Patients with Advanced FIGO Stage IIIB IV High Grade Serous or - - PowerPoint PPT Presentation

PAOLA-1 : Randomized, Double-Blind, Phase III Trial of Olaparib vs. Placebo in Patients with Advanced FIGO Stage IIIB – IV High Grade Serous or Endometrioid Ovarian, Fallopian Tube,

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Peritoneal Cancer treated with standard First-Line Treatment, Combining Platinum-Taxane Chemotherapy and Bevacizumab Concurrent with Chemotherapy and in Maintenance Sponsor: ARCAGY Research (for GINECO) Principal Investigator: Prof. Isabelle RAY-COQUARD Centre Léon BERARD, Lyon, France

PAOLA-1 Study Planned No. of patients: 762 (=612 +150) +24 in Japan Current accrual: 682 (15/05/17)

PAOLA-1 Study: new statistical hypothesis

❖ New data on PARPi efficacy in maintenance have been recently disclosed in NOVA trial5 and stressed the importance of the tumor homologous recombination deficiency (HRD) in the efficacy of PARPi in ovarian carcinoma. ❖As in the NOVA trial the magnitude of PARPi efficacy for patients with HRD negative tumors was found to be small, it is assumed that in the PAOLA-1 trial, the potential benefit of olaparib will be driven mainly by the BRCAm & HRD positive subset (representing approximately 55% of the total population). ❖Given these considerations, the planned sample size seems to be underpowered to detect a significant difference in ITT with an assumed control median PFS population. ❖ The new calculation has taken into account the expected different levels of benefit according to the patient subsets and they were applied in deriving an appropriate sample size.of 15.8 months and a HR of 0.75 in the ITT population, a total of 458 events would have the adequate power (> 80%) to show a statistically significant difference PFS1 between the 2 arms at a 2-sided alpha. ❖Interim analysis will be performed for efficacy after 229 events (50% PFS1). ❖The sample size has been increased by 150 patients in Europe (100 in the olaparib arm and 50 patients in the placebo arm) up to 762 patients maintaining 60% maturity.

PAOLA-1 status (15/05/2017)

Expected end of recruitment July 2017

100 200 300 400 500 600 700 800 Number of patients

Accrual

Theorical randomization curve Real curve

682

1194 682 100 200 300 400 500 600 700 800 900 1000 1100 1200 1300 Number of patients

Global recruitment

Screened patients Randomized patients 496 398 88 74 42 26 29 20 19 281 219 52 47 23 24 15 11 8 100 200 300 400 500 600 Registred pts Randomized pts 1 5 8 9 11 7 14 10 20 15 14 17 13 18 18 12 21 17 13 13 13 9 2 1 1 3 7 9 16 14 15 13 13 13 16 26 15 18 8 19 8 3 1 2 1 2 1 3 1 0 1 2 1 1 1 2 2 1 0 3 2 4 1 2 2 1 4 1 2 3 5 10 5 6 2 2 2 2 2 4 2 3 4 1 2 2 1 3 1 3 5 3 4 6 3 4 3 4 6 1 10 20 30 40 50 60 70

Randomizations per month

NSGO MANGO GEICO GOTIC MITO AGO Aust BGOG AGO De