Real-World Patient-Reported Outcomes After Initiation of Adjuvant Ribociclib Plus Endocrine Therapy in Early HR+/HER2− Breast Cancer: A Multicentre Prospective Observational Study in Croatia (PRO-QoL-Cro)

Study type

• Study topic:
  Disease /health condition

  Other
• Study topic, other:
  Medical condition to be studied
• Study type:
  Non-interventional study
• Scope of the study:
  Evaluation of patient-reported outcomes

  Healthcare resource utilisation
• Data collection methods:
  Combined primary data collection and secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Medicinal product name:
  KISQALI
• Study drug International non-proprietary name (INN) or common name:
  RIBOCICLIB
• Anatomical Therapeutic Chemical (ATC) code:
  (L01EF02) ribociclib

  ribociclib
• Medical condition to be studied:
  Breast cancer
• Additional medical condition(s):
  Hormone receptor-positive, HER2-negative early breast cancer, AJCC 8th edition anatomic stage II to III

Population studied

• Short description of the study population:
  Adults aged 18 years or older, women and men, with histologically confirmed hormone receptor-positive, HER2-negative breast cancer of AJCC 8th edition anatomic stage II or III, who initiate adjuvant ribociclib in combination with endocrine therapy according to the Summary of Product Characteristics in routine clinical practice, and in whom adjuvant endocrine therapy was initiated within 12 months before baseline. Participants must be able to understand and complete the study questionnaires and must provide written informed consent.; ; Patients are not eligible if they have evidence of metastatic disease (AJCC stage IV) or locoregional or distant recurrence before baseline, prior treatment with a CDK4/6 inhibitor, an active second primary malignancy before initiation of ribociclib, contraindications to ribociclib or endocrine therapy according to the Summary of Product Characteristics, severe cognitive impairment, current participation in another interventional clinical trial, or are pregnant or breastfeeding.; ; Consecutive eligible patients are invited at three participating centres in Croatia until the planned sample size is reached.
• Age groups:
  • Adult and elderly population (≥18 years)

    • Adults (18 to < 65 years)

      • Adults (18 to < 46 years)
      • Adults (46 to < 65 years)
    • Elderly (≥ 65 years)

      • Adults (65 to < 75 years)
      • Adults (75 to < 85 years)
      • Adults (85 years and over)
• Estimated number of subjects:
  76

Study design details

• Study design:
  Multicentre, prospective, single-arm, non-interventional cohort study with primary data collection. Patient-reported outcomes are assessed at Months 0, 1, 3 and 6 after initiation of adjuvant ribociclib plus endocrine therapy.
• Main study objective:
  The primary objective is to estimate the within-patient change in health-related quality of life, as measured by the EQ-5D-5L utility index, from baseline (Month 0) to Month 6 after initiation of adjuvant ribociclib plus endocrine therapy in routine clinical practice.; ; Secondary objectives are: (1) to describe changes in EORTC QLQ-BR23 functioning and symptom domains over 6 months; (2) to evaluate changes in work productivity and activity impairment as measured by the WPAI:GH over 6 months; (3) to evaluate changes in informal care needs, operationalised as informal care hours per week, over 6 months; (4) to explore associations between treatment-related side effects and changes in patient-reported outcomes over time; (5) to explore associations between sociodemographic characteristics and patient-reported outcome trajectories over time; and (6) to explore whether the duration of prior endocrine therapy (up to 3 versus 4 to 12 months) is associated with patient-reported outcome trajectories during the 6 months.
• Setting:
  Three hospital oncology departments in Croatia: University Hospital Centre Split, University Hospital Centre Osijek and Clinical Hospital Dubrava. Consecutive eligible patients are identified and invited during routine outpatient visits within the enrolment period. Baseline is the day of initiation of adjuvant ribociclib in combination with endocrine therapy. Each participant is followed for six months, with assessments at Month 0, Month 1 (day 28 plus or minus 7 days), Month 3 (day 90 plus or minus 14 days) and Month 6 (day 180 plus or minus 21 days), calculated from baseline. Questionnaires are completed by participants on paper before the clinical consultation and, at baseline, before the first dose whenever feasible. Clinical data are abstracted from routine medical records, including selected data collected retrospectively for up to 12 months before baseline to characterise prior treatment and clinical context. There is no comparator arm and no randomisation. Treatment decisions, including dose modifications and discontinuation, are made solely by the treating physician according to clinical judgement and the Summary of Product Characteristics.
• Comparators:
  None. The study is single-arm. Each participant serves as her or his own reference, and the measure of interest is the within-patient change from baseline (Month 0) to Month 6. Exploratory subgroup contrasts are prespecified, including duration of endocrine therapy before baseline (up to 3 versus 4 to 12 months).
• Outcomes:
  Primary endpoint: within-patient change in the EQ-5D-5L utility index from baseline (Month 0) to Month 6.; ; Secondary endpoints, assessed at Months 0, 1, 3 and 6 and summarised as change from baseline to Month 6 and modelled as trajectories over time:; ; EORTC QLQ-BR23 functioning scales: body image, future perspective, sexual functioning;; EORTC QLQ-BR23 symptom scales: systemic therapy side effects, breast symptoms, arm symptoms, upset by hair loss;; WPAI:GH overall work impairment, absenteeism, presenteeism and activity impairment, with work-related domains analysed in participants employed at baseline and activity impairment in all participants;; informal care needs, measured as informal care hours per week, with caregiver type summarised descriptively.; ; Supportive descriptive outcomes: treatment interruptions, dose reductions and permanent discontinuation of ribociclib, adverse events, hospitalisations, sick leave and analgesic use.
• Data analysis plan:
  All outcomes are summarised descriptively at each assessment. The primary endpoint is analysed using a mixed model for repeated measures on the EQ-5D-5L utility index, with participant as a random effect and assessment time point as a fixed effect, adjusted for prespecified covariates including centre, age, anatomic stage and duration of endocrine therapy before baseline. Utility scoring uses the Hungarian value set in the primary analysis and the Italian value set in sensitivity analyses. EORTC QLQ-BR23 scales are scored according to the EORTC scoring manual. WPAI:GH domains are calculated using the standard scoring formulas. Informal care is analysed in two parts: the proportion of participants receiving any care, and hours per week among those receiving care; extreme values are checked against source responses and summarised using robust methods where appropriate. Changes are directionally harmonised across instruments. Missing data are assumed missing at random in the primary analysis, with sensitivity analyses under alternative assumptions and a descriptive account of reasons for missing assessments. Estimates are presented with 95 percent confidence intervals; no formal hypothesis testing is planned for the primary endpoint.