Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Gynaecological cancers

5384 - Disruptive mutations in TP53 associate with survival benefit in a PARPi trial in Ovarian Cancer

Date

09 Sep 2017

Session

Gynaecological cancers

Topics

Cytotoxic Therapy;  Translational Research;  Ovarian Cancer

Presenters

Alejandro Martinez Bueno

Citation

Annals of Oncology (2017) 28 (suppl_5): v605-v649. 10.1093/annonc/mdx440

Authors

A. Martinez Bueno1, M.A. Molina2, A. Fielding3, J. Bertran-Alamillo2, B.A. Dougherty4, Z. Lai4, D. Hodgson3, C. Mayo de las Casas2, P. Rowe3, M. Gil1, S. Spencer5, S. Viteri1, J. Lobera6, R. Rosell7, A. Gasco Hernandez8

Author affiliations

  • 1 Medical Oncology, I. O. Rosell- H Quirón Dexeus, 08028 - BARCELONA/ES
  • 2 Laboratory Of Oncology-pangaea Oncology, H. Quirón Dexeus, 08028 - BARCELONA/ES
  • 3 Oncology, Astrazeneca, SK10 4TG - Macclesfield/GB
  • 4 Oncology, AstraZeneca, Waltham/US
  • 5 Oncology, AstraZeneca, Cambridge/GB
  • 6 Oncology, AstraZeneca Spain, 28033 - Madrid/ES
  • 7 Oncology, Institute of Oncology Dr. Rosell (Dexeus University Hospital QuironSalud Group), 80280 - Barcelona/ES
  • 8 Oncology Global Medical Affairs, AstraZeneca, Cambridge/GB
More

Resources

Abstract 5384

Background

Olaparib is a PARP inhibitor approved in Europe as maintenance treatment after response to platinum-based chemotherapy in patients (pts) with relapsed, epithelial ovarian cancer (EOC) who harbour a mutation in BRCA. Approval was based on the results of study 19 (NCT00753545). We tested whether TP53 mutations categorized according to their functional effects influence overall survival (OS) in a cohort of 195 EOC pts randomized to olaparib or placebo after platinum-based chemotherapy in study 19.

Methods

TP53 status was assessed in anonymized archival tumor samples at Foundation Medicine.TP53 mutations were classified, blinded to treatment and clinical outcome, as “disruptive” (D) and “non disruptive” (ND) according to the degree of disturbance of p53 protein function and structure. Particularly, TP53 (D) mutations are associated with a severe disturbance in the DNA repair activities of the p53 protein. Overall survival (OS) and progression-free survival (PFS) were explored by TP53 and BRCA mutation status. Data cut-off was May 2016.

Results

95 pts had TP53(D) and 100 pts TP53(ND) tumours. Hazard ratios (HR) for PFS in the overall, BRCAm and BRCAwt populations were comparable between TP53(D) and TP53(ND). Pts with TP53(D) derived a statistically significant benefit from olaparib treatment, with median OS of 39.5 months (m) for olaparib and 24.0 m for placebo and a HR = 0.57 (95%CI = [0.35, 0.92]) versus HR = 0.73 (95%CI = [0.46, 1.15]) in the case of pts with TP53(ND). When including BRCA status in the analysis; all pts with BRCA mutations (n = 108) derived a benefit from olaparib in terms of OS, irrespective of TP53 status. In the BRCA wt group, pts with TP53(D) treated with olaparib had an OS of 35.0 m vs. 25.5 m for those receiving placebo (n = 47, HR = 0.80 [0.40, 1.52]). Finally, only pts with TP53(ND) and BRCAwt did not derive any benefit in median OS from olaparib treatment (n = 40, HR = 1.58 [0.77, 3.35]).

Conclusions

EOC patients BRCA wt with TP53 disruptive mutations may derive a survival benefit of olaparib treatment. Further studies are required to confirm this finding.

Clinical trial identification

Legal entity responsible for the study

Instituto Oncologico Dr Rosell. Astra Zeneca

Funding

None

Disclosure

A. Fielding, B.A. Dougherty, Z. Lai, D. Hodgson, P. Rowe, S. Spencer, A. Gasco Hernandez: Astra Zeneca employee J. Lobera: Astra Zeneca All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.