Research Advocacy Network

PurposeAdding CDK4/6 inhibitors (CDK4/6is) to endocrine therapy (ET) for HR+/HER2− early breast cancer (EBC) demonstrated statistically significant invasive disease-free survival (iDFS) benefits in monarchE (node positive, high risk, stage II/III) and NATALEE (select N0 and all macroscopic N1, stage II/III). This study evaluated patient preferences for EBC treatment attributes and how these may translate for CDK4/6i selection.MethodsA web-based discrete choice experiment survey was conducted among US-based adult women with self-reported stage II/III HR+/HER2− EBC. Eight attributes were included, informed by 14 qualitative interviews (to identify most relevant attributes), expert clinical input, and differentiating features between CDK4/6is: efficacy (5-year iDFS), adverse events (venous thromboembolic event [VTE], diarrhea, fatigue), number of blood tests, number of electrocardiograms (EKGs), treatment duration, and schedule. Participants selected scenarios that best reflected their preferences from 10 choice cards, each displaying a pair of hypothetical treatment profiles. A conditional logit regression model was used to estimate preference weights and relative importance (RI) of attributes.ResultsA total of 409 women participated. Patient preferences, from high to low RI, were higher efficacy, lower diarrhea risk, lower fatigue risk, shorter treatment duration, and lower VTE risk. Number of blood tests, number of EKGs, and treatment schedule were less important. Utility scores were higher for reconstructed treatment profiles that resembled ribociclib.ConclusionThis study demonstrated that patients prefer adjuvant treatment with higher efficacy and lower risk of adverse events. These data will aid shared decision-making when discussing the addition of CDK4/6is to adjuvant ET for eligible patients with HR+/HER2− EBC.

Breast cancer is treated with a multidisciplinary approach involving surgical oncology, radiation oncology, and medical oncology. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer include recommendations for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget's disease, Phyllodes tumor, inflammatory breast cancer, and management of breast cancer during pregnancy. The content featured in this issue focuses on the recommendations for overall management of systemic therapy (preoperative and adjuvant) options for nonmetastatic breast cancer. For the full version of the NCCN Guidelines for Breast Cancer, visit NCCN.org.

As outcomes improve in early-stage breast cancer, clinical trials are undergoing a paradigm shift from intensification trials (more therapy) to improve survival to optimization trials, which assess the potential for using less toxic therapy while preserving survival outcomes. However, little is known about physician perspectives in community and academic settings about possible barriers and facilitators that could affect accrual to optimization clinical trials and the generalizability of future findings. We conducted a qualitative study with semistructured interviews of medical oncologists from different academic and community practices to assess their perspectives on optimization trials. Interviews were audio-recorded and transcribed. Three independent coders used a content analysis approach to analyze transcripts using NVivo. Major themes and exemplary quotes were extracted. All 39 physicians reported that they would enroll patients in optimization clinical trials. Oncologists highlighted specific reasons to consider optimization trials. These included quality-of-life improvement by reducing toxicity, reduction in financial toxicity, fertility preservation, ability to avoid chemotherapy, minimization of overtreatment in patients with comorbid conditions, personalized treatment, opportunities to test novel therapies, and leveraging the availability of targeted therapies. Oncologists also identified accrual barriers, such as tumor-specific biology, individual (host) factors, prognostic markers of risk, access to therapies, provider experience, and system constraints. They voiced recommendations regarding preliminary data, trial design, and tools to support enrollment in optimization trials. Although oncologists are generally willing to enroll patients on optimization clinical trials, barriers affect their acceptance. A scientific focus on overcoming these barriers is needed to support future enrollment on trials tailoring therapy on the basis of risk and potential benefit to allow true personalization of treatment.

The therapeutic options for patients with noninvasive or invasive breast cancer are complex and varied. These NCCN Clinical Practice Guidelines for Breast Cancer include recommendations for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget disease, phyllodes tumor, inflammatory breast cancer, and management of breast cancer during pregnancy. The content featured in this issue focuses on the recommendations for overall management of ductal carcinoma in situ and the workup and locoregional management of early stage invasive breast cancer. For the full version of the NCCN Guidelines for Breast Cancer, visit NCCN.org.

Patient-reported outcome measures (PROMs) that assess how patients feel and function have potential for evaluating quality of care. Stakeholder recommendations for PRO-based performance measures (PMs) were elicited, and feasibility testing was conducted at six cancer centers. Interviews were conducted with 124 stakeholders to determine priority symptoms and risk adjustment variables for PRO-PMs and perceived acceptability. Stakeholders included patients and advocates, caregivers, clinicians, administrators, and thought leaders. Feasibility testing was conducted in six cancer centers. Patients completed PROMs at home 5-15 days into a chemotherapy cycle. Feasibility was operationalized as ≥ 75% completed PROMs and ≥ 75% patient acceptability. Stakeholder priority PRO-PMs for systemic therapy were GI symptoms (diarrhea, constipation, nausea, vomiting), depression/anxiety, pain, insomnia, fatigue, dyspnea, physical function, and neuropathy. Recommended risk adjusters included demographics, insurance type, cancer type, comorbidities, emetic risk, and difficulty paying bills. In feasibility testing, 653 patients enrolled (approximately 110 per site), and 607 (93%) completed PROMs, which indicated high feasibility for home collection. The majority of patients (470 of 607; 77%) completed PROMs without a reminder call, and 137 (23%) of 607 completed them after a reminder call. Most patients (72%) completed PROMs through web, 17% paper, or 2% interactive voice response (automated call that verbally asked patient questions). For acceptability, > 95% of patients found PROM items to be easy to understand and complete. Clinicians, patients, and other stakeholders agree that PMs that are based on how patients feel and function would be an important addition to quality measurement. This study also shows that PRO-PMs can be feasibly captured at home during systemic therapy and are acceptable to patients. PRO-PMs may add value to the portfolio of PMs as oncology transitions from fee-for-service payment models to performance-based care that emphasizes outcome measures.

A panel discussion on controversies in breast cancer screening held recently at the NCCN 21st Annual Conference included only a few controversies. Representatives of the U.S. Preventive Services Task Force, American Cancer Society, and NCCN disagreed primarily on 2 main areas: when to start screening (ages 40, 45, or 50 years) and frequency of screening (annual vs biennial). Panelists from these organizations presented the rationales for their respective recommendations.

These NCCN Guidelines Insights highlight the important updates specific to the management of HER2-positive metastatic breast cancer in the 2013 version of the NCCN Clinical Practice Guidelines in Oncology for Breast Cancer. These include new first-line and subsequent therapy options for patients with HER2-positive metastatic breast cancer.

Abstract Background: Most patients with metastatic breast cancer are treated with chemotherapies and/or targeted therapies. These therapies have toxicity profiles that vary with agent(s) used. Patient attitudes towards different adverse events (AE's) may vary and factor into treatment decisions. Different patients may have specific feelings about tolerable and unacceptable AE's, especially when balanced against possible treatment benefit. As more agents/combinations become available, it becomes increasingly important to understand which adverse events impact treatment decisions. Previous research has shown that conjoint analysis (CA) is a valid methodology that allows patients to express preferences and is particularly useful when designed based on specific treatment profiles (Smith, ASCO 2011; Smith, ASCO 2012). Methods: The objective of this study was to assess patient preferences using CA based on profiles of two MBC regimens (trastuzumab+docetaxel and T-DM1). Patients were presented pairs of hypothetical treatments (describing benefit, AE's, and cost) and asked what their preferred alternative was; a follow-up question asked if they would take the treatment if it were the only option available. Five AE's (alopecia, peripheral neuropathy, diarrhea, fatigue, and neutropenia) with differing likelihood, severity, and/or duration were included. There were 3 stages in preparing the CA survey: the first comprised two online focus groups conducted with patients with metastatic disease. Stage 2 included the development of the CA survey using patient language to describe the AE's and their impact, as well as images to represent likelihoods, progression-free survival (PFS), and costs. Stage 3 is initiating and will recruit patients with the assistance of several breast cancer organizations (target n= 600). Analysis of response patterns allows study of the influence of each variable and provides a basis for prediction of treatment choice for any combination of benefit, AE's, and cost. Final analysis will be complete in September 2012. Results: Findings from the focus groups facilitated an understanding of PFS, of experience with and impact of the AE's on decision-making, and of attitudes. In Stage 2, the survey was pretested with seven patients and took approximately 20 minutes to complete. Feedback suggested the questions were relevant and realistic. Suggestions allowed for improvement of the CA explanatory material, as well as refinement of a few answer choices to questions outside the CA section of the survey. Final study results will present the proportion of patients who are predicted to prefer each of two treatment profiles, the impact of each attribute level on treatment preference and differing preferences seen in patient subgroups. This information will provide valuable insight into patient preferences and inform future development of new therapies. In addition, these results may generate discussion and consideration of patient preferences in conversations about patient care and treatment selection. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-09-11.

Abstract BACKGROUND:Population‐based studies have shown improved survival for patients diagnosed with metastatic breast cancer over time, presumably because of the availability of new and more effective therapies. The objective of the current study was to determine whether survival improved for patients who developed distant recurrence of breast cancer after receiving adjuvant therapy.METHODS:Adjuvant chemotherapy trials coordinated by the Eastern Cooperative Oncology Group that accrued patients between 1978 and 2002 were reviewed. Survival after distant disease recurrence was estimated for progressive time periods, and adjusted for baseline covariates in a Cox proportional hazards model.RESULTS:Of the 13,785 patients who received adjuvant chemotherapy in 11 trials, 3447 (25%) developed distant disease recurrence; the median survival after recurrence was 20 months (95% confidence interval, 19 months‐21 months). Factors associated with inferior survival included a shorter distant recurrence‐free interval (DRFI), estrogen receptor‐negative and progesterone receptor‐negative disease, the number of positive axillary lymph nodes present at the time of diagnosis, and black race (P < .0001 for all). When the time period of recurrence was added to the model, it was not found to be significantly associated with survival for the general population with disease recurrence. Survival improved over time only in those patients with hormone receptor‐negative disease with a DRFI ≤ 3 years, both among the 5 most recent and the entire trial data sets (P = .01 and P = .05, respectively).CONCLUSIONS:In contrast to reports from population‐based studies, no general improvement in survival was observed over the last 30 years for patients who developed distant disease recurrence after adjuvant chemotherapy after adjusting for DRFI. Improved survival for patients with hormone receptor‐negative disease with a short DRFI suggests a benefit from trastuzumab. Cancer 2013. © 2012 American Cancer Society.