travel: Roche, Novartis, Eisai, Pfizer, Daiichi Sankyo, AstraZeneca, Gilead, MSD, Stemline Therapeutics. A. Llombart Cussac: Financial Interests, Personal, Research Grant: Roche, Agendia, Lilly, Pfizer, Novartis, Merck Sharp and Dohme, Gilead, Daiichi Sankyo; Financial Interests, Personal, Speaker’s Bureau: Lilly, Roche, Pfizer, Novartis; Financial Interests, Personal, Other, travel: Roche, Pfizer, AstraZeneca, Stemline Therapeutics, Merck Sharp & Dohme; Financial Interests, Personal, Stocks/Shares: MAJ3 Capital, Initia Research. All other authors have declared no conflicts of interest.