Recent systematic reviews and meta-analyses have reported positive benefit of multicomponent "bundled" palliative care interventions for patients and family caregivers while highlighting limitations in determining key elements and mechanisms of improvement. Traditional research approaches, such as the randomized controlled trial (RCT), typically treat interventions as "bundled" treatment packages, making it difficult to assess definitively which aspects of an intervention can be reduced or replaced or whether there are synergistic or antagonistic interactions between intervention components. Progressing toward palliative care interventions that are effective, efficient, and scalable will require new strategies and novel approaches. One such approach is the Multiphase Optimization Strategy (MOST), a framework informed by engineering principles, that uses a systematic process to empirically identify an intervention comprised of components that positively contribute to desired outcomes under real-life constraints. This article provides a brief overview and application of MOST and factorial trial design in palliative care research, including our insights from conducting a pilot factorial trial of an early palliative care intervention to enhance the decision support skills of advanced cancer family caregivers (Project CASCADE).

Introduction

Functional outcomes during non-small cell lung cancer (NSCLC) treatment are critically important to older adults. Yet, data on physical function and which measures best capture functional change remain limited.

Materials and methods

This multisite, mixed methods cohort study recruited adults ≥65 years with advanced NSCLC starting systemic treatment (i.e., chemotherapy, immunotherapy, and/or targeted therapy) with non-curative intent. Participants underwent serial geriatric assessments prior to starting treatment and at one, two, four, and six months, which included the Karnofsky Performance Scale (KPS, range: 0-100%), instrumental activities of daily living (IADL, range: 0-14), European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Physical Functioning subscale (EORTC QLQ-C30 PF, range: 0-100), and Life-Space Assessment (LSA, range: 0-120). For all measures, higher scores represent better functioning. In a qualitative substudy, 20 patients completed semi-structured interviews prior to starting treatment and at two and six months to explore how treatment affected their daily functioning. We created joint displays for each interview participant that integrated their longitudinal KPS, IADL, EORTC QLQ-C30 PF, and LSA scores with patient quotes describing their function.

Results

Among 87 patients, median age was 73 years (range 65-96). Mean pretreatment KPS score was 79% (standard deviation [SD] 13), EORTC QLQ-C30 PF was 69 (SD 23), and LSA was 67 (SD 28); median IADL was 13 (interquartile range [IQR] 10-14). At two months after treatment initiation, 70% of patients experienced functional decline on at least one measure, with only 13% of these patients recovering at six months. At two and six months, decline in LSA was the most common (48% and 35%, respectively). Joint displays revealed heterogeneity in how well each quantitative measure of physical function captured the qualitative patient experience.

Discussion

Functional decline during NSCLC treatment is common among older adults. LSA is a useful measure to detect subtle functional decline that may be missed by other measures. Given heterogeneity in how well each quantitative measure captures changes in physical function, there is value to including more than one functional measure in geriatric oncology research studies.

Background

Maintenance of function during cancer treatment is important to older adults. Characteristics associated with pretreatment life-space mobility and changes during non-small cell lung cancer (NSCLC) treatment remain unknown.

Methods

This mixed methods cohort study recruited adults age ≥65 with advanced NSCLC starting palliative chemotherapy, immunotherapy, and/or targeted therapy from a Comprehensive Cancer Center, Veterans Affairs, and safety-net clinic. Patients completed geriatric assessments including Life-Space Assessment (LSA) pretreatment and at 1, 2, 4, and 6 months after treatment initiation. LSA scores range from 0 to 120 (greater mobility); LSA <60 is considered restricted. We used mixed-effects models to examine pretreatment LSA, change from 0 to 1 month, and change from 1 to 6 months. A subgroup participated in semistructured interviews pretreatment and at 2 and 6 months to understand the patient experience of life-space change. For each interview participant, we created joint displays of longitudinal LSA scores juxtaposed with illustrative quotes.

Results

Among 93 patients, median age was 73 (range 65-94). Mean pretreatment LSA score was 67.1. On average, LSA declined 10.1 points from pretreatment to 1 month and remained stable at 6 months. Pretreatment LSA score was associated with several demographic, clinical, geriatric assessment, and symptom characteristics. LSA decline at 1 month was greater among patients with high anxiety (slope = -12.6 vs. -2.3, p = 0.048). Pretreatment body mass index <21 kg/m² was associated with LSA improvement from 1 to 6 months (slope = 4.1 vs. -0.04, p = 0.003). Joint displays illustrated the impact of different life-space trajectories on patients' lives in their words.

Conclusion

Older adults with NSCLC have low pretreatment life space with many developing restricted life space during treatment. Incorporating life-space assessments into clinical cancer care may help older adults concretely visualize how treatment might impact their daily function to allow for informed decision making and identify early changes in mobility to implement supportive interventions.

Context

Patients with advanced cancer often involve family caregivers in health-related decision-making from diagnosis to end-of-life; however, few interventions have been developed to enhance caregiver decision support skills.

Objectives

Assess the feasibility, acceptability, and potential efficacy of individual intervention components of CASCADE (CAre Supporters Coached to be Adept DEcision Partners), an early telehealth, palliative care coach-led decision support training intervention for caregivers.

Methods

Pilot factorial trial using the multiphase optimization strategy (October 2019-October 2020). Family caregivers and their care recipients with newly-diagnosed advanced cancer (n = 46 dyads) were randomized to1 of 8 experimental conditions that included a combination of one of the following three CASCADE components: 1) effective decision support psychoeducation; 2) decision support communication training; and 3) Ottawa Decision Guide training. Feasibility was assessed by completion of sessions and questionnaires (predefined as ≥80%). Acceptability was determined through postintervention interviews and participants' ratings of their likelihood to recommend. Measures of effective decision support and caregiver and patient distress were collected at Twelve and Twenty four weeks.

Results

Caregiver participants completed 78% of intervention sessions and 81% of questionnaires; patients completed 80% of questionnaires. Across conditions, average caregiver ratings for recommending the program to others was 9.9 on a scale from 1-Not at all likely to 10-Extremely likely. Individual CASCADE components were observed to have potential benefit for effective decision support and caregiver distress.

Conclusion

We successfully piloted a factorial trial design to examine components of a novel intervention to enhance the decision support skills of advanced cancer family caregivers. A fully-powered factorial trial is warranted.

Key message

We pilot tested components of CASCADE, an early palliative care decision support training intervention for family caregivers of patients with advanced cancer. CASCADE components were acceptable and the trial design feasible, providing promising future directions for palliative care intervention development and testing. Pilot results will inform a fully-powered trial.

Introduction

Palbociclib is a widely used treatment for advanced breast cancer in older adults. However, the existing evidence regarding its safety and tolerability in this age group is inconsistent and limited to retrospective subgroup or pooled analyses.

Materials and methods

We conducted a prospective single-arm multicenter phase 2 study to evaluate the safety and tolerability of palbociclib in participants aged 70 years or older with advanced hormone receptor-positive breast cancer. Participants were given palbociclib in combination with their physician's choice of endocrine therapy (letrozole or fulvestrant). The primary endpoint was the incidence of grade 3+ adverse events (AEs) by six months. Secondary endpoints included AE-related dose delays, dose reductions, early discontinuations, and hospitalizations. Additionally, we compared these endpoints by age groups (70-74 and ≥ 75 years).

Results

Of the 90 participants (median age 74 years [70-87]) enrolled, 75.6% (95% confidence interval [CI], 65.4-84.0) had grade 3+ AEs by six months. The most frequent grade 3+ AEs were neutropenia (61%), fatigue (4%), and nausea (3%). Febrile neutropenia was uncommon (1.1%). Due to AEs, 36% had dose delays, 34% had dose reductions, 10% had early discontinuations, and 10% had hospitalizations. Compared to those aged 70-74 years, participants aged ≥75 years had higher rates of early discontinuations (5.9% vs 15.9%, a difference of 9.5% [95% CI 3.5%-22.5%]).

Discussion

Palbociclib has an overall favorable safety profile in adults aged ≥70 with advanced breast cancer. However, adults ≥75 years had a trend toward higher rates of AE-related early discontinuations compared to those 70-74 years. Further research is needed to evaluate tolerability and improve the delivery of palbociclib in older adults.

Clinicaltrials

gov:NCT03633331.