Long-term outcomes of dual vs single HER2-directed neoadjuvant therapy in NSABP B-41.

BACKGROUND: The primary aim of this randomized neoadjuvant trial in operable, HER2-positive breast cancer, was to determine the efficacy on pathologic complete response (pCR) of substituting lapatinib (L) for trastuzumab (T) or adding L to T, in combination with weekly paclitaxel (WP) following AC. Results on pCR were previously reported. Here, we report data on planned secondary endpoints, recurrence-free interval (RFI) post-surgery, and overall survival (OS). METHODS: All patients received standard AC q3 weeks × 4 cycles followed by WP (80 mg/m2) on days 1, 8, and 15, q28 days × 4 cycles. Concurrently with WP, patients received either T (4 mg/kg load, then 2 mg/kg) weekly until surgery, L (1250 mg) daily until surgery, or weekly T plus L (750 mg) daily until surgery. Following surgery, all patients received T to complete 52 weeks of HER2-targeted therapy. 522 of 529 randomized patients had follow-up. Median follow-up was 5.1 years. RESULTS: RFI at 4.5 years was 87.2%, 79.4% (p = 0.34; HR = 1.37; 95% CI 0.80, 2.34), and 89.4% (p = 0.37; HR = 0.70; 0.37, 1.32) for arms T, L, and TL, respectively. The corresponding five-year OS was 94.8%, 89.1% (p = 0.34; HR = 1.46; 0.68, 3.11), and 95.8% (p = 0.25; HR = 0.58; 0.22, 1.51), respectively. Patients with pCR had a much better prognosis, especially in the ER-negative cohort: RFI (HR = 0.23, p < 0.001) and OS (HR = 0.28, p < 0.001). CONCLUSIONS: Although pCR, RFI, and OS were numerically better with the dual combination and less with L, the differences were not statistically significant. However, achievement of pCR again correlated with improved outcomes, especially remarkable in the ER-negative subset. CLINICAL TRIALS REGISTRATION: NCT00486668.

Comparison of Radiation With or Without Concurrent Trastuzumab for HER2-Positive Ductal Carcinoma In Situ Resected by Lumpectomy: A Phase III Clinical Trial.

PURPOSE: Preclinical studies report that trastuzumab (T) can boost radiotherapy (RT) effectiveness. The primary aim of the B-43 trial was to assess the efficacy of RT alone vs concurrent RT plus T in preventing recurrence of ipsilateral breast cancer (IBTR) in women with ductal carcinoma in situ (DCIS). PATIENTS AND METHODS: Eligibility: Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, DCIS resected by lumpectomy, known estrogen receptor (ER) and/or progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) status by centralized testing. Whole-breast RT was given concurrently with T. Stratification was by menopausal status, adjuvant endocrine therapy plan, and nuclear grade. Definitive intent-to-treat primary analysis was to be conducted when either 163 IBTR events occurred or all accrued patients were on study ≥ 5 years. RESULTS: There were 2,014 participants who were randomly assigned. Median follow-up time as of December 31, 2019, was 79.2 months. At primary definitive analysis, 114 IBTR events occurred: RT arm, 63 and RT plus T arm, 51 (hazard ratio [HR], 0.81; 95% CI, 0.56 to 1.17; P value = .26). There were 34 who were invasive: RT arm, 18 and RT plus T arm, 20 (HR, 1.11; 95% CI, 0.59 to 2.10; P value = .71). Seventy-six were DCIS: RT arm, 45 and RT plus T arm, 31 (HR, 0.68; 95% CI, 0.43 to 1.08; P value = .11). Annual IBTR event rates were: RT arm, 0.99%/y and RT plus T arm, 0.79%/y. The study did not reach the 163 protocol-specified events, so the definitive analysis was triggered by all patients having been on study for ≥ 5 years. CONCLUSION: Addition of T to RT did not achieve the objective of 36% reduction in IBTR rate but did achieve a modest but statistically nonsignificant reduction of 19%. Nonetheless, this trial had negative results. Further exploration of RT plus T is needed in HER2-positive DCIS before its routine delivery in patients with DCIS resected by lumpectomy.

Predictors of unmet needs in Chilean older people with dementia: a cross-sectional study.

BACKGROUND: The needs of people with dementia (PWD) have not been assessed in any Latin American country. Several European countries have already related unmet needs with quality of life, caregiver's age, burden, stress, anxiety and depression. The aim of this study was to identify met and unmet needs in Chilean older adults with dementia and to determine if those needs were associated with PWD's, their informal caregivers' and social factors. METHOD: This was a cross-sectional study. One-hundred and sixty-six informal caregivers and their care recipients were interviewed. PWD was assessed about cognitive function and their caregivers answered instruments about PWD's needs, functional status and behavioral and psychological symptoms. Caregiver's burden, depression, anxiety and social support were also evaluated. A stepwise multiple linear regression analysis was performed to determine predictors of unmet needs in Chilean PWD. RESULTS: The most frequent met needs were "Looking after home" (81.3%%), "Food" (78.9%) and "Selfcare" (75.3%). Most common unmet needs were "Daily living activities" (39.2%), "Company" (36.1%), and "Memory" (34.9%). Caregivers' lower age was correlated to a higher number of PWD's unmet needs (rs = -.216; p < 0.005). Higher PWD's dependence was associated with higher number of unmet needs (rs = .177; p < 0.05). The best predictors of unmet needs were caregivers' low level of social support, high burden, young age and high level of anxiety. CONCLUSION: It is necessary to address psychological and social needs of PWD. The fact that PWD's unmet needs were associated mostly with caregivers' factors, highlights the importance of considering both, the PWD and their informal caregivers as targets of institutional support. It is expected that recently launched national public policies decrease PWD's unmet needs by the provision of new services for them and their informal caregivers.

[Healthcare associated infections (HAI), antibiotic use and prevalence of multidrug-resistant bacteria (MDRO) in residents of long-term care facilities: the Frankfurt HALT plus MDRO project 2012]. / Nosokomiale Infektionen, systemischer Antibiotikaeinsatz und multiresistente Erreger bei Bewohnern von Altenpflegeheimen : Das Frankfurter HALT plus MRE-Projekt, 2012.

BACKGROUND: Residents of long-term care facilities (LTCF) are at risk of healthcare associated infections (HAI) and are often treated with antibiotics. In Germany a current HAI prevalence of 1.6 % and antibiotic use in 1.15% have been reported. However, data published on the current prevalence of multidrug-resistant organisms (MRDO) in LTCFs in Germany are scarce. Therefore, the prevalence of HAI, antibiotic use and presence of MDROs were investigated in LTCF residents in Frankfurt am Main, Germany. METHODS: A point prevalence study of HAI and antibiotic use according to the European HALT protocol (health care associated infections in long-term care facilities) was carried out; swabs from the nose, throat and perineum were analyzed for methicillin-resistant Staphylococcus aureus (MRSA), extended spectrum beta-lactamase producing enterobacteria (ESBL) and vancomycin-resistant enterococci (VRE). RESULTS: A total of 880 residents in 8 LTCFs were enrolled in the study in 2012. The study participants were 30% male, 46.7% were more than 85 years old, 70% exhibitied urinary or fecal incontinence, 11.4% had an indwelling urinary catheter and 0.1% a vascular catheter. Prevalence rates of HAI and of antibiotic use were 2.5 % and 1.5%, respectively. The prevalence of MDROs in 184 residents who agreed to being tested for MDROs was 9.2% MRSA, 26.7% ESBL and 2.7% VRE. CONCLUSION: The HAIs and antibiotic use were comparable to the German HALT data from 2010. Compared to other German studies there is a steadily increasing MRSA problem in German LTCFs. High and increasing ESBL rates have been detected in German LTCFs. Further studies are needed to confirm this trend, preferably encompassing molecular methods to study epidemiology.

Phase II trial of induction gemcitabine/CPT-11 followed by a twice-weekly infusion of gemcitabine and concurrent external beam radiation for the treatment of locally advanced pancreatic cancer.

PURPOSE: This phase II trial of induction irinotecan/gemcitabine followed by twice-weekly gemcitabine and upper abdominal radiation was initiated to determine the activity of this regimen in patients with unresectable pancreatic cancer. METHODS: Patients with locally advanced, nonmetastatic adenocarcinoma of the pancreas received 2 cycles of induction irinotecan (100 mg/m2 IV) and gemcitabine (1000 mg/2 IV) on days 1 and 8 of each 3-week cycle. Following the induction, patients without disease progression received gemcitabine administered twice weekly (40 mg/m2/day) for 5 weeks concurrent with upper abdominal radiation (50.4 Gy over 5.5 weeks). RESULTS: From April 2000 to August 2003, 20 patients were entered into this study, 17 of whom were evaluable for treatment response. Characteristics included a median age of 67 years (range, 44-87 years) and 14 men (70%). Grades III and IV hematologic toxicity occurred in 25% and 5% of patients respectively and was primarily thrombocytopenia. No grade IV gastrointestinal toxicities or deaths due to therapy were observed. All therapy was completed in 8 patients, 7 patients were removed due to progression, 2 due to toxicity, 2 refused further treatment, and 1 was removed per the treating physician. The median time to progression and median survival was 5.1 months (95% CI, 3.2-6.7) and 8.8 months (95% CI, 6.4-10.1) respectively. Four patients (20%) were alive at 12 and 18 months. CONCLUSION: Induction irinotecan/gemcitabine followed by twice-weekly gemcitabine and upper abdominal radiation is feasible in patients with locally advanced pancreatic cancer. This regimen, however, has only modest activity and should not be explored further.