Abemaciclib in combination with pembrolizumab for HR+, HER2- metastatic breast cancer: Phase 1b study.

This nonrandomized, open-label, multi-cohort Phase 1b study (NCT02779751) investigated the safety and efficacy of abemaciclib plus pembrolizumab with/without anastrozole in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC) without prior CDK4 and 6 inhibitor exposure. Patients were divided into two cohorts: treatment naïve (cohort 1) and pretreated (cohort 2). Patients received abemaciclib plus pembrolizumab with (cohort 1) or without (cohort 2) anastrozole over 21-day cycles. The primary objective was safety, and secondary objectives included efficacy and pharmacokinetics (PK). Cohort 1/2 enrolled 26/28 patients, respectively. Neutropenia (30.8/28.6%), AST increase (34.6/17.9%), ALT increase (42.3/10.7%), and diarrhea (3.8/10.7%) were the most frequent grade ≥3 adverse events in cohort 1/2, respectively. A total of two deaths occurred, which investigators attributed to treatment-related adverse events (AEs), both in cohort 1. Higher rates of all grade and grade ≥3 interstitial lung disease (ILD)/pneumonitis were observed compared to previously reported with abemaciclib and pembrolizumab monotherapy. The PK profiles were consistent between cohorts and with previous monotherapy studies. In cohorts 1/2, the overall response rate and disease control rate were 23.1/28.6% and 84.6/82.1%, respectively. Median progression-free survival and overall survivals were 8.9 (95% CI: 3.9-11.1) and 26.3 months (95% CI: 20.0-31.0) for cohort 2; cohort 1 data are immature. Abemaciclib plus pembrolizumab demonstrated antitumor activity, but high rates of ILD/pneumonitis and severe transaminase elevations occurred with/without anastrozole compared to the previous reporting. Benefit/risk analysis does not support further evaluation of this combination in the treatment of HR+, HER2- MBC.

Disinfectant Activity of A Portable Ultraviolet C Equipment.

Healthcare-associated infections (HAIs) can be caused by microorganisms present in common practice instruments generating major health problems in the hospital environment. The aim of this work was to evaluate the disinfection capacity of a portable ultraviolet C equipment (UV Sanitizer Corvent® -UVSC-) developed to disinfect different objects. For this purpose, six pathogens causing HAIs: Acinetobacter baumannii, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans, were inoculated on slides and discs of different biomaterials (borosilicate, polycarbonate, polyurethane, silicone, Teflon and titanium) and exposed to ultraviolet C radiation. UVSC disinfection was compared with ethanol and chlorhexidine antimicrobial activities following the standards EN14561 and EN14562. Disinfection, established as a reduction of five logarithms from the initial inoculum, was achieved with the UVSC at 120 s of exposure time, with and without the presence of organic matter. The disinfectant effect was observed against S. aureus, P. aeruginosa, E. coli, B. subtilis and C. albicans (reduction >99.999%). Disinfection was also achieved with 70% ethanol and 2% chlorhexidine. As conclusion, UVSC was effective disinfecting the most contaminated surfaces assayed, being a promising alternative for disinfecting hospital materials and inanimate objects that cannot be immersed in liquid biocides, reducing the risk of pathogen transmission.

Phase III evaluating the addition of fulvestrant (F) to anastrozole (A) as adjuvant therapy in postmenopausal women with hormone receptor-positive HER2-negative (HR+/HER2-) early breast cancer (EBC): results from the GEICAM/2006-10 study.

PURPOSE: GEICAM/2006-10 compared anastrozole (A) versus fulvestrant plus anastrozole (A + F) to test the hypothesis of whether a complete oestrogen blockade is superior to aromatase inhibitors alone in breast cancer patients receiving hormone adjuvant therapy. METHODS: Multicenter, open label, phase III study. HR+/HER2- EBC postmenopausal patients were randomized 1:1 to adjuvant A (5 years [year]) or A + F (A plus F 250 mg/4 weeks for 3 year followed by 2 year of A). Stratification factors: prior chemotherapy (yes/no); number of positive lymph nodes (0/1-3/≥ 4); HR status (both positive/one positive) and site. PRIMARY OBJECTIVE: disease-free survival (DFS). Planned sample size: 2852 patients. RESULTS: The study has an early stop due to the financer decision with 870 patients (437 randomized to A and 433 to A + F). Patient characteristics were well balanced. After a median follow-up of 6.24y and 111 DFS events (62 in A and 49 in A + F) the Hazard Ratio for DFS (combination vs. anastrozole) was 0.84 (95% CI 0.58-1.22; p = 0.352). The proportion of patients disease-free in arms A and A + F at 5 year and 7 year were 90.8% versus 91% and 83.6% versus 86.7%, respectively. Most relevant G2-4 toxicities (≥ 5% in either arm) with A versus A + F were joint pain (14.7%; 13.7%), fatigue (2.5%; 7.2%), bone pain (3%; 6.5%), hot flushes (3.5%; 5%) and muscle pain (2.8%; 5.1%). CONCLUSIONS: The GEICAM/2006-10 study did not show a statistically significant increase in DFS by adding adjuvant F to A, though no firm conclusions can be drawn because of the limited sample size due to the early stop of the trial. ClinicalTrials.gov: NCT00543127.

Upper Tract Urothelial Carcinomas: Prognostic Factors and Outcomes in Patients With Non-Lymph Node Distant Metastasis.

BACKGROUND: Upper tract urothelial carcinomas (UTUCs) are increasingly recognized as separate malignancies. Additional insight into clinical outcomes and key prognostic factors are needed. OBJECTIVES: To detail outcomes of patients with UTUCs recurring after radical nephroureterectomy (RNU) and to determine a risk score that predicts outcomes of patients with non-lymph node distant metastasis. DESIGN, SETTING, AND PARTICIPANTS: Chart review of all patients who had an extraurothelial recurrence after RNU for UTUC at Dana-Farber Cancer Institute between 2009 and 2014. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Median overall survival defined as time from chemotherapy for distant relapse to death. Prognostic relevance of performance status, hemoglobin, and receipt of cisplatin were assessed by Cox regression model. RESULTS AND LIMITATIONS: A total of 102 patients were identified, 57 of whom had non-lymph node distant metastases at relapse; 45 received chemotherapy. Median follow-up was 29.8 months; median overall survival was 14.7 months. Objective response rate to any chemotherapy in the first-line setting was only 22%. Hemoglobin > 11 g/dL and receipt of cisplatin was associated with numerically longer median survival but did not reach statistical significance in univariate and multivariate analysis. Prognostic risk score scale including hemoglobin < 11 g/dL and receipt of cisplatin was inversely associated with survival, with scores of 0, 1, and 2 leading to median survival of 19.0, 14.9, and 7.2 months (P = .38), respectively. CONCLUSIONS: Advanced UTUC portends a poor prognosis, and most patients cannot receive cisplatin-based chemotherapy. A risk score that includes anemia and receipt of cisplatin helps stratify patients with distant metastasis for inclusion into eventual clinical trials. More studies are needed to validate these findings. PATIENT SUMMARY: Metastatic UTUC is an aggressive disease, where anemia and ineligibility to receive cisplatin are adverse features associated with shorter survival.

A nomogram for predicting complications in patients with solid tumours and seemingly stable febrile neutropenia.

BACKGROUND: We sought to develop and externally validate a nomogram and web-based calculator to individually predict the development of serious complications in seemingly stable adult patients with solid tumours and episodes of febrile neutropenia (FN). PATIENTS AND METHODS: The data from the FINITE study (n=1133) and University of Salamanca Hospital (USH) FN registry (n=296) were used to develop and validate this tool. The main eligibility criterion was the presence of apparent clinical stability, defined as events without acute organ dysfunction, abnormal vital signs, or major infections. Discriminatory ability was measured as the concordance index and stratification into risk groups. RESULTS: The rate of infection-related complications in the FINITE and USH series was 13.4% and 18.6%, respectively. The nomogram used the following covariates: Eastern Cooperative Group (ECOG) Performance Status ⩾2, chronic obstructive pulmonary disease, chronic cardiovascular disease, mucositis of grade ⩾2 (National Cancer Institute Common Toxicity Criteria), monocytes <200/mm(3), and stress-induced hyperglycaemia. The nomogram predictions appeared to be well calibrated in both data sets (Hosmer-Lemeshow test, P>0.1). The concordance index was 0.855 and 0.831 in each series. Risk group stratification revealed a significant distinction in the proportion of complications. With a ⩾116-point cutoff, the nomogram yielded the following prognostic indices in the USH registry validation series: 66% sensitivity, 83% specificity, 3.88 positive likelihood ratio, 48% positive predictive value, and 91% negative predictive value. CONCLUSIONS: We have developed and externally validated a nomogram and web calculator to predict serious complications that can potentially impact decision-making in patients with seemingly stable FN.

Prediction of serious complications in patients with seemingly stable febrile neutropenia: validation of the Clinical Index of Stable Febrile Neutropenia in a prospective cohort of patients from the FINITE study.

PURPOSE: To validate a prognostic score predicting major complications in patients with solid tumors and seemingly stable episodes of febrile neutropenia (FN). The definition of clinical stability implies the absence of organ dysfunction, abnormalities in vital signs, and major infections. PATIENTS AND METHODS: We developed the Clinical Index of Stable Febrile Neutropenia (CISNE), with six explanatory variables associated with serious complications: Eastern Cooperative Oncology Group performance status ≥ 2 (2 points), chronic obstructive pulmonary disease (1 point), chronic cardiovascular disease (1 point), mucositis of grade ≥ 2 (National Cancer Institute Common Toxicity Criteria; 1 point), monocytes < 200 per µL (1 point), and stress-induced hyperglycemia (2 points). We integrated these factors into a score ranging from 0 to 8, which classifies patients into three prognostic classes: low (0 points), intermediate (1 to 2 points), and high risk (≥ 3 points). We present a multicenter validation of CISNE. RESULTS: We prospectively recruited 1,133 patients with seemingly stable FN from 25 hospitals. Complication rates in the training and validation subsets, respectively, were 1.1% and 1.1% in low-, 6.1% and 6.2% in intermediate-, and 32.5% and 36% in high-risk patients; mortality rates within each class were 0% in low-, 1.6% and 0% in intermediate-, and 4.3% and 3.1% in high-risk patients. Areas under the receiver operating characteristic curves in the validation subset were 0.652 (95% CI, 0.598 to 0.703) for Talcott, 0.721 (95% CI, 0.669 to 0.768) for Multinational Association for Supportive Care in Cancer (MASCC), and 0.868 (95% CI, 0.827 to 0.903) for CISNE (P = .002 for comparison between CISNE and MASCC). CONCLUSION: CISNE is a valid model for accurately classifying patients with cancer with seemingly stable FN episodes.