Abstract GS4-09: Quality of life results from OlympiA: A phase III, multicenter, randomized, placebo-controlled trial of adjuvant olaparib after (neo)-adjuvant chemotherapy in patients with germline BRCA1/2 mutations and high-risk HER-2 negative early breast cancer

Abstract

Abstract Background: The primary results from the OlympiA trial were recently reported (NEJM, 2021) after an interim analysis demonstrated statistically significant invasive disease-free survival (DFS) benefit from 1 year of olaparib (OL) vs. placebo (PL) after 2.5 yrs median follow-up. Although there were fewer deaths with OL than PL, overall survival (OS) did not reach the statistical significance threshold prespecified for interim analysis. The initial publication also reported on the adverse event profile, which was similar to that previously reported, as well as Global Health Status/Quality of Life (GHQ), a secondary endpoint for the Patient-Reported Outcome (PRO) sub-study. The full protocol-specified PRO analyses are presented here. Methods: The OlympiA randomized phase III trial (NCT02032823, BIG 6-13, NSABP B-55) tested the role of 1 year of adjuvant OL after completion of (neo)adjuvant chemotherapy and definitive local therapy on invasive DFS, distant DFS and OS, and sought to collect PRO data from all eligible patients (pts) prior to randomization, on treatment (trt) (6 and 12 months [mos]), and after trt (18 and 24 mos) using validated questionnaires available in multiple languages. Fatigue, the primary PRO endpoint, was measured with the FACIT-Fatigue Scale in which a clinically meaningful (CM) difference is ≥3 points. Secondary PRO endpoints included gastrointestinal (GI) symptoms (nausea and vomiting [NV], diarrhea) and multiple quality of life (QOL) domains assessed with the EORTC QLQ-C-30 questionnaire (CM differences: small 5-10 points, moderate 10-20 points [Osoba, 1998]). The primary protocol-specified PRO hypothesis was that during trt pts treated with OL may experience greater fatigue severity at 6 and 12 mos. Secondary PRO hypotheses included: a) pts receiving OL may experience greater severity of GI symptoms at 6 and 12 mos with no difference by 24 mos; b) no difference in fatigue severity post-trt at 18 and 24 mos; and c) no difference in QOL over duration of the PRO sub-study between OL and PL as measured by the GHQ score and other EORTC QLQ-C30 subscales. A mixed model for repeated measures analysis compared the primary and secondary endpoints scores. Separate analyses were performed for neoadjuvant (NAC) and adjuvant (AC) chemotherapy subgroups due to differences in interval from NAC and AC to randomization. Two-sided p-values <0.05 were considered statistically significant. Results: Of 1,836 randomized pts, 1,751 (NAC: 875 [OL:440, PL: 435], AC: 876 [OL:436, PL:440]) were included in the PRO sub-study. Baseline QOL and symptom scores did not differ between OL and PL. Fatigue severity was statistically significantly greater in pts treated with OL than with PL at 6 mos (diff OL vs. PL: NAC -1.3 [95%CI -2.4, -0.2], p=0.024; AC -1.3 [-2.3,-0.2], p=0.017) and 12 mos (NAC -1.5 [-2.8,-0.2] p=0.025; AC -1.3 [-2.4,-0.1] p=0.027); however, the differences did not meet the pre-specified criterion for CM with the FACIT-Fatigue Scale. There were no meaningful differences in fatigue severity at 18 and 24 mos. NV symptom severity was worse in pts treated with OL than with PL with small differences at 6 mos (NAC: 6.0 [4.0, 8.0], p<0.001, AC: 5.3 [3.4,7.2], p<0.001) and 12 mos (NAC: 6.3 [4.4, 8.2], p<0.001, AC: 4.5 [2.8,6.2], p<0.001), and no differences at 18 and 24 mos. In general, there were no CM differences between OL and PL in terms of other symptoms and QOL subscales with improvements in functioning over time. Conclusions: Increased trt-emergent symptoms with OL were small and resolved after trt. QOL scores were similar and slowly improved during the 24 mos after (neo) adjuvant chemotherapy. Support: U10CA180868, -180822, UG1CA189867, AstraZeneca, Merck and Co, Inc. NCT02032823 Citation Format: Patricia A Ganz, Hanna Bandos, Tanja Spanic, Sue Friedman, Volkmar Müller, Sherko Kümmel, Suzette Delaloge, Etienne Brain, Masakazu Toi, Hideko Yamauchi, Eduardo-Martínez de Dueñas, Anne Armstrong, Seock-Ah Im, Chuangui Song, Hong Zheng, Tomasz Sarosiek, Priyanka Sharma, Giovanna Rossi, Priya Rastogi, Anitra Fielding, Richard D Gelber, Christine Campbell, Judy E Garber, Charles E Geyer, Jr, Andrew NJ Tutt, On behalf of the OlympiA Trial Steering Committeeand Investigators. Quality of life results from OlympiA: A phase III, multicenter, randomized, placebo-controlled trial of adjuvant olaparib after (neo)-adjuvant chemotherapy in patients with germline BRCA1/2 mutations and high-risk HER-2 negative early breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr GS4-09.