Final Results of Urelumab, an Anti-CD137 Agonist Monoclonal Antibody, in Combination With Cetuximab or Nivolumab in Patients With Advanced Solid Tumors

BACKGROUND: Resistance to immune checkpoint inhibitors and targeted treatments for cancer is common; thus, novel immunotherapy agents are needed. Urelumab is a monoclonal antibody agonist that binds to CD137 receptors expressed on T cells. Here, we report two studies that evaluated urelumab in combination with cetuximab or nivolumab in patients with select, advanced solid tumors. METHODS: CA186-018: Patients with metastatic colorectal cancer or metastatic squamous cell carcinoma of the head and neck (SCCHN) were treated in a dose-evaluation phase with urelumab 0.1 mg/kg (urelumab-0.1) every 3 weeks (Q3W)+cetuximab 250 mg/m RESULTS: CA186-018: 66 patients received study treatment. The most frequent treatment-related adverse events (TRAEs) were fatigue (75%; n=3) with urelumab-0.1+cetuximab-250 and dermatitis (45%; n=28) with urelumab-8+cetuximab-250. Three patients (5%) discontinued due to TRAE(s) (with urelumab-8+cetuximab-250). One patient with SCCHN had a partial response (objective response rate (ORR) 5%, with urelumab-8+cetuximab-250).CA186-107: 134 patients received study treatment. Fatigue was the most common TRAE (32%; n=2 with urelumab-3+nivolumab-3; n=1 with urelumab-8+nivolumab-3; n=40 with urelumab-8+nivolumab-240). Nine patients (7%) discontinued due to TRAE(s) (n=1 with urelumab-3+nivolumab-3; n=8 with urelumab-8+nivolumab-240). Patients with melanoma naive to anti-PD-1 therapy exhibited the highest ORR (49%; n=21 with urelumab-8+nivolumab-240). Intratumoral gene expression in immune-related pathways (CD3, CD8, CXCL9, GZMB) increased on treatment with urelumab+nivolumab. CONCLUSIONS: Although the addition of urelumab at these doses was tolerable, preliminary response rates did not indicate an evident additive benefit. Nevertheless, the positive pharmacodynamics effects observed with urelumab and the high response rate in treatment-naive patients with melanoma warrant further investigation of other anti-CD137 agonist agents for treatment of cancer

Data from: Postpartum family planning integration with maternal, newborn, and child health services: a cross-sectional analysis of client flow patterns in India and Kenya

Objectives: Maternal, newborn, and child health (MNCH) services represent opportunities to integrate postpartum family planning (PPFP). Objectives were to determine levels of MNCH-family planning (FP) integration and associations between integration, client characteristics, and service delivery factors in facilities that received programmatic PPFP support. Design and setting: Cross-sectional client flow assessment conducted May–July 2014, over 5 days at 10 purposively selected public sector facilities in India (four hospitals) and Kenya (two hospitals, four health centers). Participants: 2,158 client visits tracked (1,294 India; 864 Kenya). Women aged 18 or older accessing services while pregnant and/or with a child under 2 years. Interventions: PPFP/postpartum intrauterine device—Bihar, India (2012–2013); Jharkhand, India (2010–2014); Embu, Kenya (2008–2012). Maternal, infant, and young child nutrition/FP integration—Bondo, Kenya (2011–2013). Primary outcome measures: Proportion of visits where clients received integrated MNCH-FP services, client characteristics as predictors of MNCH-FP integration, and MNCH-FP integration as predictor of length of time spent at facility. Results: Levels of MNCH-FP integration varied widely across facilities (5.3% to 63.0%), as did proportion of clients receiving MNCH-FP integrated services by service area. Clients traveling 30–59 minutes were half as likely to receive integrated services versus those traveling under 30 minutes (odds ratio [OR] 0.5, 95% confidence interval [CI] 0.4–0.7, p<.001). Clients receiving MNCH-FP services (versus MNCH services only) spent an average of 10.5 minutes longer at the facility (95% CI −0.1–21.9, not statistically significant). Conclusions: Findings suggest importance of focused programmatic support for integration by MNCH service area. FP integration was highest in areas receiving specific support. Integration does not seem to impose an undue burden on clients in terms of time spent at the facility. Clients living furthest from facilities are least likely to receive integrated services

Client Flow Base Dataset 10 Oct 2014 (Stata) (De-Identified)

Base dataset for client flow data collected under the study "A Descriptive Evaluation of Postpartum Family Planning Integration Models in Kenya and India," conducted in 2014 by the Maternal and Child Survival Program. Stata version

Client Flow Base Dataset 10 Oct 2014 (SPSS) (De-Identified)

Base dataset for client flow data collected under the study "A Descriptive Evaluation of Postpartum Family Planning Integration Models in Kenya and India," conducted in 2014 by the Maternal and Child Survival Program. SPSS version

Client Flow Dataset BASE 2014.10.10 (CSV) (De-Identified)

Base dataset for client flow data collected under the study "A Descriptive Evaluation of Postpartum Family Planning Integration Models in Kenya and India," conducted in 2014 by the Maternal and Child Survival Program. CSV format

Client Flow Codebook

Codebook for the client flow dataset collected under the study "A Descriptive Evaluation of Postpartum Family Planning Integration Models in Kenya and India," conducted in 2014 by the Maternal and Child Survival Program

Serotype-specific changes in invasive pneumococcal disease after pneumococcal conjugate vaccine introduction: a pooled analysis of multiple surveillance sites

BACKGROUND: Vaccine-serotype (VT) invasive pneumococcal disease (IPD) rates declined substantially following introduction of 7-valent pneumococcal conjugate vaccine (PCV7) into national immunization programs. Increases in non-vaccine-serotype (NVT) IPD rates occurred in some sites, presumably representing serotype replacement. We used a standardized approach to describe serotype-specific IPD changes among multiple sites after PCV7 introduction. METHODS AND FINDINGS: Of 32 IPD surveillance datasets received, we identified 21 eligible databases with rate data ≥ 2 years before and ≥ 1 year after PCV7 introduction. Expected annual rates of IPD absent PCV7 introduction were estimated by extrapolation using either Poisson regression modeling of pre-PCV7 rates or averaging pre-PCV7 rates. To estimate whether changes in rates had occurred following PCV7 introduction, we calculated site specific rate ratios by dividing observed by expected IPD rates for each post-PCV7 year. We calculated summary rate ratios (RRs) using random effects meta-analysis. For children <5 years old, overall IPD decreased by year 1 post-PCV7 (RR 0.55, 95% CI 0.46-0.65) and remained relatively stable through year 7 (RR 0.49, 95% CI 0.35-0.68). Point estimates for VT IPD decreased annually through year 7 (RR 0.03, 95% CI 0.01-0.10), while NVT IPD increased (year 7 RR 2.81, 95% CI 2.12-3.71). Among adults, decreases in overall IPD also occurred but were smaller and more variable by site than among children. At year 7 after introduction, significant reductions were observed (18-49 year-olds [RR 0.52, 95% CI 0.29-0.91], 50-64 year-olds [RR 0.84, 95% CI 0.77-0.93], and ≥ 65 year-olds [RR 0.74, 95% CI 0.58-0.95]). CONCLUSIONS: Consistent and significant decreases in both overall and VT IPD in children occurred quickly and were sustained for 7 years after PCV7 introduction, supporting use of PCVs. Increases in NVT IPD occurred in most sites, with variable magnitude. These findings may not represent the experience in low-income countries or the effects after introduction of higher valency PCVs. High-quality, population-based surveillance of serotype-specific IPD rates is needed to monitor vaccine impact as more countries, including low-income countries, introduce PCVs and as higher valency PCVs are used. Please see later in the article for the Editors' Summary