Living with metastatic breast cancer (LIMBER): experiences, quality of life, gaps in information, care and support of patients in the UK.

PURPOSE: To determine the experiences, information, support needs and quality of life of women in the UK living with metastatic breast cancer (MBC) to provide content for educational materials. METHODS: An online survey, hosted for 3 months on a UK MBC charity website, comprised sections covering issues such as communication about MBC treatment and management, helpful and less helpful things that healthcare professionals, family and friends did or said and completion of the Patient Roles and Responsibilities Scale (PRRS). RESULTS: A total of 143 patients participated; 48/143(33%) presented de novo; 54/143(38%) had been living with MBC > 2 years. PRRS analysis revealed that MBC imposed a serious impact upon most respondents' own caring abilities and social lives. A majority 98/139 (71%) wished they had known more about MBC before their diagnosis; 63/134(47%) indicated that they still did not fully understand their illness; merely 78/139(56%) had access to a specialist nurse and only 69/135(51%) had been offered any additional support. Respondents reported little consideration given to their lifestyle/culture during consultations and inconsistent information, support services, continuity of care or access to clinical trials. They commented upon things health care professionals/friends and family did or said that were useful and cited other behaviours that were especially unhelpful. CONCLUSIONS: MBC exerted a deleterious impact upon patients' activities of daily living which were exacerbated in part by significant gaps in support, communication and information. IMPLICATIONS FOR CANCER SURVIVORS: LIMBER results are informing the content of educational materials currently being developed for patients' formal and informal carers.

IMPARTER, Phase 1 of an intervention to improve patients' understanding of gene expression profiling tests in breast cancer.

PURPOSE: To compare participants' knowledge about gene expression profiling (GEP) tests and recurrence risks after reading an information leaflet with that following viewing of an information film. METHODS: Using a randomised cross-over design, at time-point one (T1), women aged 45-75 years without breast cancer either read leaflets or watched information films about Oncotype DX or Prosigna tests. Participants answered nine questions assessing knowledge (maximum score 18). Next-day information in the opposite modality was provided and knowledge re-assessed. Additional questions probed which format was easiest to understand, participants' preferences for film or leaflet and their reasons for these. RESULTS: 120 women participated (60 received OncotypeDX films and leaflets; 60 received the Prosigna versions). T1 mean knowledge scores were higher following film viewing (13.37) compared with that after reading leaflets (9.25) (mean difference 4.1; p < 0.0001; 95% CI 3.2, 5.0). When participants read leaflets first and subsequently viewed films, all increased their scores (mean + 6.08, from T1 of 9.25, p < 0.0001; 95% CI 5.44, 6.72). When films were viewed first, followed by leaflets, (36/60, 60%), participants' scores declined (mean-1.55 from T1 of 13.37, p < 0.001; 95% CI -2.32, -0.78). A majority of participants expressed preferences for the films (88/120, 73.3%) irrespective as to whether they described OncotypeDX or Prosigna. Reasons included the clarity, ease of understanding, visual material and reassuring voice-over. CONCLUSION: Discussions between oncologists and patients about recurrence risk results can be challenging. Information leaflets may aid understanding but often employ complex language. Information films significantly improved knowledge and were preferred by participants.

A structured review of quality of life in advanced and high-risk cutaneous squamous cell carcinoma shows the need for more studies and better measures.

Background: Cutaneous squamous cell carcinoma (cSCC) accounts for nearly a quarter of non-melanoma skin cancers. Studies reporting Quality of Life (QoL) in this group focus on early stage disease. A small proportion of cSCC patients have high-risk or advanced disease, with potentially significant QoL impacts, yet are largely overlooked. Aims: This structured review appraises measures and published QoL outcomes in this group. Materials & Methods: We conducted searches in MEDLINE, EMBASE, CINAHLplus and PsycInfo in June 2020 (updated in October) to identify publications specifically reporting QoL outcomes in this cohort. Returns were reviewed against a strict set of eligibility criteria. Results: We identified seven publications for inclusion; three relating to high-risk cSCC, three to metastatic disease and one to unresectable disease. Publications were appraised for quality using the Mixed Methods Appraisal Tool. Only one fulfilled more than two of the five quality criteria. Studies employed a range of patient reported outcome measures to assess QoL, both generic and disease specific. Discussion: All studies with multiple time-points reported stable or improving QoL, however extrapolation of these findings to the cSCC population is not warranted due to study limitations including mixed populations, incomplete data sets or single measurements. We set out to review the QoL literature for high-risk and advanced cSCC and found a small and disparate body of evidence. Studies varied significantly in terms of study population, design and quality. While the identified studies suggested stable or improving QoL, we question the choice of measures used and highlight the need for further work in this area. Conclusion: While there are some published reports about quality of life for patients with early stage cutaneous squamous cell carcinoma, these impacts for the high-risk or advanced cohort are largely unexplored. We conducted a structured review of published measures and outcomes used in this cohort and found a demonstrable need for further, targeted, exploration of patient needs in this area.

Digital health for optimal supportive care in oncology: benefits, limits, and future perspectives.

BACKGROUND: Digital health provides solutions that capture patient-reported outcomes (PROs) and allows symptom monitoring and patient management. Digital therapeutics is the provision to patients of evidence-based therapeutic interventions through software applications aimed at prevention, monitoring, management, and treatment of symptoms and diseases or for treatment optimization. The digital health solutions collecting PROs address many unmet needs, including access to care and reassurance, increase in adherence and treatment efficacy, and decrease in hospitalizations. With current developments in oncology including increased availability of oral drugs and reduced availability of healthcare professionals, these solutions offer an innovative approach to optimize healthcare resource utilization. DESIGN: This scoping review clarifies the role and impact of the digital health solutions in oncology supportive care, with a view of the current segmentation according to their technical features (connection to sensors, PRO collection, remote monitoring, self-management in real time…), and identifies evidence from clinical studies published about their benefits and limitations and drivers and barriers to adoption. A qualitative summary is presented. RESULTS: Sixty-six studies were identified and included in the qualitative synthesis. Studies supported the use of 38 digital health solutions collecting ePROs and allowing remote monitoring, with benefits to patients regarding symptom reporting and management, reduction in symptom distress, decrease in unplanned hospitalizations and related costs and improved quality of life and survival. Among those 38 solutions 21 provided patient self-management with impactful symptom support, improvement of QoL, usefulness and reassurance. Principal challenges are in developing and implementing digital solutions to suit most patients, while ensuring patient compliance and adaptability for use in different healthcare systems and living environments. CONCLUSIONS: There is growing evidence that digital health collecting ePROs provide benefits to patients related to clinical and health economic endpoints. These digital solutions can be integrated into routine supportive care in oncology practice to provide improved patient-centered care.

Talking about risk in the context of genomic tests (TARGET): development and evaluation of an educational program for clinicians.

PURPOSE: Gene expression profiling (GEP) test scores calculate risks of recurrence and likely benefit of adjuvant chemotherapy in ER-positive, HER2-negative, early-stage breast cancer. As health literacy and numeracy skills in the general population are poor, healthcare professionals (HCPs) require a wide repertoire of communication skills to explain clearly risk of recurrence scores (RSs) and uncertainty. We developed and evaluated an educational program for HCPs discussing GEP test results and adjuvant treatment. METHODS: Eight-hour workshops contained elements aimed at improving knowledge, communication skills and self-awareness; these included the science underpinning GEP tests, an interactive risk psychology lecture, exercises and facilitated group discussions regarding seven filmed scenarios involving discussions about high, intermediate and low RSs. Attendees were recorded explaining RSs with patient simulators pre and post workshop. Researchers, blinded to time point, analysed recordings using a study-specific scoring system. Primary objective outcomes were improvements post workshop in HCPs' competence and confidence when communicating 17 pre-specified key information areas. We estimated odds ratios (OR) using conditional logistic regression to compare pre- and post-workshop scores. RESULTS: 65 HCPs attended. Objective analyses revealed significant positive shifts post workshop which included explaining GEP tests (OR 2.98; 95% CI 1.38-6.42; P = .001), recurrence RSs (OR 3.99; 95% CI 1.72-9.25; P < .001), benefits of chemotherapy (OR 3.99; 95% CI 1.82-8.75; P < .001; and harms OR 2.31; 95% CI 1.37-3.92; P < .001) using jargon free language (OR 5.29; 95% CI 2.27-12.35; P < .001). Patient simulator assessments also showed significant improvements as did HCPs' self-assessments and ratings of their self-confidence when discussing different GEP tests with diverse patient types (P < .001). CONCLUSION: These short, intensive, interactive TARGET workshops significantly improved HCPs' communication about GEP results in ways likely to promote more informed decision-making by patients about chemotherapy.

Effects of neratinib on health-related quality of life in women with HER2-positive early-stage breast cancer: longitudinal analyses from the randomized phase III ExteNET trial.

BACKGROUND: We report longitudinal health-related quality-of-life (HRQoL) data from the international, randomized, double-blind, placebo-controlled phase III ExteNET study, which demonstrated an invasive disease-free survival benefit of extended adjuvant therapy with neratinib over placebo in human epidermal growth factor receptor-2-positive early-stage breast cancer. PATIENTS AND METHODS: Women (N = 2840) with early-stage HER2-positive breast cancer who had completed trastuzumab-based adjuvant therapy were randomly assigned to neratinib 240 mg/day or placebo for 12 months. HRQoL was an exploratory end point. Patients completed the Functional Assessment of Cancer Therapy-Breast (FACT-B) and EuroQol 5-Dimensions (EQ-5D) questionnaires at baseline and months 1, 3, 6, 9, and 12. Changes from baseline were compared using analysis of covariance with no imputation for missing values. Sensitivity analyses used alternative methods. Changes in HRQoL scores were regarded as clinically meaningful if they exceeded previously reported important differences (IDs). RESULTS: Of the 2840 patients (intention-to-treat population), 2407 patients were evaluable for FACT-B (neratinib, N = 1171; placebo, N = 1236) and 2427 patients for EQ-5D (neratinib, N = 1186; placebo, N = 1241). Questionnaire completion rates exceeded 85%. Neratinib was associated with a decrease in global HRQoL scores at month 1 compared with placebo (adjusted mean differences: FACT-B total, -2.9 points; EQ-5D index, -0.02), after which between-group differences diminished at later time-points. Except for the FACT-B physical well-being (PWB) subscale at month 1; all between-group differences were less than reported IDs. The FACT-B breast cancer-specific subscale showed small improvements with neratinib at months 3-9, but all were less than IDs. Sensitivity analyses exploring missing data did not change the results. CONCLUSIONS: Extended adjuvant neratinib was associated with a transient, reversible decrease in HRQoL during the first month of treatment, possibly linked to treatment-related diarrhea. With the exception of the PWB subscale at month 1, all neratinib-related HRQoL changes did not reach clinically meaningful thresholds. ClinicalTrials.gov: NCT00878709.

Treatment Experiences, Information Needs, Pain and Quality of Life in Men with Metastatic Castrate-resistant Prostate Cancer: Results from the EXTREQOL Study.

AIMS: Delaying progression, ameliorating symptoms and maintaining quality of life (QoL) are primary aims of treatment for metastatic castrate-resistant prostate cancer (mCRPC). Real-world rather than clinical trial data about symptoms and side-effects are sparse. In EXTREQOL, patients' QoL, pain and information needs were recorded during treatment. MATERIAL AND METHODS: Men with mCRPC from 20 UK cancer centres starting various systemic mCRPC treatments completed QoL, pain and information needs questionnaires at baseline, 3 and 6 months. RESULTS: In total, 132 patients were recruited. Overall QoL declined significantly by 6 months (Functional Assessment of Cancer Therapy-Prostate [FACT-P] mean = -3.89, 95% confidence interval -6.7 to -1.05, P = 0.007; Trial Outcome Index [TOI] analysis mean = -3.10, 95% confidence interval -5.34 to -0.83, P = 0.007). Those who came off novel therapy and remained on luteinising hormone-releasing hormone agonist therapy alone had worse scores than patients receiving concomitant chemotherapy (Prostate Concerns Subscale mean difference = -4.45, 95% confidence interval -7.06 to -1.83, P = 0.001; TOI mean difference = -5.62, 95% confidence interval -10.97 to -0.26, P = 0.040). At 3 and 6 months, men who reported pain at baseline improved (43%, 40%), but for others pain levels remained the same (45%, 42%) or worsened (13%, 18%). Information regarding supportive care was lacking throughout the period of time on the study. CONCLUSION: Most mCRPC treated patients experience reduced QoL and inadequate pain control. More help with pain management and better information provision regarding supportive care is warranted.

Do drugs offering only PFS maintain quality of life sufficiently from a patient's perspective? Results from AVALPROFS (Assessing the 'VALue' to patients of PROgression Free Survival) study.

PURPOSE: Trials of novel drugs used in advanced disease often show only progression-free survival or modest overall survival benefits. Hypothetical studies suggest that stabilisation of metastatic disease and/or symptom burden are worth treatment-related side effects. We examined this premise contemporaneously using qualitative and quantitative methods. METHODS: Patients with metastatic cancers expected to live > 6 months and prescribed drugs aimed at cancer control were interviewed: at baseline, at 6 weeks, at progression, and if treatment was stopped for toxicity. They also completed Functional Assessment of Cancer Therapy (FACT-G) plus Anti-Angiogenesis (AA) subscale questionnaires at baseline then monthly for 6 months. RESULTS: Ninety out of 120 (75%) eligible patients participated: 41 (45%) remained on study for 6 months, 36 progressed or died, 4 had treatment breaks, and 9 withdrew due to toxicity. By 6 weeks, 66/69 (96%) patients were experiencing side effects which impacted their activities. Low QoL scores at baseline did not predict a higher risk of death or dropout. At 6-week interviews, as the side effect severity increased, patients were significantly less inclined to view the benefit of cancer control as worthwhile (X2 = 50.7, P < 0.001). Emotional well-being initially improved from baseline by 10 weeks, then gradually returned to baseline levels. CONCLUSION: Maintaining QoL is vital to most patients with advanced cancer so minimising treatment-related side effects is essential. As side effect severity increased, drugs that controlled cancer for short periods were not viewed as worthwhile. Patients need to have the therapeutic aims of further anti-cancer treatment explained honestly and sensitively.

Efficacy and safety of subcutaneous trastuzumab and intravenous trastuzumab as part of adjuvant therapy for HER2-positive early breast cancer: Final analysis of the randomised, two-cohort PrefHer study.

AIM: To assess efficacy (event-free survival, EFS) and safety in patients followed up for 3 years in the PrefHer study (NCT01401166). PATIENTS AND METHODS: Post surgery and post chemotherapy in the (neo)adjuvant setting, patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer were randomised to receive four cycles of the subcutaneous form of trastuzumab (Herceptin® SC [H SC] via single-use injection device [Cohort 1] or delivery via a hand-held syringe from an SC Vial [Cohort 2]; 600 mg fixed dose) followed by four of the intravenous form of trastuzumab (Herceptin® [H IV]; 8 mg/kg loading, 6 mg/kg maintenance doses) in the adjuvant setting or vice versa every 3 weeks. Patients could have received H before randomisation. H was then continued to complete a total of 18 cycles, including any cycles received before randomisation. RESULTS: A total of 488 patients were randomised across both cohorts. After median follow-up of 36.1 months, 3-year EFS across both groups in the evaluable intention-to-treat population (467 patients) was 90.6% overall, 89.9% in Cohort 1, and 91.1% in Cohort 2. No new safety signals were identified during long-term follow-up, with only one cardiac serious adverse event in the safety population (483 patients). CONCLUSIONS: Three-year EFS data following H SC and H IV treatment are consistent with those reported by previous trials for H in the adjuvant setting. The overall safety profile during adjuvant treatment was as expected.

Therapeutic aims of drugs offering only progression-free survival are misunderstood by patients, and oncologists may be overly optimistic about likely benefits.

PURPOSE: The use of novel and often expensive drugs offering limited survival benefit in advanced disease is controversial. Treatment recommendations are influenced by patient characteristics and trial data showing overall response rates (ORR), progression-free survival (PFS) and overall survival (OS). PFS is frequently the primary outcome in licencing studies. PATIENTS AND METHODS: As part of a longitudinal study Assessing the 'VALue' to patients of PROgression Free Survival (AVALPROFS), oncologists completed checklists at baseline following consultations with patients. Questions probed perceived clinical benefits of the drugs to populations in general. Patients completed study-specific interview schedules at baseline, 6 weeks into treatment, and at withdrawal due to toxicity or progression. Patients also completed tumour- and treatment-specific quality of life questionnaires monthly for their time in the study. Only baseline results are reported here. RESULTS: Thirty-two UK oncologists discussed management options with 90 patients with heterogeneous advanced cancers. Oncologists' estimates of medical benefit in general from treatment varied between 10 and 80 %. They expected 46/90 (51 %) of their patients to derive some clinical benefit from the prescribed treatment but were either unsure or expected none for 44/90 (49 %). Predictions of life expectancy were variable but 62 % (56/90) of patients were expected to survive longer with treatment. A majority of patients 51/90 (57 %) had 'no idea' or were 'unclear' what PFS meant and 45/90 (50 %) thought extension of life was the primary therapeutic aim of treatment. CONCLUSION: Discussions between doctors and patients with metastatic disease about future management plans and likely therapeutic gains are challenging. Factors influencing decisions about putative benefits of novel drugs are often applied inconsistently can be overly optimistic and may even contradict published data.