Aspects of Adjuvant CDK4/6 Inhibitors in Older Breast Cancer Patients - Focusing on Geriatric Screening

NCT ID: NCT07273357

Last Updated: 2025-12-09

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Total Enrollment: 200 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2026-04-01
• Study Completion Date: 2039-08-01

Brief Summary

Older breast cancer patients should not be categorically excluded from adjuvant therapies, including the recommended CDK4/6 inhibitors (CDK4/6i) administered in combination with endocrine therapy. Nevertheless, this population frequently presents with comorbidities that may increase susceptibility to treatment-related toxicities, including impacts on quality of life, which must be carefully considered when selecting therapeutic regimens. Given the limited representation of older patients in the clinical trials behind the recommendations for adjuvant CDK4/6i therapy, coupled with the uncertain magnitude of clinical benefit and the reported rates of toxicity and treatment discontinuation, it is essential to critically evaluate both efficacy and safety in this specific patient subgroup. National and international guidelines recommend the integration of geriatric assessments into routine clinical practice to facilitate individualized treatment decisions; however, such assessments are not yet widely implemented in many oncology departments and are not routinely in use to guide adjuvant CDK4/6i therapy.

This study aims to investigate the implementation of geriatric assessments in older breast cancer patients (≥70 years) and to examine multiple dimensions of CDK4/6i treatment in this cohort, including short- and medium-term effects on quality of life, dose intensity, and clinical outcomes. By doing so, the investigators seek to more accurately delineate the benefits and risks of adjuvant CDK4/6i therapy in this specific patient population.

Detailed Description

Adjuvant systemic therapy for breast cancer incorporates many different treatment modalities. CDK4/6 inhibitors (CDK4/6i) were initially approved in the metastatic setting, but now also as adjuvant treatment, concomitant with endocrine therapy for patients with estrogen-receptor positive/human epidermal growth factor receptor 2 -negative (ER+/HER2-) disease.

Only 15% of the study population in MonarchE was aged 65 and older, and the median age of 51 years is a decade younger than in the advanced setting pivotal studies. The median age in NATALEE was similarly 52 years, including only 773 out of 5,101 aged ≥65 years. Subgroup analysis from the MonarchE trial suggests benefit also in those >65 years old, but no statistically significant results exist so far. This might be attributed to a relatively small number of older participants, and the fact that these subgroup analyses were not pre-planned.

At present, specific guidelines regarding the use of adjuvant CDK4/6i in older patients are lacking. Given the importance of tailoring adjuvant treatment in this population, the implementation of geriatric screening in patients ≥70 years who are candidates for adjuvant CDK4/6i therapy is warranted. Furthermore, it is of clinical relevance to investigate the associations between geriatric screening assessment, quality of life, treatment-related toxicity, and discontinuation in this cohort. Outcomes such as hospitalization rates, recurrence, survival, and treatment dose intensity are also of particular interest in this patient population.

The hypothesis that the use of geriatric screening in routine clinical practice will reveal a relationship between frailty and decreased quality of life and higher risk of developing CDK4/6i toxicity. The investigators moreover anticipate a correlation between higher frailty and lower dose intensity, and poorer outcomes in terms of recurrence and survival.

The overall aim of this study is to examine different aspects of adjuvant CDK4/i in older early breast cancer patients. In more detail the aims are to investigate the association between geriatric frailty assessment (based on screening by the Geriatric 8 (G8) and Vulnerable Elders Survey-13 (VES-13) screening tools in older breast cancer patients that are to be treated with adjuvant CDK4/6i, and the risk of treatment side effects, discontinuation, patients reported quality of life, and hospitalization. Moreover, the investigators aim at exploring the correlation between frailty as assessed by geriatric screening and dose intensity and this impact on recurrence/survival. As exploratory analysis, different cut-offs for G8 and VES-13 score will be investigated in order to find stronger correlation between vulnerability/frailty and long-term outcomes in this patient cohort, and finally a comparison between the G8 and VES-13 performance.

In detail, the primary objectives are:

1. Association between frailty as assessed by G8 and VES-13 screening and CDK4/6i treatment side effects (adverse event (AE) grade ≥3)

2. Association between frailty as assessed by G8 and VES-13 screening and quality of life after initiating CDK4/6i, as reported by the patient

3. Association between frailty as assessed by G8 and VES-13 screening and hospitalization due to CDK4/6i

The secondary objectivs are:

4. Association between frailty as assessed by G8 and VES-13 screening and relative dose intensity (RDI, defined as the ratio of the drug dose administered in the actual time, over the planned dose in the planned time) by CDK4/6i and impact on breast cancer recurrence, overall and breast cancer-specific survival after 3, 5 and 10 years, respectively.

As exploratory analysis the following will be performed:

1. Explore whether different cut-offs of G8 and VES-13 score would result in a stronger correlation between vulnerability/frailty and long-term outcomes in this patient cohort. 2. Compare which geriatric screening tool that is more associated to outcomes

Conditions

Geriatric Assessment; Adjuvant Drug Therapy; Breast Cancer Early Stage Breast Cancer (Stage 1-3)

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Frail and fit older (≥70 years) breast cancer patients

Older (≥70 years) patients, with early stage breast cancer, initiating adjuvant CDK4/6 inhibitors that are defined as frail or fit according to G8 and VES-13

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• ≥70 years old
• Female/male
• Completed surgery (primary or after neoadjuvant therapy)
• Starting adjuvant CDK4/6i and endocrine therapy
• Cognitive performance to be able answer questionaries
• No language difficulties

Exclusion Criteria

• Impaired cognitive function not able to understand the study intention or perform questionaries
• Declining adjuvant CDK4/6i

• Minimum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Region Örebro County

OTHER

Sponsor Role: collaborator

Region Östergötland

OTHER

Sponsor Role: collaborator

Region Gävleborg

OTHER

Sponsor Role: collaborator

Västra Götalandsregionen

OTHER

Sponsor Role: collaborator

Linkoeping University

OTHER_GOV

Sponsor Role: collaborator

Örebro University, Sweden

OTHER

Sponsor Role: collaborator

Kalmar County Hospital

OTHER

Sponsor Role: collaborator

Region Jönköping County

OTHER_GOV

Sponsor Role: lead

Responsible Party

Christine Lundgren

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Christine Lundgren, MD

Role: STUDY_CHAIR

Department of Oncology, Jönköping, Region Jönköping County, Jönköping; Sweden,

Locations

Department of Oncology

Gävle, , Sweden

Department of Oncology

Gothenburg, , Sweden

Department of Oncology

Jönköping, , Sweden

Department of Oncology

Kalmar, , Sweden

Department of Oncology

Linköping, , Sweden

Department of Oncology

Örebro, , Sweden

Countries

Sweden

Central Contacts

Christine Lundgren, MD

Role: CONTACT

christine.lundgren@rjl.se

+46102422907

Facility Contacts

Ilke Cikman, MD

Role: primary

ilke.cikman@regiongavleborg.se

Karolina Larsson, MD

Role: primary

karolina.f.larsson@vgregion.se

Christine Lundgren, MD

Role: primary

christine.lundgren@rjl.se

+46102422907

Petra Hinnen, MD

Role: primary

petra.hinnen@regionkalmar.se

Jimmy Ekstrand, MD

Role: primary

jimmy.ekstrand@regionostergotland.se

Antonios Valachis, MD

Role: primary

antonios.valachis@oru.se

Other Identifiers

EPM 2025-06207-01

Identifier Type: -

Identifier Source: org_study_id