AstraZeneca Investor Day Presentation Deck slide image

AstraZeneca Investor Day Presentation Deck

Lynparza and abiraterone Success in Study 08 paved the way for PROpel in 1st-line mCRPC Radiographic progression-free survival (%) 100- 80- 60- 40- 20- Number at risk (number censored) Olaparib and abiraterone 71 (0) Placebo and abiraterone 71 (0) Study 08¹ Phase II trial T6 9 58 (5) 50 (6) 42 (8) 48 (3) 39 (4) 25 (5) 12 15 - Olaparib and abiraterone (n=71) -Placebo and abiraterone (n=71) HR 0-65 (95% CI 0-44-0-97); p=0-034 18 21 24 33 (9) 26 (12) 21 (13) 18 (13) 13 (17) 8 (19) 0 (25) 21 (7) 19 (7) 16 (7) 14 (7) 10 (8) 7 (10) 0 (17) 35% risk reduction Significant rPFS benefit regardless of HRRm status PARP-signaling and AR-signaling pathway interaction may explain combined effect Lynparza + abiraterone²-4 PARP involved in androgen- receptor-dependent transcription; PARP inhibition may increase activity of NHAs² NHA-induced HRR deficiency increasing susceptibility to PARP inhibition 3,4 Combined effect Antitumour activity in HRRm and non- HRRm prostate cancer²-4 8 1. Saad et al Lancet Oncol 2018; 19: 975-86 2. Schiewer MJ, et al. Cancer Discov. 2012;2:1134-1149 3. Polkinghorn WR, et al. Cancer Discov. 2013;3:1245-12534. Asim M, et al. Nat Commun. 2017;8(1):374. rPFS = radiographic progression free survival; HRR = homologous recombination repair; HRRm = HRR gene mutation; PARP = poly adenosine diphosphate-ribose polymerase; AR = androgen receptor; NHA = new hormonal agents.
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