Data source and study design
Data were obtained from the Adelphi Real World Advanced Breast Cancer Disease Specific Programmes™ (DSP; Bollington, UK) conducted from October 2019 through March 2020 in the United States, France, Germany, Italy, Spain, and Israel. Disease Specific Programmes are large, multinational, point-in-time surveys of physicians and their patients presenting in a real-world clinical setting that assess disease management, disease burden, and associated treatment effects [10].
Medical oncologists treating ≥5 patients with ABC per month and actively involved in patient prescribing decisions were recruited by local fieldwork teams. Physicians provided patient record forms for 8 eligible patients: 4 patients receiving first-line advanced treatment and 4 patients receiving second- or later-line advanced treatment. Eligible patients were aged ≥18 years with stage IIIb or IV HER2− breast cancer, receiving therapy for ABC at the time of data collection, and not currently participating in a clinical trial. Physicians were invited to complete 1 to 4 patient record forms (PRFs) regarding patients with known somatic or germline BRCA1/2muts who fit the overall eligibility criteria. Only patients with known gBRCA1/2muts were included in this analysis. Verification that BRCA1/2mut testing was done on blood, saliva, and/or buccal samples was used to confirm that physicians were abstracting data from patients with gBRCA1/2muts as opposed to somatic BRCA1/2 mutations in the tumor. For US-based patients, the test type (somatic or germline) was confirmed by the laboratory where the testing was performed; data for laboratory confirmation of test type was not available for the 4 EU countries or Israel (Fig. 1).
The PRF included detailed questions on patient demographics, clinical assessments, clinical outcomes, adverse events experienced at the time of data collection among treated patients, treatment history, and physician-rated satisfaction with treatment. The treating physicians completed the data collection form using patient medical records as well as their clinical judgement and diagnostic skills consistent with their decision-making process during routine clinical practice. Each patient with a PRF was also invited to complete an optional written patient form independently of their physician immediately after consultation. The patient form contained questions on their education, employment status, input in treatment decisions, and current disease status. Patients were also asked to complete several PRO questionnaires that assessed their health-related QoL. PRO questionnaires were collected at 1 time point, the time of data collection, which corresponds to the treatment duration. Baseline PRO questionnaires were not collected.
Patients provided informed consent for use of their anonymized and aggregated data for research and in scientific publications. Data were aggregated and de-identified before receipt by Adelphi Real World. This research was approved by the Western Institutional Review Board (study protocol AG8643). Data collection was undertaken in line with European Pharmaceutical Marketing Research Association guidelines [11] and, as such, did not require ethics committee approval. This study was administered in full accordance with relevant legislation at the time of data collection, including the US Health Insurance Portability and Accountability Act of 1996 [12].
PRO assessments
Physicians invited patients to complete the following validated PRO questionnaires: the European Quality of Life 5-Dimensions 5-Levels (EQ-5D-5L), a widely used generic instrument that describes health-related QoL [13]; the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30), an integrated system for assessing health-related QoL in cancer patients [14, 15]; the EORTC breast cancer–specific module QLQ-BR23 [16]; and the Cancer Therapy Satisfaction Questionnaire (CTSQ) [17], which measures patient satisfaction with their current therapy.
The EQ-5D-5L comprises 5 dimensions, each being scored as numeric variables of 1 to 5 (1 = no problem; 5 = extreme problem) [13]. EQ-5D-5L summary index values derived from the EQ-5D-5L dimensions were also determined. The EQ-5D-5L was scored (Van Hout crosswalk method) based on standard individual 3-level value sets from the corresponding individual countries, except for Israel where the United Kingdom value sets were used [18]. The EQ-5D-5L includes a visual analog scale (VAS) that provides a quantitative measure of the patient’s perception of their overall current health, and for which the endpoints are “the best health you can imagine” and “the worst health you can imagine.”
The EORTC QLQ-C30 is composed of multi-item scales and single-item measures, including 5 functional scales, 3 symptom scales, a global health status (GHS)/QoL scale, and 6 single items [15]. Each multi-item scale includes a different set of items (ie, no item occurs in more than one scale). Items are scored on a 4-point scale from 1 (not at all) to 4 (very much), except for items contributing to the GHS/QoL, which are scored on a 7-point scale. All of the scales and single-item measures range in score from 0 to 100, with a high scale score representing a higher response level. The breast cancer module (QLQ-BR23) incorporates 5 multi-item scales that assess systemic therapy side effects, arm symptoms, breast symptoms, body image, and sexual functioning and single items to assess sexual enjoyment, hair loss, and future perspective [15]. The scoring for the QLQ-BR23 is the same in principle as that for the function and symptom scales/single items of the QLQ-C30.
The CTSQ contains 16 items and assesses 3 domains: Expectations of Therapy, Feelings About Side Effects, and Satisfaction With Therapy [17]. Items are scored on a scale of 1 to 5, with 1 representing the worst response and 5 the best response.
Physician satisfaction
Physicians were asked to describe their satisfaction with the current treatment for their patient’s ABC (very dissatisfied to very satisfied). The scores were dichotomized to a 0/1 variable (0 = very dissatisfied/dissatisfied/moderately satisfied; 1 = satisfied/very satisfied).
Statistical analysis
Descriptive summary statistics, including means, were calculated for continuous variables. Frequency counts and percentages were calculated for categorical variables. For any missing values, patients were removed from all analyses in which that variable was used. There was no imputation of missing data.
Patient demographics and baseline clinical characteristics were balanced using inverse-probability–weighted regression adjustment (IPWRA). The covariates balanced within the IPWRA were age at current treatment initiation, Charlson Comorbidity Index, baseline toxicities (constitutional, pulmonary, gastrointestinal, dermatologic, neurologic, psychological, physical, and pain), hormone receptor status, Eastern Cooperative Oncology Group (ECOG) performance status at current treatment initiation, stage at current treatment initiation, and number of treatments received in the advanced setting. Unadjusted demographics/clinical characteristics were analyzed using Student’s t tests and Fisher exact tests.
The IPWRA-adjusted CTSQ Patient Satisfaction, EQ-5D-5L Health Utility dimensions, EORTC QLQ-C30 and QLQ-BR23 scores, and physician satisfaction scores were compared between platinum/non–platinum-based chemotherapy (± immunotherapy) and PARPi monotherapy by logistic regression analysis. Mean scores ± standard error and 95% confidence intervals are presented. P values < 0.05 were considered significant. Analyses were performed using Stata v16.1 or later (StataCorp, College Station, TX, USA; 2019).