Title: OlympiAD: Health-related quality of life (HRQoL) in patients with HER2-negative metastatic breast cancer (mBC) and a germline BRCA mutation (gBRCAm) receiving olaparib monotherapy vs standard single-agent chemotherapy treatment of physician’s choice (TPC)
Abstract: Background: The Phase III OlympiAD study showed a statistically significant and clinically meaningful PFS survival benefit with olaparib monotherapy, compared with standard of care chemotherapy (median 7.0 vs 4.2 months, respectively, hazard ratio 0.58; 95% CI 0.43, 0.80; P = 0.0009) in patients (pts) with HER2-negative mBC and a gBRCAm. A key predefined secondary objective was to assess the effect of olaparib on HRQoL. Methods: The randomized, open-label, Phase III OlympiAD study (NCT02000622) enrolled pts with HER2-negative mBC and a gBRCAm, after ≤2 chemotherapy lines for mBC. Pts were randomized 2:1 to olaparib tablets (300 mg bid) or single-agent treatment of physician’s choice (TPC; capecitabine, vinorelbine or eribulin). Pts were asked to complete an EORTC QLQ-C30 questionnaire (analysis focused on the Global HRQoL scale with range 0–100, and higher scores indicating a better QoL), at baseline and every 6 weeks until disease progression. Changes in Global HRQoL scores were analyzed descriptively, and mean change from baseline (cfb) by a mixed model for repeated measures. Results: 302 pts (ITT) were randomized to olaparib (n = 205) or TPC (n = 97). Overall QLQ-C30 compliance rate was 93% for olaparib vs 77% for TPC. HRQoL was better preserved with olaparib than TPC (mean cfb in Global HRQoL score across all visits was 3.9 [n = 191] vs -3.6 [n = 73], respectively, difference 7.5; 95% CI 2.48, 12.44; P=0.0035). The proportion of pts (ITT) who were free of Global HRQoL deterioration (cfb decrease in ≥ 10 points) was 81.5% in the olaparib arm vs 61.2% in the TPC arm at 6 months, and 64.0% vs 53.5% at 12 months, respectively. The median time to Global HRQoL deterioration was not reached in olaparib pts, and was 15.3 months for TPC pts. A best HRQoL response of ‘improved’ (cfb increase in ≥ 10 points over two visits ≥21 days apart) was observed in 34% olaparib pts vs 13% TPC. Conclusions: Pts receiving olaparib experienced significantly less and later deterioration in Global HRQoL vs TPC. HRQoL was modestly and consistently greater in patients receiving olaparib compared with TPC. Clinical trial identification: Clinical trials no: NCT02000622 Release date: 18 November 2013 AstraZeneca name: OlympiAD AstraZeneca number: D0819C00003. Legal entity responsible for the study: AstraZeneca Funding: AstraZeneca Disclosure: M. Robson: Consultancy: AstraZeneca and McKesson. Travel, accommodation and expenses and honoraria: AstraZeneca. Research funding: AstraZeneca, AbbVie, Myriad Genetics and Medivation. S-A. Im: Research grant from AstraZeneca. E. Senkus-Konefka: Honoraria, Consulting/Advisory: Amgen, AstraZeneca, Pfizer, Pierre Fabre, Roche. Travel, accommodation, expenses: Amgen, AstraZeneca, Pfizer, Novartis, Roche. S.M. Domchek: Honorarium from EMD Serrano.The University of Pennsylvania has received research funding from AbbVie and Clovis. N. Masuda: Personal honoraria from: Chugai Pharma and AstraZeneca. Institution research funding from: Chugai Pharma, AstraZeneca, Kyowa Hakka Kirin, MSD, Novartis, Pfizer and Lilly. S. Delaloge: AstraZeneca advisory board member, and institution funded for sponsored research from AstraZeneca. N. Tung: Research funding from Myriad and Ambry. A. Armstrong: Consulting/advisory: Roche, Syndax. W. Wu, C. Goessl, A. Degboe: AstraZeneca employee with stocks. P.F. Conte: Speakers' bureau and advisory board: AstraZeneca. All other authors have declared no conflicts of interest.