Abstract 585P
Background
In IPATential150 (NCT03072238), ipat + abi as first-line mCRPC treatment (tx) significantly reduced the risk for disease worsening or death vs placebo (pbo) + abi in patients (pts) with tumours with PTEN loss status by IHC (HR, 0.77; 95% CI: 0.61, 0.98; P = 0.034) but not in the ITT population (de Bono ESMO 2020). Ipat + abi had a safety profile consistent with each agent’s known toxicities. Here, we further characterise the nature and manageability of AEs associated with ipat and abi from IPATential150, the first Ph III trial of AKT plus androgen biosynthesis inhibition for mCRPC.
Methods
Pts with mCRPC were randomised 1:1 to receive ipat (400 mg/d) + abi (1000 mg/d) + prednisone (5 mg bid) or pbo + abi + prednisone. Safety assessments included incidence, severity and relatedness to tx of AEs.
Results
The safety profile of ipat + abi was similar in the safety population (n=551 in ipat + abi arm) and in pts with PTEN loss by IHC (n=263 in ipat + abi arm): Gr 3-5 AEs, 70% vs 68%; serious AEs, 40% vs 39%, respectively. Similarly, the ipat + abi safety profile was comparable in Asian (n=109 in ipat + abi arm) and non-Asian pts (n=407 in ipat + abi arm): Gr 3-5 AEs, 65% vs 71%; serious AEs, 36% vs 40%, respectively. The most frequent AEs were asthenia and diarrhoea with pbo + abi (≥20% in n=546) and diarrhoea, hyperglycaemia and rash with ipat + abi (≥40% in n=551). AEs leading to discontinuation of pbo or ipat occurred in 5% of pbo + abi pts (0 diarrhoea; <1% rash in n=546) and 21% of ipat + abi pts (4% diarrhoea; 3% rash in n=551). Time to onset and reversibility of select AEs are shown (Table).
Conclusions
Overall, AEs were manageable and reversible in IPATential150 and were consistent with the ph II A. MARTIN trial. While more AEs leading to drug discontinuation were observed with ipat + abi vs pbo + abi, it is anticipated this will be lessened in the future with prophylactic measures, as in breast cancer studies with ipat. Table: 585P
| Selected AEs (all grade) | Pbo + Abi n=546 | Ipat + Abi n=551 |
| Diarrhoea, n (%) | 123 (23) | 440 (80) |
| Time to onset,a median (range), days | 69 (1-902) | 7.5 (1-560) |
| Duration,a median (rangeb), days | 4 (1-491) | 27 (1-948) |
| Pts with AE resolution, n (%)c | 117 (95) | 362 (82) |
| Hyperglycaemia, n (%) | 100 (18) | 264 (48)d |
| Time to onset,a median (range), days | 104 (1-657) | 29 (1-710) |
| Duration,a median (rangeb), days | 57 (1-853) | 43 (1-923) |
| Pts with AE resolution, n (%)c | 68 (68) | 198 (75) |
| Rash, n (%) | 62 (11) | 228 (41) |
| Time to onset,a median (range), days | 70 (2-638) | 20.5 (1-916) |
| Duration,a median (rangeb), days | 26.5 (1-848) | 24 (1-743) |
| Pts with AE resolution, n (%)c | 51 (82) | 207 (91) |
a Of first AE.b Includes censored time.c Among pts with AE.d 1 Grade 5 AE.
Clinical trial identification
NCT03072238.
Editorial acknowledgement
Medical writing assistance for this abstract was provided by Scott Battle, PhD, of Health Interactions, Inc., and funded by F. Hoffmann-La Roche Ltd.
Legal entity responsible for the study
F. Hoffmann-La Roche Ltd.
Funding
F. Hoffmann-La Roche Ltd.
Disclosure
C.N. Sternberg: Financial Interests, Personal, Advisory Board, AD board and speaker at ESMO: Pfizer; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Sanofi-Genzyme; Financial Interests, Personal, Advisory Board: Roche-Genentech; Financial Interests, Personal, Advisory Board: Foundation Medicine; Financial Interests, Personal, Advisory Board: Immunomedics; Financial Interests, Personal, Advisory Board: Janssen. S. Bracarda: Financial Interests, Advisory Role: Bayer Schering Pharma; Financial Interests, Advisory Role: Bristol-Myers Squibb; Financial Interests, Advisory Role: Ipsen; Financial Interests, Advisory Role: MSD Oncology; Financial Interests, Advisory Role: Pfizer; Financial Interests, Advisory Role: Roche/Genentech; Financial Interests, Other, Travel, Accommodations, Expenses: Astellas Pharma; Financial Interests, Other, Travel, Accommodations, Expenses: AstraZeneca; Financial Interests, Other, Travel, Accommodations, Expenses: Bristol-Myers Squibb; Financial Interests, Other, Travel, Accommodations, Expenses: Exelixis/Ipsen; Financial Interests, Other, Travel, Accommodations, Expenses: Ipsen; Financial Interests, Other, Travel, Accommodations, Expenses: Janssen Oncology; Financial Interests, Other, Travel, Accommodations, Expenses: Pfizer; Financial Interests, Other, Travel, Accommodations, Expenses: Roche. J.S. de Bono: Financial Interests, Full or part-time Employment: Institute of Cancer Research; Financial Interests, Other, Honoraria; Travel, Accommodations, Expenses: Amgen; Financial Interests, Other, Honoraria; Travel, Accommodations, Expenses: Astellas Pharma; Financial Interests, Other, Honoraria: Astex Pharmaceuticals; Financial Interests, Other, Honoraria; Travel, Accommodations, Expenses: AstraZeneca; Financial Interests, Other, Honoraria; Travel, Accommodations, Expenses: Bayer; Financial Interests, Other, Honoraria; Travel, Accommodations, Expenses: BioExcel; Financial Interests, Other, Honoraria; Travel, Accommodations, Expenses: Boehringer Ingelheim; Financial Interests, Other, Honoraria: Celgene; Financial Interests, Other, Honoraria; Travel, Accommodations, Expenses: CellCentric; Financial Interests, Other, Honoraria; Travel, Accommodations, Expenses: Daiichi Sankyo; Financial Interests, Other, Honoraria; Travel, Accommodations, Expense: Eisai; Financial Interests, Other, Honoraria; Travel, Accommodations, Expenses: Genentech/Roche; Financial Interests, Other, Honoraria; Travel, Accommodations, Expenses: Genmab; Financial Interests, Other, Honoraria; Travel, Accommodations, Expenses: GlaxoSmithKline; Financial Interests, Other, Honoraria; Travel, Accommodations, Expenses: Harpoon; Financial Interests, Other, Honoraria; Travel, Accommodations, Expenses: Janssen Oncology; Financial Interests, Other, Honoraria: Medivation; Financial Interests, Other, Honoraria; Travel, Accommodations, Expenses: Menarini Silicon Biosystems; Financial Interests, Other, Honoraria; Travel, Accommodations, Expenses: Merck Serono; Financial Interests, Other, Honoraria; Travel, Accommodations, Expenses: Merck Sharp & Dohme; Financial Interests, Other, Honoraria: Orion; Financial Interests, Other, Honoraria; Travel, Accommodations, Expenses: Pfizer; Financial Interests, Other, Honoraria; Travel, Accommodations, Expenses: Qiagen; Financial Interests, Other, Honoraria; Travel, Accommodations, Expenses: Sanofi; Financial Interests, Other, Honoraria; Travel, Accommodations, Expenses: Sierra Oncology; Financial Interests, Other, Honoraria; Travel, Accommodations, Expenses: Taiho Pharmaceutical; Financial Interests, Other, Honoraria; Travel, Accommodations, Expenses: Terumo; Financial Interests, Other, Honoraria; Travel, Accommodations, Expenses: Vertex; Financial Interests, Other, Travel, Accommodations, Expenses: Orion Pharma GmbH; Financial Interests, Advisory Role: Amgen; Financial Interests, Advisory Role: Astellas Pharma; Financial Interests, Advisory Role: AstraZeneca; Financial Interests, Advisory Role: Bayer; Financial Interests, Advisory Role: BioXCel therapeutics; Financial Interests, Advisory Role: Boehringer Ingelheim; Financial Interests, Advisory Role: CellCentric; Financial Interests, Advisory Role: Daiichi Sankyo; Financial Interests, Advisory Role: Eisai; Financial Interests, Advisory Role: Genentech/Roche; Financial Interests, Advisory Role: Genmab; Financial Interests, Advisory Role: GlaxoSmithKline; Financial Interests, Advisory Role: Harpoon; Financial Interests, Advisory Role: Janssen Oncology; Financial Interests, Advisory Role: Menarini Silicon Biosystems; Financial Interests, Advisory Role: Merck Serono; Financial Interests, Advisory Role: Merck Sharp & Dohme; Financial Interests, Advisory Role: Orion Pharma GmbH; Financial Interests, Advisory Role: Pfizer; Financial Interests, Advisory Role: Qiagen; Financial Interests, Advisory Role: Sanofi; Financial Interests, Advisory Role: Sanofi Aventis GmbH; Financial Interests, Advisory Role: Sierra Oncology; Financial Interests, Advisory Role: Taiho Pharmaceutical; Financial Interests, Advisory Role: Terumo; Financial Interests, Advisory Role: Vertex; Financial Interests, Funding: Amgen; Financial Interests, Funding: Astellas Pharma; Financial Interests, Funding: Astex Pharmaceuticals; Financial Interests, Funding: AstraZeneca; Financial Interests, Funding: Bayer; Financial Interests, Funding: CellCentric; Financial Interests, Funding: Daiichi Sankyo; Financial Interests, Funding: Genentech/Roche; Financial Interests, Funding: Genmab; Financial Interests, Funding: GlaxoSmithKline; Financial Interests, Funding: Harpoon; Financial Interests, Funding: Janssen; Financial Interests, Funding: Menarini Silicon Biosystems; Financial Interests, Funding: Merck Serono; Financial Interests, Funding: Merck Sharp & Dohme; Financial Interests, Funding: Orion Pharma GmbH; Financial Interests, Funding: Pfizer; Financial Interests, Funding: Sanofi; Financial Interests, Funding: Sanofi Aventis GmbH; Financial Interests, Funding: Sierra Oncology; Financial Interests, Funding: Taiho Pharmaceutical; Financial Interests, Funding: Vertex; Financial Interests, Institutional, Proprietary Information: Abiraterone Rewards to Inventors (Inst); CHK1 inhibitor; Financial Interests, Institutional, Proprietary Information: PARP inhibitors and DNA repair defects; Financial Interests, Institutional, Proprietary Information: Targeting of IL23 in prostate cancer. C. Sweeney: Financial Interests, Personal, Advisory Board, Consultancy: Astellas; Financial Interests, Personal, Advisory Board, Consultancy: Bayer; Financial Interests, Personal, Advisory Board, Consultancy: Genentech; Financial Interests, Personal, Advisory Board, Consultancy: Roche; Financial Interests, Personal, Other, Consultancy: Janssen; Financial Interests, Personal, Advisory Board, Consultancy: Lilly; Financial Interests, Personal, Advisory Board, Consultancy: Pfizer; Financial Interests, Personal, Advisory Board, Consultancy: Sanofi; Financial Interests, Personal, Stocks/Shares: Leuchemix; Financial Interests, Institutional, Research Grant: Astellas,; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: Dendreon; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Sanofi. K.N. Chi: Financial Interests, Other, Honoraria: Astellas Pharma; Financial Interests, Other, Honoraria: AstraZeneca; Financial Interests, Other, Honoraria: Bayer; Financial Interests, Other, Honoraria: Janssen; Financial Interests, Other, Honoraria: Merck; Financial Interests, Other, Honoraria: Roche; Financial Interests, Advisory Role: Amgen; Financial Interests, Advisory Role: Astellas Pharma; Financial Interests, Advisory Role: AstraZeneca; Financial Interests, Advisory Role: Bayer; Financial Interests, Advisory Role: Constellation Pharmaceuticals; Financial Interests, Advisory Role: Daiichi Sankyo; Financial Interests, Advisory Role: ESSA; Financial Interests, Advisory Role: Janssen; Financial Interests, Advisory Role: Merck; Financial Interests, Advisory Role: POINT Biopharma; Financial Interests, Advisory Role: Roche; Financial Interests, Advisory Role: Sanofi; Financial Interests, Institutional, Funding: Astellas Pharma; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: Bayer; Financial Interests, Institutional, Funding: Bristol-Myers Squibb; Financial Interests, Institutional, Funding: ESSA; Financial Interests, Institutional, Funding: Janssen; Financial Interests, Institutional, Funding: Merck; Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Institutional, Funding: Roche; Financial Interests, Institutional, Funding: Sanofi. D. Olmos: Financial Interests, Institutional, Other, Honoraria: Astellas Pharma; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Astellas Pharma; Financial Interests, Other, Honoraria; Travel, Accommodations, Expenses: Bayer; Financial Interests, Other, Honoraria; Travel, Accommodations, Expenses: Janssen; Financial Interests, Other, Travel, Accommodations, Expenses: Ipsen; Financial Interests, Other, Travel, Accommodations, Expenses: Roche; Financial Interests, Institutional, Advisory Role: AstraZeneca; Financial Interests, Personal and Institutional, Advisory Role: Bayer; Financial Interests, Advisory Role: Clovis Oncology; Financial Interests, Advisory Role: Daiichi Sankyo; Financial Interests, Personal and Institutional, Advisory Role: Janssen; Financial Interests, Advisory Role: MSD Oncology; Financial Interests, Institutional, Funding: Astellas Medivation; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: Bayer; Financial Interests, Institutional, Funding: Genentech/Roche; Financial Interests, Institutional, Funding: Janssen; Financial Interests, Institutional, Funding: MSD Oncology; Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Institutional, Funding: Tokai Pharmaceuticals. S.K. Sandhu: Financial Interests, Institutional, Other, Honoraria: AstraZeneca; Financial Interests, Institutional, Other, Honoraria: Bristol-Myers Squibb; Financial Interests, Institutional, Other, Honoraria: Merck; Financial Interests, Institutional, Other, Honoraria: Merck Serono; Financial Interests, Other, Travel, Accommodations, Expenses: Roche/Genentech; Financial Interests, Advisory Role: Amgen; Financial Interests, Speaker’s Bureau: Bristol-Myers Squibb; Financial Interests, Speaker’s Bureau: Merck; Financial Interests, Speaker’s Bureau: Roche/Genentech; Financial Interests, Institutional, Funding: Amgen; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: Bristol-Myers Squibb; Financial Interests, Institutional, Funding: Endocyte/Advanced Accelerator Applications; Financial Interests, Institutional, Funding: Genentech/Roche; Financial Interests, Institutional, Funding: Merck. C. Massard: Financial Interests, Advisory Role: Amgen; Financial Interests, Advisory Role: Astellas Pharma; Financial Interests, Advisory Role: AstraZeneca; Financial Interests, Advisory Role: Bayer; Financial Interests, Advisory Role: BeiGene; Financial Interests, Advisory Role: Blueprint Medicines; Financial Interests, Advisory Role: Bristol-Myers Squibb; Financial Interests, Advisory Role: Celgene; Financial Interests, Advisory Role: Debiopharm Group; Financial Interests, Advisory Role: Genentech/Roche; Financial Interests, Advisory Role: Innate Pharma; Financial Interests, Advisory Role: Ipsen; Financial Interests, Advisory Role: Janssen; Financial Interests, Advisory Role: Lilly; Financial Interests, Advisory Role: MSD; Financial Interests, Advisory Role: Novartis; Financial Interests, Advisory Role: Orion; Financial Interests, Advisory Role: Pfizer; Financial Interests, Advisory Role: PharmaMar; Financial Interests, Advisory Role: Sanofi; Financial Interests, Advisory Role: Taiho Pharmaceutical. J. Garcia: Financial Interests, Personal, Full or part-time Employment: Roche. F. Schenkel: Financial Interests, Personal, Full or part-time Employment: Roche. G. Chen: Financial Interests, Personal, Full or part-time Employment: Genentech; Financial Interests, Personal, Stocks/Shares: Genentech. A. Harris: Financial Interests, Personal, Full or part-time Employment: Genentech. H. Hinton: Financial Interests, Personal, Full or part-time Employment: Roche. N. Matsubara: Financial Interests, Advisory Role: Janssen; Financial Interests, Advisory Role: Sanofi; Financial Interests, Advisory Role: AstraZeneca; Financial Interests, Advisory Role: Roche; Financial Interests, Speaker’s Bureau: Janssen; Financial Interests, Speaker’s Bureau: Sanofi; Financial Interests, Institutional, Funding: Janssen; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: Takeda; Financial Interests, Institutional, Funding: Lilly; Financial Interests, Institutional, Funding: Amgen; Financial Interests, Institutional, Funding: Astellas; Financial Interests, Institutional, Funding: Chugai; Financial Interests, Institutional, Funding: Bayer; Financial Interests, Institutional, Funding: MSD; Financial Interests, Institutional, Funding: Ono; Financial Interests, Institutional, Funding: Taiho; Financial Interests, Institutional, Funding: Pfizer.