Epirubicin With Cyclophosphamide Followed by Docetaxel With Trastuzumab and Bevacizumab as Neoadjuvant Therapy for HER2-Positive Locally Advanced Breast Cancer or as Adjuvant Therapy for HER2-Positive Pathologic Stage III Breast Cancer: A Phase II Trial of the NSABP Foundation Research Group, FB-5

Background The purpose of this study was to determine the cardiac safety and clinical activity of trastuzumab and bevacizumab with docetaxel after epirubicin with cyclophosphamide (EC) in patients with HER2-positive locally advanced breast cancer (LABC) or pathologic stage 3 breast cancer (PS3BC). Patients and Methods Patients received every 3 week treatment with 4 cycles of EC (90/600 mg/m2) followed by 4 cycles of docetaxel (100 mg/m2). Targeted therapy with standard-dose trastuzumab with bevacizumab 15 mg/kg was given for a total of 1 year. Coprimary end points were (1) rate of cardiac events (CEs) in all patients defined as clinical congestive heart failure with a significant decrease in left ventricular ejection fraction or cardiac deaths; and (2) pathologic complete response (pCR) in breast and nodes in the neoadjuvant cohort. An independent cardiac review panel determined whether criteria for a CE were met. Results A total of 105 patients were accrued, 76 with LABC treated with neoadjuvant therapy and 29 with PS3BC treated with adjuvant therapy. Median follow-up was 59.2 months. Among 99 evaluable patients for cardiac safety, 4 (4%; 95% confidence interval [CI], 1.1%-10.0%) met CE criteria. The pCR percentage in LABC patients was 46% (95% CI, 34%-59%). Five-year recurrence-free survival (RFS) and overall survival (OS) for all patients was 79.9% and 90.8%, respectively. Conclusion The regimen met predefined criteria for activity of interest with an acceptable rate of CEs. Although the pCR percentage was comparable with chemotherapy regimens with trastuzumab alone the high RFS and OS are of interest in these high-risk populations

Manual Scalp Cooling in Early Stage Breast Cancer: Value of Caretaker Training and Patient-Reported Experience to Optimize Efficacy and Patient Selection

Title: Manual scalp cooling in early stage breast cancer: value of caretaker training and patient-reported experience to optimize efficacy and patient selection Authors: Manaz Rezayee1, BS Nicole Moxon1, RN Staci Mellinger1, RN Amanda Y. Seino1 Nicole E. Fredrich1 Tracy L. Kelly1 Susan Mulligan2, MA Patrick Rossi3, MD Ijeoma Uche1, MD Walter J. Urba1, MD PHD Alison K. Conlin1, MD MPH Janet Ruzich1, DO David B. Page1, MD Background: Alopecia is an emotionally distressing common adverse effect of curative-intent chemotherapy in early stage breast cancer.1–6 Although machine-based scalp cooling is effective for reduction of chemotherapy-associated alopecia in early stage breast cancer, availability is geographically limited.7–11 Manual cold-cap systems may also be effective and are available regardless of geographic location.12–14 We evaluated the feasibility of caretaker-administered cold-cap efficacy following structured standardized training, and utilized patient-reported subjective outcomes to develop a clinical tool to facilitate patient selection. Patients and Methods: A small pilot study (n=10) was conducted to evaluate the feasibility and efficacy of manual cold capping. Key eligibility criteria included: 1) no hair loss at baseline; 2) no pre-existing scalp condition; 3) planned curative-intent chemotherapy for early stage breast cancer and 4) availability of caretaker(s). Participants received standardized training and then performed the cold-cap procedure without assistance. The primary endpoint was post-treatment hair retention using Dean’s alopecia scale, with success defined as Results: Of the evaluable patients, 80% (n=8/10) met the primary efficacy endpoint (Dean’s scale 0-2) with 20% (n=2/10) trial failures due to pre-mature discontinuation. Manual cold-capping was worthwhile to 90% of patients (Was it Worth It? Questionnaire) and associated with favorable PROs. Patient interviews identified a number of themes shared by almost all patients, which were subsequently used to develop a questionnaire to aid patient-directed decision-making on whether to pursue manual cold-capping. Conclusion: This study affirms the safety and efficacy of manual cold-capping to reduce alopecia and demonstrates the importance of proper training and education to maximize efficacy. It also highlights the considerable costs and effort associated with cold-capping. Selected patients with early stage breast cancer may benefit subjectively from cold capping while the proposed clinical instrument can be used to facilitate an informed discussion between patient and provider.https://digitalcommons.psjhealth.org/cancer_institute_fellowships/1000/thumbnail.jp

Intracranial Efficacy and Survival With Tucatinib Plus Trastuzumab and Capecitabine for Previously Treated HER2-Positive Breast Cancer With Brain Metastases in the HER2CLIMB Trial

PURPOSE: In the HER2CLIMB study, patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer with brain metastases (BMs) showed statistically significant improvement in progression-free survival (PFS) with tucatinib. We describe exploratory analyses of intracranial efficacy and survival in participants with BMs. PATIENTS AND METHODS: Patients were randomly assigned 2:1 to tucatinib or placebo, in combination with trastuzumab and capecitabine. All patients underwent baseline brain magnetic resonance imaging; those with BMs were classified as active or stable. Efficacy analyses were performed by applying RECIST 1.1 criteria to CNS target lesions by investigator assessment. CNS-PFS (intracranial progression or death) and overall survival (OS) were evaluated in all patients with BMs. Confirmed intracranial objective response rate (ORR-IC) was evaluated in patients with measurable intracranial disease. RESULTS: There were 291 patients with BMs: 198 (48%) in the tucatinib arm and 93 (46%) in the control arm. The risk of intracranial progression or death was reduced by 68% in the tucatinib arm (hazard ratio [HR], 0.32; 95% CI, 0.22 to 0.48; CONCLUSION: In patients with HER2-positive breast cancer with BMs, the addition of tucatinib to trastuzumab and capecitabine doubled ORR-IC, reduced risk of intracranial progression or death by two thirds, and reduced risk of death by nearly half. To our knowledge, this is the first regimen to demonstrate improved antitumor activity against BMs in patients with HER2-positive breast cancer in a randomized, controlled trial

Abemaciclib in Combination With Endocrine Therapy for Patients With Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: A Phase 1b Study

Background Cyclin-dependent kinases (CDK) 4 and 6 regulate G1 to S cell cycle progression and are often altered in cancers. Abemaciclib is a selective inhibitor of CDK4 and CDK6 approved for administration on a continuous dosing schedule as monotherapy or as combination therapy with an aromatase inhibitor or fulvestrant in patients with advanced or metastatic breast cancer. This Phase 1b study evaluated the safety and tolerability, pharmacokinetics, and antitumor activity of abemaciclib in combination with endocrine therapy for metastatic breast cancer (MBC), including aromatase inhibitors (letrozole, anastrozole, or exemestane) or tamoxifen. Patients and Methods Women ≥18 years old with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) MBC were eligible for enrollment. Eligibility included measurable disease or non-measurable but evaluable bone disease by Response Evaluation Criteria in Solid Tumours (RECIST) v1.1, Eastern Cooperative Oncology Group performance status 0–1, and no prior chemotherapy for metastatic disease. Adverse events were graded by the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0 and tumor response were assessed by RECIST v1.1. Results Sixty-seven patients were enrolled and received abemaciclib 200 mg every 12 hours in combination with letrozole (Part A, n=20), anastrozole (Part B, n=16), tamoxifen (Part C, n=16), or exemestane (Part D, n=15). The most common treatment-emergent adverse events (TEAE) were diarrhea, fatigue, nausea, and abdominal pain. Grade 4 TEAEs were reported in five patients (one each with hyperglycemia, hypertension, neutropenia, procedural hemorrhage, and sepsis). There was no effect of abemaciclib or endocrine therapy on the pharmacokinetics of any combination study drug. Across all treated patients, the median progression-free survival was 25.4 months (95% confidence interval: 18.0, 35.8). The objective response rate was 38.9% in 36 patients with measurable disease. Conclusions Abemaciclib in combination with multiple endocrine therapy options exhibited manageable safety and promising antitumor activity in patients with HR+, HER2- MBC. Clinical Trial Registration https://clinicaltrials.gov/, identifier NCT0205713

Association of nutrition with psychological health and quality of life among older adults with advanced cancer

Research Funding U.S. National Institutes of Health U.S. National Institutes of Health Background: Impaired nutrition is associated with greater treatment toxicity and reduced overall survival in patients with advanced cancer. We aimed to evaluate the association of impaired nutrition with psychological health and quality of life among older adults with advanced cancer who were starting cancer treatment with palliative intent. Methods: This secondary analysis was performed on baseline data from a nationwide cluster randomized clinical trial (ClinicalTrials.gov identifier: NCT02107443; PI: Mohile; funding NCI UG1CA189961). Adults age ≥70 with advanced cancer and≥1 geriatric assessment impairment were enrolled from 2014 to 2017. Patients with BMI \u3c 21 kg/m2, \u3e 10% involuntary weight loss in the past 6 months, or Mini Nutritional Assessment Short Form (MNA-SF) score of ≤11 were considered to have impaired nutrition. We used separate multivariable linear regressions to evaluate the association of impaired nutrition with each measure of psychological health and quality of life, which included Geriatric Depression Scale (GDS-15, range 0-15), Generalized Anxiety Disorder-7 (GAD-7, range 0-21), NCCN Distress Thermometer (NCCN DT, range 0-10) and Functional Assessment of Cancer Therapy-General (FACT-G, range 0-108). Analyses were adjusted for baseline patient demographics, clinical characteristics, and geriatric assessment. Results: Among 541 patients, mean age was 77 (range 70-96) and 60% had impaired nutrition. Among the 326 patients with impaired nutrition, 95% had MNA-SF ≤11, 23% had \u3e 10% weight loss in the last six months, and 20% had BMI \u3c 21 kg/m2. Mean baseline GDS-15 was 3.1 (standard deviation [SD] 2.7), GAD-7 was 2.9 (SD 4.0), NCCN DT was 2.9 (SD 2.7), and FACT-G was 80 (SD 14). In the adjusted model, compared to those with normal nutrition, older adults with impaired nutrition had greater depression (mean 0.65 points higher on the GDS-15, p \u3c 0.01) and lower quality of life (mean 6.0 points lower on the FACT-G, p \u3c 0.01). There was insufficient evidence of an association between nutrition and anxiety (β = 0.67, p = 0.06) or distress (β = 0.26, p = 0.28). Conclusions: Recognition of malnutrition by oncology providers is crucial for older adults with advanced cancer. Impaired nutrition is associated with greater depression and lower quality of life among older adults with advanced cancer. Tailored resources to improve psychological health and quality of life are needed to support older adults with impaired nutrition receiving cancer treatment

Effects of yoga, cognitive behavioral therapy, and a behavioral placebo on sleep: A nationwide multicenter phase III RCT in cancer survivors.

Research Funding: U.S. National Institutes of Health Background:Patients commonly experience impaired sleep throughout cancer treatment and for years into survivorship. Impaired sleep may mediate other cancer-related symptoms and can lead to the inability to complete daily activities and lower quality of life. More effective non-pharmacological treatment options for impaired sleep are needed. We conducted a nationwide, multicenter, phase III randomized controlled trial (RCT) comparing the effects of yoga (Yoga for Cancer Survivors; YOCAS), cognitive behavioral therapy for insomnia (CBT-I), and a behavioral placebo on impaired sleep in cancer survivors.Methods:This RCT was conducted via the URCC NCORP Research Base. Participants were cancer survivors 2-60 months post-treatment with insomnia. They were randomized to 1) YOCAS (75-min session biweekly for 4 wks), 2) CBT-I (90-min session weekly for 8 wks), and 3) behavioral placebo (survivorship health education per ASCO guidelines; 75-min session biweekly for 4 wks). Sleep efficiency, sleep duration, wake after sleep onset (WASO), and sleep latency were assessed via actigraphy at baseline and post-intervention. Actigraphs were worn on the non-dominant wrist 24 hours a day for 7 days. Linear mixed models were used to assess intervention effects on sleep outcomes.Results:740 survivors were enrolled (93% female, mean age 56±11 years, 73% breast cancer). Results revealed significant group differences among survivors in the 3 arms in sleep efficiency, sleep duration, and WASO (all p\u3c0.05), but not in sleep latency (p\u3e0.05). YOCAS and CBT-I subjects maintained sleep efficiency (mean change= -0.8% and -0.03%, respectively, all p\u3e0.05) while behavioral placebo subjects significantly reduced sleep efficiency (mean change= -3.4%, p\u3c0.01). When controlling for baseline, YOCAS and CBT-I subjects demonstrated better sleep efficiency compared to behavioral placebo subjects at post-intervention (all p\u3c0.05). YOCAS subjects also maintained sleep duration (mean change= -3.5 minutes, p\u3e0.05) while CBT-I and behavioral placebo subjects significantly reduced sleep duration (mean change= -20.3 minutes and -26.6 minutes, respectively, all p\u3c0.01). When controlling for baseline, YOCAS subjects demonstrated longer sleep duration compared to CBT-I and behavioral placebo subjects at post-intervention (all p\u3c0.05). There were no significant within-group changes in WASO over time in the 3 arms. When controlling for baseline, CBT-I subjects demonstrated a trend toward lower WASO compared to YOCAS (p=0.07) and behavioral placebo (p=0.05) subjects at post-intervention.Conclusions:Both YOCAS and CBT-I maintained sleep efficiency and/or sleep duration among cancer survivors. Oncologists should consider prescribing yoga and CBT-I for treating impaired sleep in cancer survivors. Funding: NCI UG1CA189961, R01CA181064, T32CA102618. Clinical trial information: NCT0261336