The acceptability of exercise prehabilitation before cancer surgery among patients, family members and health professionals: a mixed methods evaluation.

PURPOSE: Exercise prehabilitation aims to increase preoperative fitness, reduce post-operative complications, and improve health-related quality of life. For prehabilitation to work, access to an effective programme which is acceptable to stakeholders is vital. The aim was to explore acceptability of exercise prehabilitation before cancer surgery among key stakeholders specifically patients, family members and healthcare providers. METHODS: A mixed-methods approach (questionnaire and semi-structured interview) underpinned by the Theoretical Framework of Acceptability was utilised. Composite acceptability score, (summation of acceptability constructs and a single-item overall acceptability construct), and median of each construct was calculated. Correlation analysis between the single-item overall acceptability and each construct was completed. Qualitative data was analysed using deductive and inductive thematic analysis. RESULTS: 244 participants completed the questionnaire and n=31 completed interviews. Composite acceptability was comparable between groups (p=0.466). Four constructs positively correlated with overall acceptability: affective attitude (r=0.453), self-efficacy (r=0.399), ethicality (r=0.298) and intervention coherence (r=0.281). Qualitative data confirmed positive feelings, citing psychological benefits including a sense of control. Participants felt flexible prehabilitation program would be suitable for everyone, identifying barriers and facilitators to reduce burden. CONCLUSION: Exercise prehabilitation is highly acceptable to key stakeholders. Despite some burden, it is a worthwhile and effective intervention. Stakeholders understand its purpose, are confident in patients' ability to participate, and regard it is an important intervention contributing to patients' psychological and physical wellbeing. IMPLICATIONS: •Introduction should be comprehensively designed and clearly presented, providing appropriate information and opportunity for questions. •Programmes should be patient-centred, designed to overcome barriers and address patients' specific needs and goals. •Service must be appropriately resourced with a clear referral-pathway.

Clinicogenomic factors and treatment patterns among patients with advanced non-small cell lung cancer with or without brain metastases in the United States.

BACKGROUND: This retrospective, real-world study evaluated the prevalence of brain metastases, clinicodemographic characteristics, systemic treatments, and factors associated with overall survival among patients with advanced non-small cell lung cancer (aNSCLC) in the US. We also described the genomic characterization of 180 brain metastatic specimens and frequency of clinically actionable genes. MATERIALS AND METHODS: De-identified electronic health records-derived data of adult patients diagnosed with aNSCLC between 2011 and 2017 were analyzed from a US-nationwide clinicogenomic database. RESULTS: Of 3257 adult patients with aNSCLC included in the study, approximately 31% (n = 1018) had brain metastases. Of these 1018 patients, 71% (n = 726) were diagnosed with brain metastases at initial NSCLC diagnosis; 57% (n = 583) of patients with brain metastases received systemic treatment. Platinum-based chemotherapy combinations were the most common first-line therapy; single-agent chemotherapies, epidermal growth factor receptor tyrosine kinase inhibitors, and platinum-based chemotherapy combinations were used in second line. Patients with brain metastases had a 1.56 times greater risk of death versus those with no brain metastases. In the brain metastatic specimens (n = 180), a high frequency of genomic alterations in the p53, MAPK, PI3K, mTOR, and cell-cycle associated pathways was observed. CONCLUSION: The frequency of brain metastases at initial clinical presentation and associated poor prognosis for patients in this cohort underscores the importance of early screening for brain metastasis in NSCLC. Genomic alterations frequently identified in this study emphasize the continued need for genomic research and investigation of targeted therapies in patients with brain metastases.

Treatment patterns and outcomes associated with sequential and non-sequential use of CDK4 & 6 inhibitors in patients with HR+, HER2- MBC in the real world.

PURPOSE: Cyclin Dependent Kinase 4 & 6 inhibitors (CDK4 & 6i) have transformed the management of HR+, HER2- metastatic breast cancer (MBC); however, the optimal sequence of these treatments and other systemic therapies for MBC remains unclear. METHODS: This study analyzed electronic medical records from the ConcertAI Oncology Dataset. US patients who received abemaciclib and at least one other systemic line of therapy (LOT) for HR+, HER2- MBC were eligible. Treatment sequences were grouped, and data for two pairs of groups are presented herein (N = 397): Group 1 (1L CDK4 & 6i to 2L CDK4 & 6i) vs. Group 2 (1L CDK4 & 6i to 2L non-CDK4 & 6i), and Group 3 (2L CDK4 & 6i to 3L CDK4 & 6i) vs. Group 4 (2L CDK4 & 6i to 3L non-CDK4 & 6i). Time-to-event outcomes (PFS and PFS-2) were analyzed using Kaplan-Meier method and Cox proportional hazard regression. RESULTS: In the total cohort of 690 patients, the most prevalent sequence was 1L CDK4 & 6i to 2L CDK4 & 6i (n = 165). For the 397 patients across Groups 1-4, sequential CDK4 & 6i demonstrated numerically longer PFS and PFS-2 versus non-sequential CDK4 & 6i. Adjusted results demonstrate that patients in Group 1 demonstrated significantly longer PFS (p = 0.05) versus Group 2. CONCLUSIONS: Although retrospective and hypothesis-generating, these data demonstrate numerically longer outcomes in the subsequent LOT associated with sequential CDK4 & 6i treatment.

Identifying outcomes reported in exercise interventions in oesophagogastric cancer survivors: a systematic review.

BACKGROUND: Research investigating exercise interventions in oesophagogastric cancer survivors is sparse, and the outcomes are varied. The aim of this systematic review is to identify the domains and outcomes reported in exercise interventions in oesophagogastric cancer survivors to be included in a Delphi study, with a view to informing the development of a core outcome set (COS). METHODS: EMBASE, PubMed, CINHAL, Cochrane Library, SCOPUS, and PEDro were searched up to March 2020 using a predefined search strategy. The outcomes identified during data extraction were categorised using the core areas outlined in the OMERACT Filter 2.0. RESULTS: Fourteen domains and 63 outcomes were identified. The most frequently reported outcomes were in the domains of quality of life using the EORTC-QLQ-C30 questionnaire and the relevant disease-specific modules (100%), exercise capacity/fitness/physical function (100%), anthropometrics (83.33%), physical activity (66.67%), and biomarker analysis (50%). CONCLUSION: This systematic review quantifies and describes the domains and outcomes examined in exercise interventions in oesophagogastric cancer survivors. Some inconsistency exists within the domains and outcomes used, and little attention was given to nutritional or economic endpoints. In order to develop a COS, a Delphi consensus process with key stakeholders is needed to identify the relevant domains and outcomes for inclusion.

Treatment patterns and health care resource use in patients receiving multiple lines of therapy for metastatic squamous cell carcinoma of the head and neck in the United Kingdom.

This study evaluated the patterns of care and health care resource use (HCRU) in patients with metastatic squamous cell carcinoma of the head and neck (SCCHN) who received ≥3 lines of systemic therapy in the United Kingdom (UK). Oncologists (n = 40) abstracted medical records for patients with metastatic SCCHN who initiated third-line systemic therapy during 1 January 2011-30 August 2014 (n = 220). Patient characteristics, treatment patterns and SCCHN-related HCRU were summarised descriptively for the metastatic period; exploratory multivariable regression analyses were conducted on select HCRU outcomes. At metastatic diagnosis, most patients had an Eastern Cooperative Oncology Group performance status (PS) of 0/1 (95%). For patients with PS 0/1, the most common first-line treatment was cisplatin+5-fluorouracil (5-FU); docetaxel was the most common second- and third-line treatment. For patients with PS ≥ 2, the most common first-, second-, and third-line treatments were carboplatin+5-FU, cetuximab, and methotrexate, respectively. Most patients received supportive care during (85%) and after (89%) therapy. This study provides useful information, prior to the availability of immunotherapy, on patient characteristics, treatment patterns, HCRU, and survival in a real-world UK population with metastatic SCCHN receiving ≥3 lines of systemic therapy. Patterns of care and HCRU varied among patients with metastatic SCCHN; specific systemic therapies varied by patient PS.

Phase II evaluation of LY2603618, a first-generation CHK1 inhibitor, in combination with pemetrexed in patients with advanced or metastatic non-small cell lung cancer.

Introduction LY2603618 is a selective inhibitor of checkpoint kinase 1 (CHK1) protein kinase, a key regulator of the DNA damage checkpoint, and is predicted to enhance the effects of antimetabolites, such as pemetrexed. This phase II trial assessed the overall response rate, safety, and pharmacokinetics (PK) of LY2603618 and pemetrexed in patients with non-small cell lung cancer (NSCLC). Methods In this open-label, single-arm trial, patients with advanced or metastatic NSCLC progressing after a prior first-line treatment regimen (not containing pemetrexed) and Eastern Cooperative Oncology Group performance status ≤2 received pemetrexed (500 mg/m(2), day 1) and LY2603618 (150 mg/m(2), day 2) every 21 days until disease progression. Safety was assessed using Common Terminology Criteria for Adverse Events v3.0. Serial blood samples were collected for PK analysis after LY2603618 and pemetrexed administration. Expression of p53, as measured by immunohistochemistry and genetic variant analysis, was assessed as a predictive biomarker of response. Results Fifty-five patients were enrolled in the study. No patients experienced a complete response; a partial response was observed in 5 patients (9.1 %; 90 % CI, 3.7-18.2) and stable disease in 20 patients (36.4 %). The median progression-free survival was 2.3 months (range, 0-27.1). Safety and PK of LY2603618 in combination with pemetrexed were favorable. No association between p53 status and response was observed. Conclusions There was no significant clinical activity of LY2603618 and pemetrexed combination therapy in patients with advanced NSCLC. The results were comparable with historical pemetrexed single-agent data, with similar safety and PK profiles being observed.

Patient-reported pain and other quality of life domains as prognostic factors for survival in a phase III clinical trial of patients with advanced breast cancer.

BACKGROUND: Patient-reported outcomes have been associated with survival in numerous studies across cancer types, including breast cancer. However, the Brief Pain Inventory-Short Form (BPI-SF) and the Rotterdam Symptom Checklist (RSCL) have rarely been investigated in this regard in breast cancer. METHODS: Here we describe a post hoc analysis of the prognostic effect of baseline scores of these instruments on survival in a phase III trial of patients with advanced breast cancer who received gemcitabine plus paclitaxel or paclitaxel alone after anthracycline-based adjuvant or neoadjuvant therapy. The variables for this analysis were baseline BPI-SF "worst pain" and BPI-SF "pain interference" scores, and four RSCL subscales (each transformed to 0-100). Univariate and multivariate Cox models were used, the latter in the presence of 11 demographic/clinical variables. Kaplan-Meier curves and log-rank tests were used to compare survival for patients by BPI-SF or RSCL scores. RESULTS: Of 529 randomized patients, 286 provided BPI-SF data and 336 provided RSCL data at baseline. Univariate analyses identified BPI-SF worst pain and pain interference (both hazard ratios [HR], 1.07 for a 1-point increase; both p ≤ 0.0061) and three of four RSCL subscales [activity level, physical distress, and health-related quality of life (HRQOL) (HR, 0.86-0.91 for 10-point increase all p ≤ 0.0104)], to have significant prognostic effect for survival. BPI-SF worst pain (p = 0.0342) and RSCL activity level (p = 0.0004) were prognostic in the multivariate analysis. Median survival for patients categorized by BPI-SF worst pain score was 23.8 (n = 91), 17.9 (n = 94) and 14.6 (n = 94) months for scores 0, 1-4, and 5-10, respectively (log-rank p = 0.0065). Median survival was 23.8 and 14.6 months for patients (n = 330) with above- and below-median RSCL activity level scores respectively (log-rank p < 0.0001). CONCLUSION: Pretreatment BPI-SF worst pain and RSCL activity scores provide distinct prognostic information for survival in patients receiving paclitaxel or gemcitabine plus paclitaxel for advanced breast cancer even after controlling for multiple demographic and clinical factors. TRIAL REGISTRATION: Clinicaltrials.gov, NCT00006459.

Comparison of demographics, treatment patterns, health care utilization, and costs among elderly patients with extensive-stage small cell and metastatic non-small cell lung cancers.

BACKGROUND: Limited data exist regarding real-world treatment patterns, resource utilization, and costs of extensive-stage small cell lung cancer (esSCLC) among elderly patients in the United States. While abundant data are available on treatment patterns in metastatic non-small cell lung cancer (mNSCLC), to our knowledge no data exist comparing costs and resource use between patients with esSCLC or mNSCLC. METHODS: We retrospectively analyzed administrative claims data (2000-2008) of patients aged ≥65 years from the linked Surveillance, Epidemiology and End Results (SEER)-Medicare database. Patients were selected on the basis of having newly diagnosed esSCLC (n=5,855) or mNSCLC (n=24,090) during 1/1/2000-12/31/2005, and were required to have received cancer-directed therapy. Survival and other measures were compared between esSCLC and mNSCLC patients using Kaplan-Meier log-rank and univariate chi-square and t-tests. Study measures were followed from first diagnosis date of either esSCLC or mNSCLC until the earlier of death or end of the database. RESULTS: Survival between the cohorts did not differ significantly: mean of 10.4 months for esSCLC patients versus 11.1 months for mNSCLC; median survival was 7.4 months versus 5.9 months. A higher percentage of mNSCLC patients (vs. esSCLC) received radiation therapy (75.6% vs. 65.4%; P < 0.001) and surgery (13.6% vs. 7.8%; P < 0.001) during the metastatic disease period. Conversely, a higher percentage of esSCLC patients than mNSCLC patients received chemotherapy (85.5% vs. 60.3%; P < 0.001), red blood-cell transfusion (20.7% vs. 10.9%; P < 0.001), platelet transfusion (5.6% vs. 1.8%; P < 0.001), and growth-factor support (59.0% vs. 39.5%; P < 0.001). esSCLC patients incurred higher lifetime disease-related costs ($44,167 vs. $37,932; P < 0.001) and all-cause costs ($70,549 vs. $67,176; P < 0.001) than mNSCLC patients. CONCLUSIONS: Lifetime total and disease-related costs per patient were high. Increased use of chemotherapy, supportive care therapies (including growth factors), and disease-related hospitalizations were observed in esSCLC patients as compared with mNSCLC patients. Disease-related and all-cause costs for esSCLC also exceeded those of mNSCLC, except for hospice and skilled nursing services. Survival and per-patient costs for both groups underscore the unmet medical need for more effective therapies in patients with esSCLC or mNSCLC.

The prevalence of non-affective psychosis in refugee populations: A systematic review.

BACKGROUND: As we face the largest refugee crisis since World War Two, research is increasingly examining the impact of forced displacement. The risk of non-affective psychosis in refugees is evidenced to be significantly greater than non-refugees, and the role of pre-, peri- and post-migratory trauma and dissociation is increasingly implicated. AIMS: To determine the prevalence of non-affective psychosis in refugee populations. METHOD: PRISMA guidelines were followed. Three key databases (PubMed, PsychINFO and Web of Science), Google scholar and study references were searched. The full-text of 62 studies were screened and 23 studies were eligible for inclusion. A narrative synthesis was undertaken and the Quality Assessment Tool for Quantitative Studies was used to assess methodological quality. (PROSPERO registration CRD42019152170). RESULTS: The results were widely heterogeneous. The combined weighted average prevalence of non-affective psychosis in refugee populations was 0.9 %. Psychosis prevalence for individual psychotic symptoms was 28.4 %; 0.5 % for schizophrenia; 1.0 % for psychosis; 0.6 % for mixed psychotic disorders and 2.9 % for psychotic episodes. CONCLUSIONS: Variations in examined populations, diagnostic and prevalence classifications, and study designs and methodologies likely contributed to heterogeneity across the data. The findings highlight a greater need to provide more specialist mental health services and trauma-focused interventions, as well as transculturally sensitive assessment and treatment to address refugee vulnerability to psychosis. Future research should examine psychosis prevalence longitudinally and in refugees-only, address methodological bias and further examine the role of trauma and dissociation in refugee psychosis prevalence.

Clinical and Genomic Characteristics of Patients with Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer Following Progression on Cyclin-Dependent Kinase 4 and 6 Inhibitors.

PURPOSE: We explored the clinical and genomic characteristics of hormone receptor-positive (HR+), HER2-negative (HER2-) metastatic breast cancer (MBC) after progression on cyclin-dependent kinase 4 and 6 inhibitors (CDK4 and 6i) ± endocrine therapy (ET) to understand potential resistance mechanisms that may aid in identifying treatment options. EXPERIMENTAL DESIGN: Patients in the United States with HR+, HER2- MBC had tumor biopsies collected from a metastatic site during routine care following progression on a CDK4 and 6i ± ET (CohortPost) or prior to initiating CDK4 and 6i treatment (CohortPre) and analyzed using a targeted mutation panel and RNA-sequencing. Clinical and genomic characteristics were described. RESULTS: The mean age at MBC diagnosis was 59 years in CohortPre (n = 133) and 56 years in CohortPost (n = 223); 14% and 45% of patients had prior chemotherapy/ET, and 35% and 26% had de novo stage IV MBC, respectively. The most common biopsy site was liver (CohortPre, 23%; CohortPost, 56%). CohortPost had significantly higher tumor mutational burden (TMB; median 3.16 vs. 1.67 Mut/Mb, P < 0.0001), ESR1 alteration frequency (mutations: 37% vs. 10%, FDR < 0.0001; fusions: 9% vs. 2%, P = 0.0176), and higher copy-number amplification of genes on chr12q15, including MDM2, FRS2, and YEATS4 versus patients in the CohortPre group. In addition, CDK4 copy-number gain on chr12q13 was significantly higher in CohortPost versus CohortPre (27% vs. 11%, P = 0.0005). CONCLUSIONS: Distinct mechanisms potentially associated with resistance to CDK4 and 6i ± ET, including alterations in ESR1 and amplification of chr12q15 and CDK4 copy-number gain, were identified.

Real-World Analysis of Clinical and Demographic Characteristics, Treatment Patterns, and Outcomes in Predominantly Older Patients with HR+/HER2- Metastatic Breast Cancer Receiving Abemaciclib in Routine Clinical Practice.

INTRODUCTION: Hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) is the most frequently diagnosed metastatic breast cancer (mBC) subtype. Combinations of endocrine therapy (ET) with cyclin-dependent kinase 4/6 inhibitors (CDK4 & 6is) improve outcomes compared with ET alone. The efficacy and safety of abemaciclib among patients with HR+/HER2- mBC has been demonstrated in the MONARCH clinical trials; however, there is a paucity of real-world evidence, particularly in older patients. METHODS AND MATERIALS: This retrospective cohort study analyzed the electronic medical record data/charts of adult patients with HR+/HER2- mBC receiving abemaciclib in US-based community oncology settings (1 September 2017 to 30 September 2019). Patients with other primary malignancies, clinical trial enrollment, and incomplete charts were excluded. Patient characteristics, treatment attributes and patterns, and real-world outcomes (clinical benefit rate [CBR] and stable disease among patients with response data available, time to chemotherapy [TTC], time to treatment discontinuation [TTD], and progression-free survival [PFS]) were summarized. Multivariable models evaluated the association between demographic/clinical characteristics and outcomes. RESULTS: Of the 448 final patients, 99% were female, with a median age of 67 years (25% were ≥ 75 years) and median follow-up of 11 months; most (60%) initiated abemaciclib within 2 years of mBC diagnosis. Patients received a median of 1 (P25 = 0, P75 = 3) prior line of therapy for mBC before abemaciclib, including other CDK4 & 6is (48%) and prior chemotherapy (31%); most (57%) had visceral disease. The CBR for the overall population was 53%, with 48% achieving stable disease. The median TTC was not reached; median TTD was 249 days (95% confidence interval [CI]: 202, 304). The median PFS was 329 days (95% CI 266, 386). The discontinuation rate of abemaciclib owing to adverse events (30%) trended higher with age (years) (P = 0.027): 18-49 (n = 42; 19%), 50-64 (n = 155; 25%), 65-74 (n = 138; 32%), 75-84 (n = 82; 37%), ≥ 85 (n = 31; 49%); only 23% of patients overall had a dose hold or reduction prior to discontinuation. CONCLUSIONS: These patients were older than those in the MONARCH studies with substantial visceral disease, and prior chemotherapy and CDK4 & 6i use. Discontinuation rates were higher than in previous real-world studies (11.9%), highlighting the need for proactive management to optimize outcomes, particularly in older patients with mBC.

Characteristics and Outcomes in Cases of US Male Patients with Metastatic Breast Cancer Receiving Abemaciclib in Routine Clinical Practice.

INTRODUCTION: Breast cancer in males constitutes approximately 1% of all breast cancer cases globally. Despite extensive treatment experience with abemaciclib in women with metastatic breast cancer (MBC), real-world evidence in male MBC is lacking. METHODS: This analysis was a part of a broader, retrospective study that analyzed electronic medical records and charts of 448 men and women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) MBC who initiated an abemaciclib-containing regimen from January 2017 through September 2019. Data were collected from the Florida Cancer Specialists & Research Institute and the Electronic Medical Office Logistics Health Oncology Warehouse Language™ databases and summarized descriptively. Real-world best response was described: complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). RESULTS: Data for six male patients with MBC who were treated with abemaciclib in combination with an aromatase inhibitor (AI) or fulvestrant are presented. Four patients were aged ≥ 75 years, and four patients had ≥ 3 metastatic sites, including visceral involvement. Abemaciclib was initiated in/after third-line (≥ 3L) in four patients, and patients had history of treatment with AI (n = 4), chemotherapy (n = 3), and/or prior cyclin-dependent kinase 4 and 6 inhibitors (n = 2) in the metastatic setting. Abemaciclib + fulvestrant was the most common abemaciclib-containing regimen (n = 4). Best response was documented in four patients: 1 each with CR, PR, SD, and PD. CONCLUSION: Prevalence of male MBC in this dataset was consistent with expected prevalence in the broader population. Most male patients received an abemaciclib-containing regimen in ≥ 3L, with anti-cancer activity observed despite heavy metastatic burden and prior treatments in a metastatic setting.

Updating a Healthcare System-wide Clinical Pathway for Managing Chest Pain and Acute Coronary Syndromes.

Clinical pathways are useful tools for conveying and reinforcing best practices to standardize care and optimize patient outcomes across myriad conditions. The NewYork-Presbyterian Healthcare System has utilized a clinical chest pain pathway for more than 20 years to facilitate the timely recognition and management of patients presenting with chest pain syndromes and acute coronary syndromes. This chest pain pathway is regularly updated by an expanding group of key stakeholders, which has extended from the Columbia University Irving Medical Center to encompass the entire regional healthcare system, which includes 8 hospitals. In this 2023 update of the NewYork-Presbyterian clinical chest pain pathway, we present the key changes to the healthcare system-wide clinical chest pain pathway.

Physical Therapists in Oncology Settings: Experiences in Delivering Cancer Rehabilitation Services, Barriers to Care, and Service Development Needs.

OBJECTIVE: Physical therapist-delivered rehabilitation aims to manage the side effects of cancer and its treatments. Although access to cancer rehabilitation is not yet a standard of care in many countries, physical therapists practice in many types of cancer services with different cancer populations. The purpose of this study was to explore the experiences of physical therapists in cancer care practice with regard to their role, the factors influencing service delivery and development, and physical therapists' professional development needs. METHODS: In this qualitative study with semistructured interviews, physical therapists in cancer care settings in the Republic of Ireland were interviewed via telephone. Participants (n = 17) represented a variety of clinical settings and roles. Two researchers performed thematic analysis of transcriptions using a semantic, inductive approach. Key themes and codes were identified and illustrative quotes were selected. RESULTS: Six main themes were found: the need for more services, barriers to service development and delivery, a lack of awareness of the role of physical therapy, facilitators to service development, goals for the future of oncology physical therapy, and training needs of staff. CONCLUSIONS: Physical therapists provide valuable interventions across the spectrum of cancer care but experience barriers to the delivery and development of services. Investment in oncology physical therapy and developing international standards of care will allow physical therapists to meet the rehabilitation needs of survivors of cancer. IMPACT: As international guidelines increasingly recommend development of cancer rehabilitation programs, it is important to understand physical therapists' experiences of working in cancer care to assist in the development of effective oncology physical therapy services. This study demonstrates that physical therapist-led cancer rehabilitation services need investment and public promotion to enable the provision of optimal services to all patients with cancer and to meet standards of care.

Real-World Patient Characteristics, Utilization Patterns, and Outcomes of US Patients with HR+, HER2- Metastatic Breast Cancer Treated with Abemaciclib.

BACKGROUND: Abemaciclib is the most recent oral cyclin-dependent kinase 4 and 6 inhibitor (CDK4 & 6i) to receive US Food and Drug Administration (FDA) approval to treat hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer (MBC). Administrative claims data were used to describe patient characteristics and select clinical and economic outcomes in US patients treated in routine clinical practice. Prior analyses from electronic health records data indicate approximately 25% of patients received either palbociclib or ribociclib for MBC before initiating abemaciclib treatment; this work further explored these findings and associated outcomes. METHODS: This retrospective study analyzed medical and pharmacy claims from the IBM® MarketScan® Research Databases between 1 January 2007 to 31 January 2020. Patients with HR+, HER2- MBC newly initiating abemaciclib between 1 September 2017 and 31 October 2019 were included and grouped by concomitant therapy (+aromatase inhibitor (AI), +fulvestrant (F), 200 mg abemaciclib monotherapy (Mono), or +other), and outcomes were analyzed by prior CDK4 & 6i use. Patient and treatment characteristics were summarized with descriptive statistics. Kaplan-Meier methods assessed time-to-discontinuation (TTD; i.e., persistency) and time-to-chemotherapy (TTC). Adherence (defined by the medication possession ratio) and drug wastage were determined. RESULTS: This analysis included 454 patients (mean age 57.7 years), with 35.0% (n = 159) in the +F group, 29.3% (n = 133) in the +AI group, 10.4% (n = 47) in the 200 mg Mono group, and 25.3% (n = 115) in the +other group. Prior chemotherapy and CDK 4 & 6i use were present in 23.8% and 49.8% of all patients, respectively. Visceral metastases were present at abemaciclib initiation in 50.4% in the +AI group; 49.7% in the +F group; and 55.3% in the 200 mg Mono group. Liver metastases were present in 33.7% of the overall population. Among patients without prior CDK4 & 6i use, the median TTD for patients receiving abemaciclib + AI was not reached [95% CI 430-not reached (NR) days], abemaciclib + F [531 days (95% CI 281-NR)], and abemaciclib mono [141 days (95% CI 80-NR)]. Median TTC for abemaciclib + AI and abemaciclib + F groups were not reached and the median TTC for abemaciclib mono was 535 days (95% CI 181-NR). Medication adherence was 88.7% and medication wastage costs among those with at least one dose modification were $808.12 and $452.2 per patient per month based on amount paid and wholesale acquisition cost (WAC), respectively. Mean length of follow-up for all patients was 350 days (SD 187). CONCLUSION: These real-world data complement clinical trial results by examining abemaciclib use among patients treated in routine clinical practice. The sizeable number of patients treated with prior CDK4 & 6i, chemotherapy, and/or visceral metastases at abemaciclib initiation suggest that many patients had very advanced disease and/or were in later stages of their treatment. These data confirm a higher percentage of patients treated with previous CDK4 & 6i than reported previously, reinforcing the importance of the ongoing, prospective clinical trials evaluating outcomes following progression on CDK4 & 6i.

Real world incidence and management of adverse events in patients with HR+, HER2- metastatic breast cancer receiving CDK4 and 6 inhibitors in a United States community setting.

OBJECTIVE: To examine the real-world incidence and management of select adverse events (AEs) among female patients with hormone receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC), receiving a cyclin-dependent kinase 4 and 6 (CDK4 and 6) inhibitor (palbociclib, abemaciclib, or ribociclib). METHODS: This retrospective study analyzed data from the US Oncology Network iKnowMed electronic health record database for 396 patients with an initial MBC diagnosis on/after 1 January 2014 and receipt of first CDK4 and 6 regimen between 1 January 2017 and 31 December 2018. In this descriptive study, the proportion of patients who experienced select AEs and associated dose modifications or discontinuations were reported. The occurrence of select healthcare resource utilization categories was also reported. RESULTS: Median follow-up time was 451, 262, and 355 days for patients in the palbociclib, abemaciclib, and ribociclib cohorts, respectively. The most common AEs were neutropenia (palbociclib, 44.8%; abemaciclib, 10.6%; ribociclib, 36.3%), diarrhea (palbociclib, 8.0%; abemaciclib, 43.0%; ribociclib, 8.8%), and fatigue (palbociclib, 12.9%; abemaciclib, 17.6%; ribociclib, 16.5%). AEs resulted in a treatment hold among 91 (23.0%), a dose reduction among 86 (21.7%), and permanent discontinuation among 48 (12.1%) patients overall. CONCLUSIONS: This real-world study provides insight into the occurrence of AEs which varied by CDK4 and 6 inhibitor. Compared to clinical trials, frequencies of AEs were numerically lower but dose reductions due to AEs were numerically higher. It is possible these differences reflect proactive management of AEs on the part of clinicians to help patients remain on therapy.

Cyclin-dependent kinase 4 and 6 inhibitors (CDK4 and 6 inhibitors) have changed the landscape for the treatment of metastatic breast cancer (MBC) among patients who are hormone receptor positive (HR+) and human epidermal growth factor receptor 2 negative (HER2−). An understanding of the real-world management of adverse events (AEs) will help optimize treatment strategies. Here, data from the US Oncology Network electronic health record database for 396 HR+, HER2−, MBC patients receiving a CDK4 and 6 inhibitor were examined to describe the proportion of patients who experienced select AEs and the associated outcomes of these AEs. Compared to clinical trials, frequencies of AEs were numerically lower but dose reductions due to AEs were numerically higher. It is possible that these differences reflect a proactive management of AEs on the part of clinicians to help patients remain on therapy.

Telehealth Delivery of a Multi-Disciplinary Rehabilitation Programme for Upper Gastro-Intestinal Cancer: ReStOre@Home Feasibility Study.

BACKGROUND: Telehealth has enabled access to rehabilitation throughout the pandemic. We assessed the feasibility of delivering a multi-disciplinary, multi-component rehabilitation programme (ReStOre@Home) to cancer survivors via telehealth. METHODS: This single-arm mixed methods feasibility study recruited participants who had completed curative treatment for oesophago-gastric cancer for a 12-week telehealth rehabilitation programme, involving group resistance training, remotely monitored aerobic training, one-to-one dietetic counselling, one-to-one support calls and group education. The primary outcome was feasibility, measured by recruitment rates, attendance, retention, incidents, acceptability, Telehealth Usability Questionnaire (TUQ) and analysis of semi-structured interviews. RESULTS: Characteristics of the twelve participants were: 65.42 ± 7.24 years; 11 male; 10.8 ± 3.9 months post-op; BMI 25.61 ± 4.37; received neoadjuvant chemotherapy 7/12; received adjuvant chemotherapy 4/12; hospital length of stay 16 days (median). Recruitment rate was 32.4%, and retention rate was 75%. Mean attendance was: education 90%; dietetics 90%; support calls 84%; resistance training 78%. Mean TUQ score was 4.69/5. Adaptations to the planned resistance training programme were required. Participants reported that ReStOre@Home enhanced physical and psychological wellbeing, and online delivery was convenient. Some reported a preference for in-person contact but felt that the online group sessions provided adequate peer support. CONCLUSION: Telehealth delivery of ReStOre@Home was most feasible in individuals with moderate to high levels of digital skills. Low level of digitals skills was a barrier to recruitment and retention. Participants reported high levels of programme adherence and participant satisfaction. Adaptations to future programmes, including introducing elements of in-person contact, are required.

Preoperative high intensity interval training for oncological resections: A systematic review and meta-analysis.

Exercise prehabilitation prior to major surgery targets a reduction in postoperative complications through improved conditioning and respiratory function. However its effectiveness in cancer surgery is unclear. The objective of this review was to determine if preoperative high-intensity interval training (HIIT) improves preoperative fitness in patients scheduled for oncologic resection, and whether postoperative complications are impacted. METHODS: CINAHL, AMED, PEDro, EMBASE, The Cochrane Library and PubMed/MEDLINE were searched until April 2021 using predefined search strategy and accompanied by manual forward and backwards citation review. Screening of titles, abstracts, full-texts, data extraction, risk of bias assessment and methodologic quality was performed independently by two reviewers. Mean difference (MD) with 95% confidence intervals (CI) was compared and heterogeneity assessed using Chi Squared Test and I2 statistic. Six randomised controlled trials (RCTs) were included in the systematic review. Interventions prescribed bouts of high-intensity exercise [80-115% peak work rate (WRp)] interspaced with low-intensity (rest-50% WRp) exercise. The meta-analysis included five RCTs reporting peak oxygen consumption (VO2peak). Preoperative HIIT did not result in significantly higher VO2peak in comparison to usual care or moderate intensity exercise (MD 0.83, 95%CI-0.51-2.17) kg/ml/min, p = 0.12). Studies were insufficiently powered with respect to postoperative complications, but there is no evidence of significant impact. No adverse events occurred and high adherence rates were reported. Results of this systematic review and meta-analysis demonstrate there is insufficient evidence to support HIIT as a method of improving preoperative fitness prior to oncologic resection. Further work is needed to determine if specific HIIT parameters can be adapted to improve efficacy over short time-frames.

Clinical Characteristics, Treatments, and Concurrent Mutations in Non-Small Cell Lung Cancer Patients With NF1 Mutations.

OBJECTIVES: Metastatic non-small cell lung cancer (mNSCLC) is characterized by complex genomic alterations. NF1 mutations may confer distinct clinical characteristics within NSCLC, and real-world evidence on concurrent mutations, treatment patterns, and health outcomes is lacking. MATERIALS AND METHODS: This retrospective study was performed in patients with mNSCLC treated in the Flatiron Health network who underwent the FoundationOne tumor-sequencing. Anticancer therapies, concurrent mutations, real-world progression-free survival (rwPFS), and overall survival (OS) were assessed. RESULTS: Of the 1663 patients, 103 patients were identified with NF1 mutation. Concurrent mutations with Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (16.5%) and epidermal growth factor receptor fusion (6.8%) were the most frequent. In patients with NF1 mutation only (n = 57), 42% were women, 86% patients had smoking history, and 70% had non-squamous cell carcinoma type. Most (51%) of the patients with NF1 mutations received a single line of therapy versus other mutations and the overall treated population (44%). Platinum-based chemotherapy was the predominant first-line therapy, with programmed cell death-1/programmed cell death-ligand-1 inhibitors as subsequent lines of therapy. The NF1 mutation only group had numerically the shortest median rwPFS (82 days) than other mutation groups. Median OS for the NF1 mutation group in first, second, and third lines of therapy was 321, 498, and 210 days, respectively. CONCLUSIONS: NF1 mutations confer distinct clinical characteristics in patients with mNSCLC. These patients may have different trajectories for progression and survival than seen for other mutations, experience less systemic therapy after first-line therapy, and may have shorter survival.

Treatment patterns, adverse events, and direct and indirect economic burden in a privately insured population of patients with HR+/HER2- metastatic breast cancer in the United States.

BACKGROUND: Real-world evidence specific to HR+/HER2- metastatic breast cancer (MBC) prior to introduction of CDK4/6 inhibitors is limited. In an effort to provide context for the introduction of new treatments, we assessed treatment patterns, adverse events, productivity loss, and direct/indirect economic burden in a privately insured population of patients with HR+/HER2- MBC. RESEARCH DESIGN AND METHODS: Using a retrospective cohort design, patients aged 18-64 years, selected from MarketScan databases (2007-2014), were analyzed using descriptive and multivariable methods. RESULTS: Among 5,563 eligible patients, endocrine therapy was the most common first-line (1L) therapy; its utilization trended downward from 63% (1L) to 23% (4L), with a simultaneous increase in chemotherapy use, 25% (1L) to 50% (4L). Two hundred and seventy-eight unique treatment regimens were used in the 1L setting. The average per patient monthly all-cause costs were $14,424. The 12-month indirect costs for short-term disability were substantially higher in MBC patients ($10,397) than in matched noncancer patients ($394). CONCLUSION: The increasing use of chemotherapy as patients progressed to second and later lines and the substantial direct/indirect economic burden underscore an unmet need. The high number of 1L regimens highlights significant heterogeneity and a lack of consensus related to the management of HR+/HER2- MBC in routine practice.