Abstract 582P
Background
The phase II open-label GALAHAD study evaluated niraparib in mCRPC patients (pts) with DRD who had progressed on prior taxane-based chemotherapy and androgen signaling inhibitor therapy. We report on the HRQoL outcomes at final analysis.
Methods
DRD altered pts were categorized as BRCA (BRCA1 or BRCA2) or non-BRCA (ATM, FANCA, PALB2, CHEK2, BRIP1, HDAC2). HRQoL assessments (at Day 1 of specified cycles, C) included the Functional Assessment of Cancer Therapy–Prostate Total Score (FACT-P TS) and Brief Pain Inventory–Short Form (BPI-SF). Changes from baseline HRQoL were compared for BRCA vs non-BRCA pts using a mixed model for repeated measures. Pts were classified as improved/stable or worsened based on established meaningful change thresholds. Generalized estimating equations were used to calculate odds ratios of HRQoL improvement using non-BRCA as the reference category.
Results
Of 223 pts (ITT population), 221 pts completed the HRQoL evaluations at baseline (BRCA, n=140; non-BRCA, n=81). Subsets of both cohorts experienced improved/stable HRQoL, pain intensity, and pain interference, which tended to be more pronounced in BRCA pts (Table). Numerically similar or greater proportions of BRCA pts had improved/stable FACT-P TS/BPI-SF scores vs non-BRCA pts, with differences apparent and widening at earlier cycles (by C5; Table). BRCA pts had 2.4 times greater odds of experiencing clinically meaningful improvements in overall HRQoL (FACT-P TS) than non-BRCA pts by C3, with 4.4 times greater odds of improving by C5. BRCA pts were also significantly more likely than non-BRCA pts to experience meaningful reductions in pain intensity and interference (Table).
Conclusions
Niraparib improved/maintained overall HRQoL, pain intensity, and pain interference in advanced mCRPC. Among these pts, those with BRCA alterations had greater benefits. Table: 582P
| Improved or stable, n (%) | Worsened, n (%) | BRCA vs. non- BRCA (Odds of improvement) | ||||
| BRCA | Non-BRCA | BRCA | Non-BRCA | OR | 95% CI | |
| FACT-P TS | ||||||
| C3 | 94 (82) | 41 (71) | 21 (18) | 17 (29) | 2.4 | (1.2, 5.0) |
| C5 | 75 (85) | 21 (64) | 13 (15) | 12 (36) | 4.4 | (1.5, 13.2) |
| C7 | 58 (79) | 14 (70) | 15 (21) | 6 (30) | 2.0 | (0.5, 7.8) |
| C10 | 36 (82) | 6 (67) | 8 (18) | 3 (33) | 1.7 | (0.2, 13.6) |
| BPI-SF Pain Intensity | ||||||
| C3 | 97 (87) | 48 (84) | 15 (13) | 9 (16) | 1.4 | (0.6, 3.3) |
| C5 | 71 (84) | 28 (85) | 14 (16) | 5 (15) | 1.6 | (0.6, 4.3) |
| C7 | 60 (85) | 14 (74) | 11 (15) | 5 (26) | 0.9 | (0.3, 3.1) |
| C10 | 35 (83) | 8 (100) | 7 (17) | 0 (0) | 0.2 | (0.0, 2.2) |
| BPI-SF Pain Interference | ||||||
| C3 | 86 (78) | 45 (80) | 24 (22) | 11 (20) | 1.6 | (0.7, 3.4) |
| C5 | 72 (88) | 23 (72) | 10 (12) | 9 (28) | 4.4 | (1.3, 15.2) |
| C7 | 63 (91) | 13 (68) | 6 (9) | 6 (32) | 1.2 | (0.3, 4.9) |
| C10 | 35 (81) | 6 (75) | 8 (19) | 2 (25) | 1.5 | (0.2, 11.2) |
Clinical trial identification
NCT02854436.
Editorial acknowledgement
Medical writing and editorial assistance was provided by Michelle Kwon, PhD of Cello Health Communications/MedErgy (Yardley, PA, USA) and was funded by Janssen Global Services, LLC.
Legal entity responsible for the study
Janssen Research & Development.
Funding
Janssen Research & Development.
Disclosure
M.R. Smith: Financial Interests, Personal and Institutional, Research Grant: Bayer; Financial Interests, Personal and Institutional, Advisory Role, Honoraria: Bayer; Financial Interests, Personal and Institutional, Research Grant: Amgen; Financial Interests, Personal and Institutional, Advisory Role, Honoraria: Amgen; Financial Interests, Personal and Institutional, Advisory Role, Honoraria: Astellas; Financial Interests, Personal and Institutional, Advisory Role, Honoraria: Janssen; Financial Interests, Personal and Institutional, Research Grant: Janssen; Financial Interests, Personal and Institutional, Research Grant: Lilly; Financial Interests, Personal and Institutional, Advisory Role, Honoraria: Lilly; Financial Interests, Personal and Institutional, Advisory Role, Honoraria: Novartis; Financial Interests, Personal and Institutional, Advisory Role, Honoraria: Pfizer. D.J. George: Financial Interests, Personal, Licensing Fees, Sr. Editor: American Association for Cancer Research; Financial Interests, Personal and Institutional, Research Grant, Consultant, Research, Ad Brd: Astellas; Financial Interests, Personal, Advisory Board, Consultant, Research, Ad Brd: Astellas; Financial Interests, Personal, Advisory Board, Consultant, Research, Ad Brd, SC: AstraZeneca; Financial Interests, Institutional, Research Grant, Consultant, Research, Ad Brd, SC: AstraZeneca; Financial Interests, Personal, Other, Independent Contractor: Axess Oncology; Non-Financial Interests, Personal and Institutional, Other, Consultant, Speaker, Honorarium, Travel Accomodations: Bayer H/C Pharmaceuticals; Financial Interests, Personal and Institutional, Research Grant, Consultant, Research, SC: BMS; Financial Interests, Institutional, Research Grant: Calithera; Financial Interests, Personal, Advisory Board, Scientific Advisory Board: Capio Biosciences; Financial Interests, Personal, Other, Consultant: Constellation Pharma; Financial Interests, Personal, Other, Honorarium: EMD Serono; Non-Financial Interests, Personal and Institutional, Research Grant, Consultant, Research, Speaker, Honorarium, Travel Accomodations: Exelixis, Inc; Financial Interests, Personal, Other, Consultant: Flatiron; Financial Interests, Personal, Other, Honorarium: Ipsen; Financial Interests, Personal and Institutional, Research Grant, Consultant, Research, IDMC: Janssen Pharma; Financial Interests, Personal, Other, Consultant: Merck Sharp & Dohme; Financial Interests, Personal, Other, Consultant, Honorarium: Michael J Hennessey Assoc; Financial Interests, Personal, Invited Speaker, Co-Editor-in-Chief: Millennium Medical Publishing; Financial Interests, Personal, Advisory Board: Modra Pharma; Financial Interests, Personal, Other, Consultant: Myovant Sciences, Inc; Financial Interests, Personal, Other, Steering Committee: NCI Genitourinary; Financial Interests, Personal, Other, Steering Committee: Nektar Therapeutics; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Personal, Other, Consultant: Physician Education Resource; Financial Interests, Personal and Institutional, Research Grant, Consultant, Research, SC, Honorarium: Pfizer; Financial Interests, Personal, Other, Consultant: Propella TX; Financial Interests, Personal, Other, Consultant: RevHealth, LLC; Non-Financial Interests, Personal and Institutional, Research Grant, Consultant, Research, Speaker, Honorarium, Travel Accomodations: Sanofi; Financial Interests, Personal, Other, Honorarium: UroGPO; Non-Financial Interests, Personal, Other, Honorarium, Travel Accomodations: UroToday. K.N. Chi: Financial Interests, Institutional, Research Grant, Institution for clinical trial conduct: Janssen; Financial Interests, Institutional, Research Grant, Personal fees for consulting. Research contracts with institution for clinical trial conduct: AstraZeneca; Financial Interests, Personal, Licensing Fees, Personal fees for consulting. Research contracts with institution for clinical trial conduct: AstraZeneca; Financial Interests, Institutional, Research Grant, Personal fees for consulting. Research contracts with institution for clinical trial conduct: Bayer; Financial Interests, Personal, Licensing Fees, Personal fees for consulting. Research contracts with institution for clinical trial conduct: Bayer; Financial Interests, Institutional, Research Grant, Personal fees for consulting. Research contracts with institution for clinical trial conduct: Astellas; Financial Interests, Personal, Licensing Fees, Personal fees for consulting. Research contracts with institution for clinical trial conduct: Astellas; Financial Interests, Personal, Other, Personal fees for consulting: Daiichi Sankyo; Financial Interests, Institutional, Research Grant, Personal fees for consulting. Research contracts with institution for clinical trial conduct: Novartis; Financial Interests, Personal, Licensing Fees, Personal fees for consulting. Research contracts with institution for clinical trial conduct: Novartis; Financial Interests, Institutional, Research Grant, Personal fees for consulting. Research contracts with institution for clinical trial conduct: Pfizer; Financial Interests, Personal, Licensing Fees, Personal fees for consulting. Research contracts with institution for clinical trial conduct: Pfizer; Financial Interests, Institutional, Research Grant, Personal fees for consulting. Research contracts with institution for clinical trial conduct: Point Biopharma; Financial Interests, Personal, Licensing Fees, Personal fees for consulting. Research contracts with institution for clinical trial conduct: Point Biopharma; Financial Interests, Institutional, Research Grant, Personal fees for consulting. Research contracts with institution for clinical trial conduct: Roche; Financial Interests, Personal, Licensing Fees, Personal fees for consulting. Research contracts with institution for clinical trial conduct: Roche; Financial Interests, Institutional, Research Grant, Personal fees for consulting. Research contracts with institution for clinical trial conduct: Sanofi; Financial Interests, Personal, Licensing Fees, Personal fees for consulting. Research contracts with institution for clinical trial conduct: Sanofi; Financial Interests, Personal, Licensing Fees, Personal fees for consulting: Merck; Financial Interests, Personal, Licensing Fees, Personal fees for consulting: Bristol-Myers Squibb. F. Saad: Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Personal, Licensing Fees: Janssen; Non-Financial Interests, Personal, Other: Janssen; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Licensing Fees: AstraZeneca; Non-Financial Interests, Personal, Other: AstraZeneca; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Personal, Licensing Fees: Astellas; Non-Financial Interests, Personal, Other: Astellas; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Personal, Licensing Fees: Pfizer; Non-Financial Interests, Personal, Other: Pfizer; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Personal, Licensing Fees: Bayer; Financial Interests, Personal, Other: Bayer; Financial Interests, Institutional, Research Grant: Myovant; Financial Interests, Personal, Licensing Fees: Myovant; Non-Financial Interests, Personal, Other: Myovant; Financial Interests, Institutional, Funding: Sanofi; Financial Interests, Personal, Licensing Fees: Sanofi; Non-Financial Interests, Personal, Other: Sanofi; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Personal, Licensing Fees: Novartis; Financial Interests, Personal, Other: Novartis. A. Thiery-Vuillemin: Financial Interests, Institutional, Research Grant, Honoraria; Consulting or Advisory Role; Research Funding; Travel, Accommodations, Expenses: Pfizer; Financial Interests, Personal and Institutional, Advisory Role, Honoraria; Consulting or Advisory Role; Research Funding; Travel, Accommodations, Expenses: Pfizer; Non-Financial Interests, Personal, Other: Pfizer; Financial Interests, Personal and Institutional, Advisory Role, Honoraria; Consulting or Advisory Role; Travel, Accommodations, Expenses: AstraZeneca; Financial Interests, Institutional, Research Grant, Honoraria; Consulting or Advisory Role; Travel, Accommodations, Expenses: AstraZeneca; Non-Financial Interests, Personal, Other: AstraZeneca; Financial Interests, Personal and Institutional, Advisory Role, Honoraria; Consulting or Advisory Role: Sanofi; Non-Financial Interests, Personal, Other: Janssen; Financial Interests, Personal, Advisory Role, Honoraria; Consulting or Advisory Role; Travel, Accommodations, Expenses: Janssen; Financial Interests, Personal, Advisory Role, Honoraria; Consulting or Advisory Role: Novartis; Financial Interests, Personal, Advisory Role, Honoraria; Consulting or Advisory Role: Ipsen; Non-Financial Interests, Personal, Other: Ipsen; Financial Interests, Personal, Advisory Role, Honoraria; Consulting or Advisory Role; Travel, Accommodations, Expenses: Roche/Genentech; Non-Financial Interests, Personal, Other: Roche/Genentech; Financial Interests, Personal, Advisory Role, Honoraria; Consulting or Advisory Role: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role, Honoraria; Consulting or Advisory Role; Travel, Accommodations, Expenses: MSD; Non-Financial Interests, Personal, Other: MSD; Financial Interests, Personal, Advisory Role, Honoraria; Consulting or Advisory Role; Travel, Accommodations, Expenses: Astellas Pharma; Non-Financial Interests, Personal, Other: Astellas Pharma. D. Olmos: Financial Interests, Institutional, Research Grant, Research grant (institution), Advisory board, Clinical Trial Steering committee (Nonc-ompensated), Travel support, speaker fees: AstraZeneca; Financial Interests, Personal, Advisory Board, Research grant (institution), Advisory board, Clinical Trial Steering committee (Nonc-ompensated), Travel support, speaker fees: AstraZeneca; Financial Interests, Institutional, Research Grant, Research grant (institution), Advisory board, Clinical Trial Steering committee (Nonc-ompensated), Travel support, speaker fees: Bayer; Financial Interests, Personal, Advisory Board, Research grant (institution), Advisory board, Clinical Trial Steering committee (Nonc-ompensated), Travel support, speaker fees: Bayer; Non-Financial Interests, Personal, Other: Bayer; Financial Interests, Personal, Advisory Board: Clovis; Financial Interests, Personal, Advisory Board: Daiichi-Sankyo; Non-Financial Interests, Personal, Other, Clinical Trial Steering committee (Nonc-ompensated), Travel support: F. Hoffman La Roche; Other, Travel support: Ipsen; Financial Interests, Institutional, Research Grant, Research grant (institution), Advisory board, Clinical Trial Steering committee (Nonc-ompensated), Travel support, speaker fees: Janssen; Financial Interests, Personal, Advisory Board, Advisory board, speaker fees: MSD. R. Gafanov: Financial Interests, Research Grant: Janssen. E. Castro: Financial Interests, Personal and Institutional, Licensing Fees, My institution received fees from Janssen for the patients enrolled in the GALAHAD trial: Janssen; Financial Interests, Personal and Institutional, Licensing Fees: Astellas. H. Moon: Financial Interests, Personal and Institutional, Advisory Board, Consulting fees: Bayer Pharmaceutical; Financial Interests, Personal and Institutional, Invited Speaker: Pfizer; Non-Financial Interests, Personal, Other: Dendreon. A.M. Joshua: Financial Interests, Institutional, Other: Janssen. G.E. Mason: Non-Financial Interests, Personal, Other, Medical writing and editorial assistance: MedErgy; Financial Interests, Institutional, Full or part-time Employment: Janssen (Johnson & Johnson). B.M. Espina: Financial Interests, Institutional, Stocks/Shares: Janssen Research and Development. K.B. Bevans: Financial Interests, Institutional, Full or part-time Employment: Janssen; Financial Interests, Institutional, Stocks/Shares: Johnson and Johnson. A. Lopez-Gitlitz: Financial Interests, Personal and Institutional, Full or part-time Employment: Janssen; Financial Interests, Institutional, Stocks/Shares: Janssen. P. Francis: Financial Interests, Personal, Other, Medical writing and editorial assistance: MedErgy; Financial Interests, Institutional, Full or part-time Employment: Janssen (Johnson & Johnson). K. Fizazi: Financial Interests, Institutional, Advisory Board: AAA; Financial Interests, Institutional, Advisory Board: Astellas; Financial Interests, Institutional, Invited Speaker: Astellas; Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Advisory Board: Bayer; Financial Interests, Institutional, Invited Speaker: Bayer; Financial Interests, Personal, Advisory Board: Curevac; Financial Interests, Institutional, Advisory Board: Janssen; Financial Interests, Institutional, Invited Speaker: Janssen; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: Orion; Financial Interests, Institutional, Invited Speaker: Sanofi; Financial Interests, Institutional, Research Grant, Trial chair: AstraZeneca; Financial Interests, Institutional, Research Grant, Trial chair: Bayer; Financial Interests, Institutional, Research Grant, Trial chair: BMS; Financial Interests, Institutional, Research Grant, Trial chair: Janssen; Financial Interests, Institutional, Research Grant, Trial chair: MSD; Financial Interests, Institutional, Research Grant, Trial chair: Orion; Financial Interests, Institutional, Research Grant, Trial chair: Pfizer. All other authors have declared no conflicts of interest.