Abstract P6-13-05: Impact of olaparib versus chemotherapy on the use of strong pain medications in gBRCA-mutated HER2-negative metastatic breast cancer and associated patient reported outcomes
Authors: Merens Chantal , Bannister Wendy , Bergner Sven , Hettle Robert , McCrea Charles , McCutcheon Susan , Degboe Arnold 
Published: March 2020

Abstract
Background: Pain is among the most common and distressing symptoms in patients with cancer, frequently requiring treatment with strong pain medication (SPM). The use of SPM may be associated with an adverse health impact arising from SPM-mediated side effects and/or the underlying deterioration causing SPM use. Regardless of cause, delaying the need for or escalation in SPM use would be desirable. The primary aim of this post-hoc analysis was to assess the impact of olaparib on SPM use compared with chemotherapy treatment of physician’s choice (TPC) in patients with gBRCA-mutated HER2-negative metastatic breast cancer in the OlympiAD study (NCT02000622). Further exploratory analyses were performed to understand the association between SPM use and patient-reported outcomes (PRO). Methods: Data on the first use and dose increase in commonly prescribed SPMs, including opioid analgesics and anesthetics, were obtained from concomitant medication data routinely collected up to 30 days post-discontinuation of study drug in OlympiAD. The impact of study treatment on SPM use was assessed using the time from randomization to on-treatment initiation/dose increase of SPMs. The association between SPM use and PRO were assessed via a mixed-model for repeated measures analysis of EORTC QLQ-C30 data, routinely collected up to RECIST progression, with covariates for treatment, and pre- versus post-initiation or increase in SPMs. Differences in the association between SPMs and PRO, and randomized treatment were assessed via an interaction term. All analyses were performed on the full analysis set of the OlympiAD study. Results: 29.3% of olaparib patients and 30.9% of TPC patients had an on-treatment initiation/dose increase in SPMs during study follow-up. The hazard ratio of the time to on-treatment initiation/dose increase in SPMs comparing olaparib with TPC was 0.55 (95% confidence interval 0.33, 0.90; nominal P=0.0174); 77.2% in the olaparib arm and 66.2% in the TPC arm were event free at 6 months. The mean difference in PRO scores comparing post- versus pre-SPM periods across both study arms are presented in Table 1. For all but one of the EORTC scales, there was no statistical evidence of a difference in mean scores by SPM period according to randomized group. For social functioning, TPC patients experienced a -14.9 (-24.82, -5.07; P=0.0031) point change in the post- versus pre-SPM period, compared with 0.6 (-5.39, 4.22; P=0.8104) for olaparib.
Table 1: Mean difference in EORTC QLQ-C30 scales (all randomized patients in OlympiAD)EORTC QLQ-C30 ScaleMean difference post vs pre-SPM (95% CIs; nominal P value)Global health status-3.7 (-8.73; 1.42; P=0.1576)Functioning (decrease equates to worsening)Physical-4.6 (-8.03; -1.08; P=0.0103)Role-7.6 (-13.25; -1.92; P=0.0088)Emotional-4.3 (-8.72; 0.14; P=0.0580)Cognitive-2.4 (-6.72; 2.01; P=0.2894)Social-7.8 (-13.28; -2.25; P=0.0059)Symptoms (increase equates to worsening)Fatigue3.9 (-1.17; 9.05; P=0.1306)Pain6.7 (1.25; 12.23; P=0.0163)Nausea/vomiting4.1 (0.56; 7.69; P=0.0233)Dyspnea4.3 (-1.28; 9.92; P=0.1300)Appetite loss6.3 (0.33; 12.36; P=0.0386)Insomnia2.2 (-3.96; 8.34; P=0.4848)Constipation4.5 (-0.54; 9.57; P=0.0796)Diarrhea-2.9 (-7.37; 1.49; P=0.1935)Financial difficulties5.7 (-0.23; 11.70; P=0.0597)
Conclusions: Olaparib appears associated with a delay in the use of, or escalation in, SPM versus TPC. Across study arms, SPM use was associated with a decrement in EORTC QLQ-C30 pain score, as well as worsening in role, physical and social functioning, and symptoms of appetite loss, and nausea and vomiting. These results support the relevance of SPM as an indicator of deterioration in PRO. Further research on the impact of SPM on PRO in breast cancer is required.
Citation Format: Chantal Merens, Wendy Bannister, Sven Bergner, Robert Hettle, Charles McCrea, Susan McCutcheon, Arnold Degboe. Impact of olaparib versus chemotherapy on the use of strong pain medications in gBRCA-mutated HER2-negative metastatic breast cancer and associated patient reported outcomes [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-13-05.