LBA25 - Olaparib in combination with paclitaxel in patients with advanced gastric cancer who have progressed following first-line therapy: Phase III GOLD s...

Date 08 October 2016
Event ESMO 2016 Congress
Session Gastrointestinal tumours, non-colorectal 1
Topics Anti-Cancer Agents & Biologic Therapy
Gastric Cancer
Presenter Yung-Jue Bang
Citation Annals of Oncology (2016) 27 (6): 1-36. 10.1093/annonc/mdw435
Authors Y. Bang1, N. Boku2, K. Chin3, K. Lee4, S.H. Park5, S. Qin6, S.Y. Rha7, L. Shen8, N. Xu9, S. Im1, G. Locker10, P. Rowe11, X. Shi12, D. Hodgson13, Y. Liu14, R. Xu15
  • 1Department Of Internal Medicine, Seoul National University Hospital (SNUH)-Yongon Campus, 110-744 - Seoul/KR
  • 2Department Of Gastroenterology, St. Marianna University School of Medicine, Kawasaki/JP
  • 3Department Of Gastroenterology, Cancer Institute Hospital of JFCR, 135-8550 - Tokyo/JP
  • 4Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 13620 - Seongnam/KR
  • 5Medicine, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul/KR
  • 6Medical Oncology, Nanjing Bayi Hospital, 210002 - Nanjing/CN
  • 7Medical Oncology, Internal Medicine, Yonsei Severance Hospital Cancer Center, (120-752) - Seoul/KR
  • 8Gi Oncology, Peking University Cancer Hospital-Beijing Cancer Hospital, Beijing/CN
  • 9Department Of Medical Oncology, 1st Affiliated Hospital of Zhejiang University School of Medicine, 310003 - Hangzhou/CN
  • 10Clinical Research, AstraZeneca, Gaithersburg/US
  • 11Pharmaceutical And Analytical R&d, AstraZeneca, Macclesfield/GB
  • 12Global R&d, AstraZeneca, Shanghai/CN
  • 13Oncology Translational Science, AstraZeneca, SK10 4TG - Macclesfield/GB
  • 14Personalised Healthcare & Biomarkers, AstraZeneca, Cambridge/GB
  • 15Medical Oncology, Cancer Centre Sun Yat-Sen University, 510060 - Guangzhou/CN

Abstract

Background

A Phase II study (Study 39, D0810C00039; NCT01063517) showed that the oral PARP inhibitor olaparib (Lynparza) combined with paclitaxel provided a statistically significant improvement in overall survival (OS) versus paclitaxel alone as second-line therapy in Asian patients (pts) with advanced gastric cancer. A greater OS benefit was seen in pts whose tumour was ATM protein negative by immunochemistry (ATM–). ATM is a key sensor of the DNA damage response pathway. We report final analyses from a subsequent Phase III study (GOLD, D081BC00004; NCT01924533). GOLD evaluated the efficacy and safety of olaparib (100 mg tablet bid, continuous) in combination with paclitaxel (80 mg/m2 iv on days 1, 8, 15 per 28-day cycle) (O/P) compared with placebo in combination with paclitaxel (P/P).

Methods

Pts were randomized 1:1 to O/P or P/P and treated until progression (RECIST 1.1), unmanageable toxicity or consent withdrawal. On discontinuation of paclitaxel (without progression), olaparib (300 mg bid) or placebo was given as monotherapy. The co-primary endpoints were OS for all pts (full analysis set [FAS]) and ATM– pts. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR) and safety.

Results

521/525 randomized pts were treated (O/P = 261; P/P = 260), including 93/94 ATM– pts (O/P = 47; P/P = 46).

O/P P/P
All pts (FAS) (72.6% OS maturity) N = 263 N = 262
Median OS, months 8.8 6.9 HR = 0.79; 97.5% CI 0.63, 1.00; P = 0.0262
Median PFS, months 3.7 3.2 HR = 0.84; 97.5% CI 0.67, 1.04; P = 0.0645
Adjusted ORR,* % 24.0 15.8 OR = 1.69; 97.5% CI 0.92, 3.17; P = 0.0548
ATM– pts (68.1% OS maturity) n = 48 n = 46
Median OS, months 12.0 10.0 HR = 0.73; 97.5% CI 0.40, 1.34; P = 0.2458
Median PFS, months 5.3 3.7 HR = 0.74; 97.5% CI 0.45, 1.29; P = 0.2199
Adjusted ORR,* % 37.5 16.1 OR = 4.24; 97.5% CI 0.95, 23.23; P = 0.0309

Due to Hochberg multiple testing procedure, statistical significance was P < 0.025 for each population *Response rate in pts with measurable disease only CI, confidence interval; HR, hazard ratio; OR, odds ratio HR 1 favours O/P; P values are two sided.

In the O/P and P/P arms, respectively, grade ≥3 adverse events (AEs) were reported in 78% and 62% of pts, most frequently neutropenia (30% vs 23%). Serious AEs were reported in 35% and 25% of pts, and AEs leading to discontinuation occurred in 16% and 10% of pts.

Conclusions

A trend towards OS benefit, independent of ATM status, was observed for O/P compared with P/P in the FAS. O/P did not provide statistically significant increased OS, PFS or ORR in the FAS or ATM– pts compared with P/P. O/P followed by olaparib monotherapy was well tolerated with no new safety signals.

Clinical trial identification

D081BC00004; NCT01924533 2 May 2013

Legal entity responsible for the study

AstraZeneca

Funding

AstraZeneca

Disclosure

Y-J. Bang: I received research funds from AstraZeneca (through my institution), and I have consulted AstraZeneca. L. Shen: Personal fees received from: Hengrui Taiho Roche Novartis. S-A. Im: Research grant from AstraZeneca. G. Locker, X. Shi, D. Hodgson, Y-Z. Liu: AstraZeneca employee and own AstraZeneca stock. P. Rowe: AstraZeneca. All other authors have declared no conflicts of interest.