Abstract
Purpose:
Most studies of adherence to treatment for breast cancer have focused on early-stage patients. Findings from these studies may not generalize to patients with metastatic breast cancer (MBC). The objective of this study was to identify barriers and facilitators of adherence to cyclin-dependent kinase 4/6 (CDK4/6) inhibitors among patients with MBC, guided by the Social Ecologic Model (SEM).
Methods:
Patients with MBC (N=25), their caregivers (N=9), and oncology providers (N=13) completed semi-structured qualitative interviews exploring their experiences with CDK4/6 inhibitors. Interviews were audio recorded, transcribed verbatim, and analyzed by three raters using a combined deductive and inductive approach.
Results:
Qualitative analysis identified barriers and facilitators of adherence at each SEM level. Intrapersonal and interpersonal factors were most frequently discussed. Intrapersonal factors included knowledge/beliefs about CDK4/6 inhibitors, side effects, and establishing a routine. Interpersonal factors included effective communication with/coordination by the care team, support from family and friends, and information from other patients with MBC. Although less frequently discussed, policy factors (i.e., cost of CDK4/6 inhibitors) were of great concern to patients, caregivers, and providers.
Conclusion:
Barriers to adherence to CDK4/6 inhibitors exist at multiple levels. Our results underscore the potential value of a multilevel intervention (e.g., patient education, evidence-based strategies for symptom management, tips for open and assertive communication with providers, information about financial resources/support available, etc.) to support adherence in this population.
Keywords: breast cancer, metastatic breast cancer, CDK4/6 inhibitors, medication adherence, oral medication, Social Ecologic Model
Introduction
In the US, approximately 10% of breast cancer (BC) patients are diagnosed with de novo metastatic disease and 20–30% with localized BC will progress to metastatic breast cancer (MBC) [1–4]. MBC is not curable, but it is treatable [5]. Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors (palbociclib, ribociclib, abemaciclib), have become first-line therapy for hormone-receptor positive (HR+) MBC [6]. CDK4/6 inhibitors have nearly doubled progression-free survival for patients with HR+ MBC [7, 8] and increase overall survival in certain clinical subgroups [9, 10], even when accounting for dose delays and reductions [11]. However, several major side effects [8, 12–14], along with varying dosing schedules, frequent monitoring, and high out-of-pocket costs [12, 15–19], may present barriers to treatment initiation and adherence.
Most data on adherence to CDK4/6 inhibitors come from clinical trials, with a median relative dose intensity of 86–93% [7, 20–23]. Dose reduction rates ranged from 32–54% and rates of permanent discontinuation due to adverse events ranged from 3–20% [7, 20–24]. Outside of clinical trials, retrospective studies have reported CDK4/6 inhibitor dose reductions in 20–39% and discontinuation in 4–11% [25–31], suggesting the majority of MBC patients are adherent (albeit with dose reductions in a substantial minority). Identifying individuals at risk for poor adherence is critical, given non-adherence to other oral anticancer medications is associated with lower survival [32–34] and higher health care costs [35].
The limited research on predictors of adherence to oral anticancer agents for MBC suggests influences are multilevel. For example, patients receiving cancer care in urban settings and those from lower-income neighborhoods are less likely to receive CDK4/6 inhibitors for first-line treatment of MBC [36], suggesting patient- and clinic-level factors impact adherence. To our knowledge, no study has examined multilevel barriers to adherence in this context.
Therefore, guided by the Social Ecologic Model (SEM; Figure 1) [37, 38], we utilized qualitative interviews with MBC patients (n=25), their caregivers (n=9), and oncology providers (n=13; medical oncologists and oncology nurses). The SEM recognizes reciprocal relationships among intrapersonal (demographic, psychosocial), interpersonal (caregivers, providers), organizational (health care setting), community (home environment), and policy (health care coverage) influences on health. Thus, this study explored facilitators and barriers to adherence to CDK4/6 inhibitors at each level of the SEM.
Figure 1.
Conceptual model.
Methods
Setting
Interviews occurred at two NCI-designated sites with dedicated breast oncology clinics: (1) a Comprehensive Cancer Center in the southeastern US; and (2) a mid-Atlantic research consortium.
Procedures and Participants
All procedures were approved by the Institutional Review Boards at Moffitt Cancer Center (Advarra IRB #00000790) and Georgetown University (#2018–0485). Sample size was determined based on the principle of theoretical saturation, wherein interviews are conducted until no new information is obtained [39]. Based on our prior research [40–43] we anticipated 5–10 interviews would be required for saturation. Thus, our target sample size was 10 MBC patients, 10 caregivers, and 10 oncology providers.
Eligible patients were: (1) biological females; (2) age ≥18; (3) diagnosed with HR+ MBC; and (4) currently or previously treated with a CDK4/6 inhibitor for ≥1 month. Research staff reviewed clinic schedules, contacted potentially eligible patients via telephone, confirmed eligibility, and provided study information. Patients provided written informed consent by mail. Interviews were completed via phone (88%) or in-person (12%).
Eligible caregivers were: (1) age ≥18; and (2) identified by the patient as someone they do not pay for helping with their cancer care. Caregivers were referred by participating patients (i.e., “snowball sampling” [44]). Research staff contacted them via telephone, obtained written informed consent by mail, and conducted phone (89%) or in-person (11%) interviews.
All oncologists and nurses at each center providing MBC care were eligible; thus, providers were not identified by or linked with the patient or caregiver participants. Using institutional databases, research staff contacted providers via email, confirmed eligibility, obtained written informed consent, and conducted phone (69%) or in-person (31%) interviews.
Data Collection
A semi-structured interview guide based on the SEM was developed by three authors with expertise in qualitative methods (NP, SV, SO), and iteratively revised based on feedback from the study team [45]. During interviews, participants were asked to describe intrapersonal, interpersonal, organizational, community, and policy-level factors affecting adherence to CDK4/6 inhibitors (see Supplemental Materials). Interviewers (MM, NP, KL, SO) started with 7 predetermined questions and were permitted to probe interviewees’ responses through follow-up questions [46]. Interviews were audio-recorded and transcribed verbatim. Upon completion, participants self-reported sociodemographic characteristics. Participants received $20 for their time and effort.
Data Analysis
We utilized a combined deductive and inductive qualitative data analysis approach [47]. In anticipation that certain core concepts exist in the data, we developed a “start list” of expected themes [48–50], broadly representing levels of influence specified in the SEM. Then, three raters (MM, NP, SO) reviewed transcripts and developed a detailed codebook consisting of data-driven codes from the raw data [51]. Grounded theory was used to let themes emerge and the codebook was iteratively refined according to emergent themes. Codes represented specific sub-themes within the broad SEM domains (see Table 1).
Table 1.
Relationship between theory domains and data-driven themes and codes.
| SEM Domain | Themes | Codes |
|---|---|---|
| Intrapersonal | Patient adherence is high when they understand the treatment rationale and believe that the treatment is efficacious. |
|
| Taking CDK4/6 inhibitors was often framed as conditional on patients’ experiences of symptoms and side effects. |
|
|
| Patients started out using reminder tools, but for many, medications became a part of their daily routines. |
|
|
| Some patients are more or less likely to adhere to CDK4/6 inhibitors based on sociodemographic or personality characteristics. |
|
|
| Interpersonal | Effective communication with the care team and care coordination significantly reduce the burden of MBC and increase adherence to CDK4/6 inhibitors. |
|
| Family and friends often provide support for and motivation to take medication. |
|
|
| Other patients’ experiences are a valuable source of information. |
|
|
| “I am my own caregiver.” |
|
|
| Organizational | Available specialties and services can support adherence to CDK4/6 inhibitors. |
|
| Community | Patients and providers consider the safety and security of their communities in relation to medication adherence. |
|
| Policy | Cost of CDK4/6 inhibitors is a considerable barrier. |
|
We assessed intercoder reliability across repeated rounds of coding [52]. Transcripts were independently coded by two raters until satisfactory reliability (i.e., Cohen’s kappa ≥0.80) was achieved [53]. This occurred after 17 transcripts (36%) were independently coded. For independently coded transcripts, coding disagreements were resolved through discussion with a third rater until consensus was reached. The remaining 30 transcripts were coded by a single rater. Coding was conducted using MAXQDA v.12.
Results
Participant Demographics
See Table 2 for a full description of the sample. The participation rate was 68% for patients (25/37), 64% for caregivers (9/14), and 76% for providers (13/17). Patient participants were an average of 2.6 years (SD=1.7 years) post-MBC diagnosis and most (92%) were currently taking a CDK4/6 inhibitor. Two (8%) had discontinued a CDK4/6 inhibitor due to adverse events. Patients were taking or had previously taken palbociclib (96%) or abemaciclib (4%). All providers (100%) regularly prescribed or monitored patients on palbociclib; a subset also regularly prescribed/monitored ribociclib (62%) and/or abemaciclib (38%).
Table 2.
Participant sociodemographic and clinical characteristics.
| Total | Site 1 | Site 2 | |
|---|---|---|---|
| Patients with MBC | N=25 | n=18 | n=7 |
| Age (M, SD) | 60.7 (10.7) | 59.4 (10.6) | 64.0 (11.2) |
| Race (n, %) | |||
| White | 23 (92%) | 18 (100%) | 5 (71%) |
| Black | 1 (4%) | 0 (0%) | 1 (14%) |
| Other | 1 (4%) | 0 (0%) | 1 (14%) |
| Ethnicity: Hispanic/Latina (n, %) | 1 (4%) | 1 (6%) | 0 (0%) |
| Education (n, %) | |||
| High School/GED | 4 (16%) | 3 (17%) | 1 (14%) |
| Some college | 7 (28%) | 5 (28%) | 2 (29%) |
| ≥ College | 14 (56%) | 10 (56%) | 4 (57%) |
| Years since MBC diagnosis (M, SD) | 2.6 (1.7) | 2.6 (1.6) | 2.4 (1.9) |
| Currently taking CDK4/6 inhibitor (n, %) | 23 (92%) | 16 (89%) | 7 (100%) |
| CDK4/6 inhibitor(s) taken (n, %) | |||
| Palbociclib | 24 (96%) | 17 (94%) | 7 (100%) |
| Abemaciclib | 1 (4%) | 1 (6%) | 0 (0%) |
| Caregivers | N=9 | n=6 | n=3 |
| Age (M, SD) | 48.2 (16.9) | 49.7 (16.5) | 45.3 (21.2) |
| Gender (n, %) | |||
| Female | 2 (22%) | 1 (17%) | 1 (33%) |
| Male | 7 (78%) | 5 (83%) | 2 (67%) |
| Race (n, %) | |||
| White | 8 (89%) | 6 (100%) | 2 (67%) |
| Asian | 1 (11%) | 0 (0%) | 1 (33%) |
| Ethnicity: Hispanic/Latina (n, %) | 0 (0%) | 0 (0%) | 0 (0%) |
| Education (n, %)* | |||
| High school/GED | 1 (11%) | 1 (17%) | 0 (0%) |
| Some college | 1 (11%) | 1 (17%) | 0 (0%) |
| ≥ College | 6 (67%) | 4 (67%) | 2 (67%) |
| Relationship to patient (n, %) | |||
| Spouse | 7 (78%) | 5 (83%) | 2 (67%) |
| Child | 2 (22%) | 1 (17%) | 1 (33%) |
| Oncology Providers | N=13 | n=6 | n=7 |
| Age (M, SD) | 41.2 (8.8) | 42.2 (11.1) | 40.4 (7.1) |
| Gender (n, %) | |||
| Female | 11 (85%) | 5 (83%) | 6 (86%) |
| Male | 2 (15%) | 1 (17%) | 1 (14%) |
| Race (n, %) | |||
| White | 8 (62%) | 4 (67%) | 4 (57%) |
| Black | 1 (8%) | 0 (0%) | 1 (14%) |
| Asian | 2 (15%) | 1 (17%) | 1 (14%) |
| Other | 2 (15%) | 1 (17%) | 1 (14%) |
| Ethnicity: Hispanic/Latina (n, %) | 4 (31%) | 2 (33%) | 2 (29%) |
| Training background (n, %) | |||
| MD | 6 (46%) | 3 (50%) | 3 (43%) |
| RN | 7 (54%) | 3 (50%) | 4 (57%) |
| CDK4/6 inhibitor(s) prescribed/monitored† | |||
| Palbociclib | 13 (100%) | 6 (100%) | 7 (100%) |
| Ribociclib | 8 (62%) | 4 (67%) | 4 (57%) |
| Abemaciclib | 5 (38%) | 1 (17%) | 4 (57%) |
1 caregiver with missing data on education.
As participants could select more than one option, sums to >100%.
Themes
Qualitative analysis guided by the SEM identified several themes, including barriers and facilitators of adherence to CDK4/6 inhibitors. Tables 3–5 provide exemplar quotes from participants for each theme. As there were very few differences in themes between sites, we elected to merge sites in the reporting of results.
Table 3.
Representative quotes illustrating major themes at the intrapersonal level.
| Theme | Patients | Caregivers | Providers |
|---|---|---|---|
| Patient adherence is high when they understand the treatment rationale and believe that the treatment is efficacious. |
|
|
|
| Taking CDK4/6 inhibitors was often framed as conditional on patients’ experiences of symptoms and side effects. |
|
|
|
| Patients started out using reminder tools, but for many, medications became a part of their daily routines. |
|
|
|
| Some patients are more or less likely to adhere to CDK4/6 inhibitors based on sociodemographic or personality characteristics. |
|
|
|
Table 5.
Representative quotes illustrating major themes at the organizational, community, and policy levels.
| SEM Domain | Theme | Patients | Caregivers | Providers |
|---|---|---|---|---|
| Organizational | Available specialties and services can support adherence to CDK4/6 inhibitors. |
|
|
|
| Community | The safety and security of communities can affect medication adherence. |
|
|
|
| Policy | Cost of CDK4/6 inhibitors is a considerable barrier. |
|
|
|
Intrapersonal Factors
Theme 1: Patient adherence is high when they understand the treatment rationale and believe that the treatment is efficacious.
Participants emphasized that understanding the rationale for taking the medication is key for adherence (Table 3, Row 1, Patient #3/Provider #4). They also emphasized their belief that the medication was “working” (Table 3, Row 1, Patient #5/Patient #10). Although many patients were well-informed about MBC and their treatment, they expressed a desire for more educational materials (Table 3, Row 1, Patient #7). Providers and caregivers also noted the need to tailor information to patients’ needs (Table 3, Row 1, Caregiver #7/Provider #7).
Theme 2: Taking CDK4/6 inhibitors was often framed as conditional on patients’ experiences of symptoms and side effects.
While some patients reported limited side effects, others described experiencing fatigue, nausea, and diarrhea. Patients who described toxicities also mentioned dose reductions or interruptions as options for symptom management (Table 3, Row 2, Patient #3/Caregiver #23). Many patients described the side effects as an acceptable trade-off given the efficacy of the medication and/or in comparison to their prior experiences with chemotherapy (Table 3, Row 2, Patient #13). However, if side effects were to change or increase, they might reconsider taking CDK4/6 inhibitors (Table 3, Row 2, Patient #27).
Consistent with patients’ comments, providers reported few patients have difficulties with adherence due to the intolerability of side effects (Table 3, Row 2, Provider #1). Providers described working with patients to adjust dosing to address side effects. Providers also discussed expectations for side effects with their patients, saying patients will attribute physiological experiences to CDK4/6 inhibitors, even if it is likely not a medication side effect. Interestingly, some patients also discussed their difficulty in identifying and determining which side effects are important (Table 3, Row 2, Patient #12).
Theme 3: Patients started out using reminder tools, but for many, medications became a part of their daily routines.
Patients described using a variety of organizational and reminder tools to support adherence (calendars, phone reminders, pill box/organizer). Notably, those with a college degree were more likely to report use of these tools. However, patient use of these tools decreased as their medication routine became more established (Table 3, Row 3, Patient #5). Some patients also stated prior experience taking medications made it easy to adjust to taking CDK4/6 inhibitors (Table 3, Row 3, Patient #19).
Organizational tools were particularly important for patients with an alternating medication schedule. For example, one participant described using a pill box specifically for a 28-day medication cycle (Table 3, Row 3, Patient #6). Patients also mentioned receiving education from their care team regarding this dosing schedule (Table 3, Row 3, Patient #5).
Despite this alternating schedule, participants taking palbociclib reported little difficulty with adherence. This was corroborated by providers (Table 3, Row 3, Provider #1).
Theme 4: Some patients are more or less likely to adhere to CDK4/6 inhibitors based on sociodemographic or personality characteristics.
Although all groups discussed the role of sociodemographic and personality characteristics, they emphasized different traits as being important. Patients and caregivers highlighted personality characteristics – including organization, optimism, independence, resilience, persistence, adaptability to change, willingness to ask for help, and deference to authority – as key for adherence (Table 3, Row 4, Patient #3/Patient #12/Patient #14/Caregiver #3/Caregiver #23). Several patients also reflected that they were simply the type of person who takes their medication (Table 3, Row 4, Patient #4/Patient #7). In contrast, providers emphasized demographic characteristics as affecting adherence – including age, socioeconomic status, and education level (Table 3, Row 4, Provider Column).
Interpersonal Factors
Theme 5: Effective communication with the care team and care coordination significantly reduce the burden of MBC and increase adherence to CDK4/6 inhibitors.
Communication with the care team was consistently noted as a key facilitator of adherence. High-quality communication was described as reciprocal and relationship-building, resulting in trust and rapport between patients and providers (Table 4, Row 1, Patient #13/Caregiver #13/Provider #5).
Table 4.
Representative quotes illustrating major themes at the interpersonal level.
| Theme | Patients | Caregivers | Providers |
|---|---|---|---|
| Effective communication with the care team and care coordination significantly reduce the burden of MBC and increase adherence to CDK4/6 inhibitors. |
|
|
|
| Family and friends often provide support for and motivation to take medication. |
|
|
|
| Other patients’ experiences are a valuable source of information. |
|
|
|
| “I am my own caregiver.” |
|
N/A | N/A |
Patients, caregivers, and providers also discussed how effective care coordination (e.g., aligning appointments) could reduce the burden of frequent monitoring (Table 4, Row 1, Caregiver #23). Of note, care coordination is primarily the responsibility of oncology nurses and nurse navigators. One oncologist reflected on the importance of nursing staff for answering patients’ questions (Table 4, Row 1, Provider #4). Without these efforts, patients may face more barriers to care and oncologists would have an increased workload.
Theme 6: Family and friends often provide support for and motivation to take medication.
Although providers described having support from family as very important for adherence (Table 4, Row 2, Provider #5/Provider #7), patients were evenly divided on this issue. Some patients noted their family members remind them to take their medication (Table 4, Row 2, Patient #2), while others denied receiving such help. However, many patients reported they are motivated to take their medication to “be here with my family” (Table 4, Row 2, Patient #3). Thus, family and friends may provide motivation but not tangible support related to CDK4/6 inhibitors.
Theme 7: Other patients’ experiences are a valuable source of information.
Patients and caregivers described a variety of benefits from connecting online or in-person with other MBC patients (Table 4, Row 3, Patient #23/Caregiver #11). Interestingly, patients with a college degree discussed support groups and learning from other patients’ experiences less frequently. Providers acknowledged individual differences in support preferences and needs, and noted that not every patient will benefit from a support group (Table 4, Row 3, Provider #4).
Theme 8: “I am my own caregiver”.
A subset of patients strongly endorsed self-sufficiency regarding their medication adherence (Table 4, Row 4, Patient #10). These individuals stated they were able to take care of themselves, and they choose not to use available resources. This theme was not observed among caregivers or providers.
Organizational Factors
Theme 9: Available specialties and services can support adherence to CDK4/6 inhibitors.
Patients discussed many specialties that supported their care with social workers and pharmacists being noted most frequently (Table 5, Row 1, Patient #10/Patient #17). Social workers supported needs related to transportation, finances, and emotional support, while pharmacists provided education about CDK4/6 inhibitors and navigated insurance coverage.
Community Factors
Theme 10: The safety and security of communities can affect medication adherence.
This theme primarily emerged regarding patients who opt to have their CDK4/6 inhibitors mailed to their home. Patients and providers discussed the “trade-off” between convenience of home delivery and potential security issues (e.g., stolen packages) (Table 5, Row 2).
Policy Factors
Theme 11: Cost of CDK4/6 inhibitors is a considerable barrier.
All participants discussed the high cost of CDK4/6 inhibitors as a potential barrier to adherence (Table 5, Row 3, Patient #6/Patient #7/Caregiver #2). Although patients and caregivers did not report treatment delays due to cost, they did report that taking CDK4/6 inhibitors was contingent on financial assistance (Table 5, Row 3, Patient #2/Caregiver #3/Provider #2). Financial assistance programs were frequently available, but eligibility criteria often created a coverage gap for patients in need (Table 5, Row 3, Provider #5).
Patients and caregivers shared they often used their savings or lines of credit to pay for cancer care (Table 5, Row 3, Patient #10/Patient #18/Caregiver #13). Although cost itself did not lead to treatment delays, patients who were insured mentioned insurance approval wait time occasionally led to delays in medication refills.
Patients, caregivers, and providers all expressed concerns about Medicaid and Medicare coverage for CDK4/6 inhibitors. Patients expressed fear that changes in their insurance – specifically due to age or disability – would limit their ability to get CDK4/6 inhibitors, adding an additional source of stress (Table 5, Row 3, Patient #13).
Site 2 providers discussed clinical trials as one option for accessing CDK4/6 inhibitors, but this option was not mentioned by Site 1 providers; site differences were likely due to the clinical trials available at each institution. Providers expressed concerns that financial barriers would become more problematic after the clinical trials were completed (Table 5, Row 3, Provider #6).
Relative Frequency of SEM Factors
Intrapersonal and interpersonal factors were more frequently discussed than organizational, community, or policy factors (Figure 2).
Figure 2.
Relative frequency of Social Ecologic Model factors.
Discussion
The current study explored perspectives of MBC patients, their caregivers, and providers about use of CDK4/6 inhibitors. Although prior research has examined predictors of adherence to oral therapies among early stage BC patients [19, 54], this study is among the first to assess barriers and facilitators to oral anticancer medication adherence among MBC patients. Guided by the SEM, we identified multilevel factors impacting adherence. The resulting themes represent domains that are directly applicable to clinical practice, organizational structures, and healthcare policies.
Intrapersonal and interpersonal factors were the most frequently discussed domains and demonstrated the greatest variety in codes and subthemes. Consistent with the existing literature on adherence to oral anticancer therapies, important facilitators included knowledge and beliefs about the medication, patient-provider relationships, and concern about side effects [19]. Our findings also are consistent with the demonstrated importance of perceived benefits of the medication, as opposed to clinical markers of potential benefit, as more frequently predicting adherence [19]. However, social support –previously identified as a key component of medication adherence – was less crucial for patients in this study. About half of patients denied receiving social support in taking their medication. This is supported by the fact that we under-enrolled caregivers in this study. We had planned to recruit patient-caregiver dyads; however, most patients (16/25=64%) did not have an identifiable “caregiver”. It is possible that patients on endocrine therapy with CDK4/6 inhibitors do not need as much support as patients with more advanced, symptomatic disease. Thus, dyadic (i.e., patient- and caregiver-targeted) interventions in this setting may not be as beneficial as patient-targeted interventions.
Furthermore, MBC patients described a pattern of adjustment to the medication routine starting with using various organizational tools (e.g., calendars, phone reminders, pill box, etc.), but decreasing their use as the medication was incorporated into their daily routine. This is consistent with prior literature that demonstrates that the majority of patients are adherent to CDK4/6 inhibitors [7, 20–31]. However, certain groups, such as those with a poor understanding of the treatment, significant side effects, limited social support or access to supportive care services, and insufficient insurance coverage may be at risk for poor adherence. Behavioral interventions may be beneficial for the minority of MBC patients with adherence difficulties. For example, one study of adherence to capecitabine (an oral chemotherapy) among patients with cancer (38% BC) demonstrated that adherence support was associated with significant improvements in adherence among initially non-adherent patients [55]. Our data suggest adherence support may also be beneficial for MBC patients struggling with adherence to CDK4/6 inhibitors.
These themes demonstrate that adherence to CDK4/6 inhibitors is affected by multilevel factors. Thus, interventions to increase adherence will likely need to target multiple levels of influence and support care coordination. At the patient level, a wide variety of evidence-based behavior change techniques can be applied to the barriers identified here [56, 57]. Specifically, interventions incorporating techniques of shaping knowledge, problem solving/coping planning, prompts/cues, and social support may be particularly beneficial for addressing the identified barriers of knowledge, side effects, forgetting, and patient-provider communication. Patient-level interventions for improving adherence to CDK4/6 inhibitors among MBC patients might therefore include psychoeducation regarding medication and management of side effects, problem-solving for management of side effects, reminders to take medication, and skills-building for communicating with providers.
Organizational-level interventions might include policies and procedures that streamline care (i.e., interdisciplinary clinics, consecutive appointments), address logistic barriers (i.e., providing transportation or telehealth), and reduce medication costs (i.e., patient assistance programs). Data from this study indicate organizational and policy level barriers are often addressed by nurses, social workers, and pharmacists. Future interventions might incorporate these specialties; the nascent literature on adherence-promoting interventions for oral anti-cancer medications includes promising nurse- [58] and pharmacist-led interventions [59]. However, relying on these resources may be short-sighted. Both sites in this study were NCI-designated Comprehensive Cancer Centers; the availability of supportive care services (e.g., social work, specialty pharmacists) and/or care team structure (e.g., presence/number of oncology nurses, nurse navigators, nurse practitioners, physician assistants) may differ in other oncology practice settings. Future interventions should consider the financial and personnel restrictions of varied oncology practice settings.
Limitations
First, most patient participants were non-Hispanic White and highly educated. Although representative of patients at NCI-designated Comprehensive Cancer Centers [60], it is possible that theoretical saturation was only achieved due to the homogenous nature of the sample [61]. Furthermore, the lack of variability in participants’ demographic and clinical characteristics precluded stratified qualitative analyses. Additional research including heterogenous patient populations and care settings would increase the fidelity and utility of the findings presented here. Second, only 68% of patients approached agreed to participate. Because non-participants passively refused through non-response, we do not have data on reasons for refusal. Potential reasons may include: (1) patient death, (2) seasonality (some patients at Site #1 do not live in the area year-round and may not have received recruitment mailings), and (3) lack of time to participate due to active cancer treatment(s). Thus, results may be subject to selection bias. Third, at the time of interviewing (2018–2019), CDK4/6 inhibitors were relatively new. Thus, participants’ responses may be based on limited experience with these medications. Fourth, the institutions represented in this study are NCI-designated Comprehensive Cancer Centers; thus, results may not reflect community oncology practice settings. Given that receipt of CDK4/6 inhibitors varies by clinic site and patient neighborhood [36], future research needs to be conducted in community settings. Finally, this is a small, qualitative study. Future studies should quantitatively examine the SEM domains identified here in a large, representative sample of MBC patients. When integrated with the qualitative data presented here, results will inform specific multilevel intervention strategies.
Conclusions
By using a rigorous theoretical framework and synthesizing multidisciplinary perspectives, we identified targetable areas for increased adherence to CDK4/6 inhibitors. Based on our qualitative results, interventions that aim to increase adherence to CDK4/6 inhibitors should: educate patients regarding the treatment rationale; proactively address/minimize side effects; provide reminder tools (if necessary); encourage effective patient-provider communication; prompt patients to utilize social support; incorporate supportive specialties; and reduce medication costs. Future research is needed to develop and test multilevel interventions that incorporate these components to support medication adherence in this population.
Factors identified here might also enable researchers and clinicians to find and reach the minority of MBC patients who experience challenges with adherence to CDK4/6 inhibitors and would benefit most from the aforementioned interventions. Our results suggest that adherence is associated with treatment understanding, side effects, social support, and financial toxicity; screening these domains at CDK4/6 initiation and regular intervals thereafter may allow early identification and intervention to address issues related to CDK4/6 adherence. Improving adherence in this population may ultimately reduce healthcare costs and improve MBC outcomes.
Supplementary Material
Funding:
This work was supported by a Lombardi Survivorship Initiative Pilot Grant (PIs: O’Neill & Pensak) and grants from the National Cancer Institute (T32 CA090314, PIs: Brandon & Vadaparampil; P30 CA076292, PI: Cleveland; and P30 CA051008, PI: Weiner).
Footnotes
Conflicts of Interest: The authors have no conflicts of interest to disclose.
Ethics Approval: Study procedures adhered to the principles of the Declaration of Helsinki. All procedures were approved by the Institutional Review Boards at Moffitt Cancer Center (Advarra IRB #00000790, MCC #19466) and Georgetown University (#2018–0485).
Consent to Participate: Verbal or written informed consent was obtained from all individual participants included in the study.
Data Availability:
The datasets analyzed during the current study are not publicly available, as qualitative interview data cannot be completely anonymized, even when aliases are used to replace names. Data are available from the corresponding author on reasonable request.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The datasets analyzed during the current study are not publicly available, as qualitative interview data cannot be completely anonymized, even when aliases are used to replace names. Data are available from the corresponding author on reasonable request.