258MO - Niraparib plus abiraterone acetate plus prednisone (NIRA+AAP) as first-line treatment in patients with BRCA+ metastatic castration-resistant prostate cancer (mCRPC): Second interim analysis in the Asian subgroup of the MAGNITUDE study

Background

Patients with mCRPC and BRCA alterations have poor outcomes with current standard of care treatments. The phase 3 MAGNITUDE study found that patients with BRCA+ mCRPC benefit from first-line treatment with NIRA+AAP. Here we report results from the second interim analysis (IA2) for the subgroup of patients enrolled in Asia, focusing on BRCA1/2-positive (BRCA+) cohort.

Methods

The subgroup analysis reports updated data for the primary endpoint of radiographic progression-free survival (rPFS) by blinded independent central review (BICR). Additionally, the secondary endpoints of time to symptomatic progression (TSP), time to cytotoxic chemotherapy (TCC), and overall survival (OS) in the BRCA+ cohort, time to PSA progression (TPP) in the BRCA+ cohort and safety in the HRR+ cohort are also explored.

Results

The Asian subgroup included 36 BRCA+ pts. In the BRCA+ cohort, improvement in rPFS by BICR was observed with NIRA+AAP (N = 17) vs. PBO+AAP (N = 19), with 71% reduced risk of progression or death (HR, 0.29, 95% CI, 0.11, 0.77) (Table). NIRA+AAP extended median rPFS to 22 mos over 8 mos in PBO+AAP. NIRA+AAP also provided clinically relevant delays in TSP, TCC, and TPP. Although OS data were not mature, OS at 24 months was 66.9% in the NIRA+AAP group and 58.6% in PBO+AAP. In the all HRR+ population from Asia (N = 68), AEs were consistent with known side effects of NIRA and AAP. Grade 3/4 treatment-emergent adverse events (AEs) occurred in 71% in the NIRA+AAP group and 38% in PBO+AAP. Serious AEs were reported for 46% and 33% of pts, respectively, and 14% and 8% had AEs leading to discontinuation of the study drug. Safety results were consistent with IA1, with no new safety signals observed. Table: 258MO

Clinical outcomes in the Asian subgroup with BRCA+ mCRPC

NR, not reached. BICR, blinded independent central review. HR using a non-stratified proportional hazards model. HR <1 (bold) favors NIRA+AAP treatment; Nominal p-value is from a non-stratified log-rank test.

Conclusions

Longer follow-up of the Asian subgroup confirms initial observations of a benefit from NIRA+AAP in BRCA+ mCRPC pts, which is consistent with the overall MAGNITUDE study results.

Clinical trial identification

NCT03748641.

Editorial acknowledgement

Wirting assistance was provided by Joanne Wolter (independent) on behalf of Janssen Asia Pacific.

Legal entity responsible for the study

Janssen Asia Pacific, a division of Johnson & Johnson International (Singapore) Pte. Ltd.

Funding

Janssen Asia Pacific, a division of Johnson & Johnson International (Singapore) Pte. Ltd.

Disclosure

M. Saad: Financial Interests, Personal, Advisory Role: Johnson&Johnson, MSD, AstraZeneca, Novartis, Merck, Bristol Myers Squibb, Viatris, Ipsen; Financial Interests, Personal, Other, Honoraria: Astellas Pharma, Novartis, Johnson&Johnson, Ipsen, Cipla, AstraZeneca, Eisai, Pfizer, Amgen; Financial Interests, Personal, Research Grant: Johnson & Johnson, MSD. K.N. Chi: Financial Interests, Personal, Advisory Role: ESSA, Astellas Pharma, Janssen, Sanofi, Amgen, Bayer, AstraZeneca, Roche, POINT Biopharma, Daiichi Sankyo, Merck, Constellation Pharmaceuticals; Financial Interests, Personal, Expert Testimony: AstraZeneca, Novartis; Financial Interests, Personal, Other, Honoraria: Janssen, Astellas Pharma, Bayer, AstraZeneca, Roche, Merck; Financial Interests, Personal, Research Grant: Janssen, Astellas Pharma, Bayer, Sanofi, Bristol Myers Squibb, Merck, Roche, AstraZeneca, Novartis, Pfizer, ESSA. S.K. Sandhu: Financial Interests, Institutional, Advisory Role: AstraZeneca, Merck Sharp & Dohme, Bristol Myers Squibb/Roche; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb, Merck, Roche/Genentech; Financial Interests, Institutional, Other, Honoraria: Bristol Myers Squibb, Merck, Merck Serono, AstraZeneca; Financial Interests, Institutional, Research Grant: Amgen, AstraZeneca, Merck, Endocyte/Advanced Accelerator Applications, Genentech/Roche, Novartis. G. Attard: Financial Interests, Personal, Advisory Role: Janssen-Cilag, Veridex, Ventana Medical Systems, Astellas Pharma, Medivation, Novartis, Millennium, Abbott Laboratories, ESSA, Bayer, Pfizer, AstraZeneca, Ferring; Financial Interests, Personal, Speaker’s Bureau: Janssen, Astellas Pharma, Takeda, Sanofi, Ventana Medical Systems, Ipsen, AstraZeneca, Ferring; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Janssen, Astellas Pharma, Medivation, Ventana Medical Systems, Abbott Laboratories, Bayer, ESSA, Pfizer, Ferring; Other, Personal, Other, Immediate family member: Janssen, Astellas Pharma; Financial Interests, Personal, Royalties: Institute of Cancer Research; Financial Interests, Personal, Other, Honoraria: Janssen, Astellas Pharma; Financial Interests, Personal, Advisory Board, Honoraria, Immediate Family Member: Janssen; Financial Interests, Institutional, Research Grant: Janssen, Arno Therapeutics, Innocrin Pharma. P.S.J. Francis, S. Li, S. Dibaj, J. Zhang, W. Kim, A. Lopez-Gitlitz, D. Wu, A. Singh, R. De Vries, L. Zhang: Financial Interests, Personal, Full or part-time Employment: Janssen (Johnson & Johnson); Financial Interests, Personal, Stocks/Shares: Janssen (Johnson & Johnson). All other authors have declared no conflicts of interest.