885PD - Health-related quality of life (HRQoL) during olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer (PSR...

Date 28 September 2014
Event ESMO 2014
Session Gynaecological cancers
Topics Ovarian Cancer
Psychosocial Aspects of Cancer
Pathology/Molecular Biology
Presenter Jonathan Ledermann
Citation Annals of Oncology (2014) 25 (suppl_4): iv305-iv326. 10.1093/annonc/mdu338
Authors J.A. Ledermann1, P. Harter2, C. Gourley3, M. Friedlander4, I.B. Vergote5, G.J.S. Rustin6, C. Scott7, W. Meier8, R. Shapira-Frommer9, T. Safra10, D.E. Matei11, A. Fielding12, S. Spencer12, B. Bennett12, D. Parry12, U. Matulonis13
  • 1Cancer Research Uk And Ucl Cancer Trials Centre, University College London Cancer Institute, WC1E6BT - London/GB
  • 2Dept Gynecology & Gyn.oncology, Kliniken Essen-Mitte, Essen/DE
  • 3Mrc Institute Of Genetics And Molecular Medicine, Edinburgh Cancer Research UK Centre, EH4 2XR - Edinburgh/GB
  • 4University Of New South Wales, Prince of Wales Clinical School, Sydney/AU
  • 5Obstetrics & Gynaecology, University Hospitals Leuven - Campus Gasthuisberg, 3000 - Leuven/BE
  • 6Medical Oncology, Mount Vernon Cancer Centre, GB-HA6 2RN - Northwood/GB
  • 7., Royal Melbourne Hospital, Melbourne/AU
  • 8Dept. Of Gynecology, Evangelisches Krankenhaus, Düsseldorf/DE
  • 9., Chaim Sheba Medical Center, Tel Hashomer/IL
  • 10., Tel Aviv Sourasky Medical Center, Tel Aviv/IL
  • 11Medicine, Indiana University, Indianapolis/US
  • 12Research And Development, AstraZeneca, Macclesfield/GB
  • 13Gynecology, Dana Farber Cancer Institute, 02115 - Boston/US

Abstract

Aim

Maintenance monotherapy with the PARP inhibitor olaparib significantly prolonged progression-free survival (PFS) versus placebo in patients with PSR SOC, and subsequent analysis has shown that patients with a BRCAm receive greater treatment benefit (Ledermann et al Lancet Oncol 2014). As preserved HRQoL may support chronic administration in the maintenance setting, the effect of olaparib on HRQoL was evaluated in this randomized, double-blind Phase II trial (NCT00753545).

Methods

Patient-reported HRQoL and disease-related symptoms were evaluated using the Functional Assessment of Cancer Therapy Ovarian (FACT-O) questionnaire, FACT/NCCN Ovarian Symptom Index (FOSI) and Trial Outcome Index (TOI). Patients completed the FACT-O questionnaire at baseline and every 28 days until progression. Individual symptom severity over 7 days was measured using the five-item Likert scale; physical, social/family, emotional, functional wellbeing and specific concerns to ovarian cancer patients were assessed. The TOI of the FACT-O was the primary HRQoL endpoint. FOSI is the sum of a subset of eight symptom-related items.

Results

Of patients randomized to olaparib (n = 136) or placebo (n = 129), BRCA mutation status data were available for 254/265 (96%), of whom 136/254 (53.5%) had a known deleterious/suspected deleterious germline or somatic BRCA mutation. Most patients reported a best response of ‘improved’ or ‘no change’ on TOI (Table); this trend was also seen in other HRQoL measures. There were no statistically significant differences in improvement rates or time to worsening of TOI, FOSI and Total FACT-O.

Overall BRCAm BRCAwt
Olaparib Placebo Olaparib Placebo Olaparib Placebo
TOI N = 115 N = 111 N = 64 N = 53 N = 49 N = 54
Improved* 23 (20.0) 20 (18.0) 16 (25.0) 10 (18.9) 7 (14.3) 10 (18.5)
No change 72 (62.6) 67 (60.4) 38 (59.4) 30 (56.6) 32 (65.3) 36 (66.7)
Worsened†† 16 (13.9) 20 (18.0) 7 (10.9) 10 (18.9) 9 (18.4) 8 (14.8)
Non-evaluable 4 (3.5) 4 (3.6) 3 (4.7) 3 (5.7) 1 (2.0) 0

*Best response of improved defined as two visit responses of 'improved' a minimum of 21 days apart without an intervening visit response of 'worsened'. Defined as two visit responses of 'no change' or a response of 'no change' and a response of 'improved' a minimum of 21 days apart without an intervening visit response of 'worsened'. No change is defined as a change from baseline of greater than -7 but less than +7. ††Defined as a visit of 'worsened' without a response of 'improved' or 'no change' within 21 days. Worsened is defined as a change from baseline of less than or equal to -7.

BRCAwt, BRCA wild type, includes patients with no known BRCAm or a variant of unknown significance.

Conclusions

HRQoL was not negatively impacted during maintenance therapy with olaparib. Phase III trials are enrolling.

Disclosure

J.A. Ledermann: Travel grants from AstraZeneca; P. Harter: Received a grant from AstraZeneca; C. Gourley: Served on advisory boards for, and received travel grants from, AstraZeneca; G.J.S. Rustin: Served on advisory boards for AstraZeneca, Oxigene, Roche, Amgen, Boehringer Ingelheim and Clovis; C. Scott: Received travel grants from AstraZeneca; A. Fielding, S. Spencer, B. Bennett and D. Parry: Employee of AstraZeneca and stock ownership. All other authors have declared no conflicts of interest.