Operational Coverage and Timeliness of Reactive Case Detection for Malaria Elimination in Zanzibar, Tanzania.

Since 2012, the Zanzibar Malaria Elimination Program has been implementing reactive case detection (RACD). Health facility (HF) staff send individual malaria case notifications by using mobile phones, triggering a review of HF records and malaria testing and treatment at the household level by a district malaria surveillance officer. We assessed the completeness and timeliness of this system, from case notification to household-level response. We reviewed two years (2015-2016) of primary register information in 40 randomly selected HFs on Zanzibar's two islands Unguja and Pemba and database records of case notifications from all registered HFs for the period 2013-16. The operational coverage of the system was calculated as proportion of HF-registered cases that were successfully reviewed and followed up at their household. Timeliness was defined as completion of each step within 1 day. Public HFs notified almost all registered cases (91% in Unguja and 87% in Pemba), and 74% of cases registered at public HFs were successfully followed up at their household in Unguja and 79% in Pemba. Timely operational coverage (defined as each step, diagnosis to notification, notification to review, and review to household-level response, completed within 1 day) was achieved for only 25% of registered cases in Unguja and 30% in Pemba. Records and data from private HFs on Unguja indicated poor notification performance in the private sector. Although the RACD system in Zanzibar achieved high operational coverage, timeliness was suboptimal. Patients diagnosed with malaria at private HFs and hospitals appeared to be largely missed by the RACD system.

Challenges and Opportunities for Cancer Predisposition Cascade Screening for Hereditary Breast and Ovarian Cancer and Lynch Syndrome in Switzerland: Findings from an International Workshop.

BACKGROUND: An international workshop on cancer predisposition cascade genetic screening for hereditary breast and ovarian cancer (HBOC) and Lynch syndrome (LS) took place in Switzerland, with leading researchers and clinicians in cascade screening and hereditary cancer from different disciplines. The purpose of the workshop was to enhance the implementation of cascade genetic screening in Switzerland. Participants discussed the challenges and opportunities associated with cascade screening for HBOC and LS in Switzerland (CASCADE study); family implications and the need for family-based interventions; the need to evaluate the cost-effectiveness of cascade genetic screening; and interprofessional collaboration needed to lead this initiative. METHODS: The workshop aims were achieved through exchange of data and experiences from successful cascade screening programs in the Netherlands, Australia, and the state of Ohio, USA; Swiss-based studies and scientific experience that support cancer cascade screening in Switzerland; programs of research in psychosocial oncology and family-based studies; data from previous cost-effectiveness analyses of cascade genetic screening in the Netherlands and in Australia; and organizational experience from a large interprofessional collaborative. Scientific presentations were recorded and discussions were synthesized to present the workshop findings. RESULTS: The key elements of successful implementation of cascade genetic screening are a supportive network of stakeholders and connection to complementary initiatives; sample size and recruitment of relatives; centralized organization of services; data-based cost-effectiveness analyses; transparent organization of the initiative; and continuous funding. CONCLUSIONS: This paper describes the processes and key findings of an international workshop on cancer predisposition cascade screening, which will guide the CASCADE study in Switzerland.

Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): an international randomised, open-label, adaptive, phase 2/3 study.

BACKGROUND: Although trastuzumab plus chemotherapy is the standard of care for first-line treatment of HER2-positive advanced gastric cancer, there is no established therapy in the second-line setting. In GATSBY, we examined the efficacy and tolerability of trastuzumab emtansine in patients previously treated for HER2-positive advanced gastric cancer (unresectable, locally advanced, or metastatic gastric cancer, including adenocarcinoma of the gastro-oesophageal junction). METHODS: This is the final analysis from GATSBY, a randomised, open-label, adaptive, phase 2/3 study, done at 107 centres (28 countries worldwide). Eligible patients had HER2-positive advanced gastric cancer and progressed during or after first-line therapy. In stage one of the trial, patients were randomly assigned to treatment groups (2:2:1) to receive intravenous trastuzumab emtansine (3·6 mg/kg every 3 weeks or 2·4 mg/kg weekly) or physician's choice of a taxane (intravenous docetaxel 75 mg/m2 every 3 weeks or intravenous paclitaxel 80 mg/m2 weekly). In stage two, patients were randomly assigned to treatment groups (2:1) to receive the independent data monitoring committee (IDMC)-selected dose of trastuzumab emtansine (2·4 mg/kg weekly) or a taxane (same regimen as above). We used permuted block randomisation, stratified by world region, previous HER2-targeted therapy, and previous gastrectomy. The primary endpoint (overall survival) was assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01641939. FINDINGS: Between Sept 3, 2012, and Oct 14, 2013, 70 patients were assigned to receive trastuzumab emtansine 3·6 mg/kg every 3 weeks, 75 to receive trastuzumab emtansine 2·4 mg/kg weekly, and 37 to receive a taxane in the stage 1 part of the trial. At the pre-planned interim analysis (Oct 14, 2013), the IDMC selected trastuzumab emtansine 2·4 mg/kg weekly as the dose to proceed to stage 2. By Feb 9, 2015, a further 153 patients had been randomly assigned to receive trastuzumab emtansine 2·4 mg/kg weekly and a further 80 to receive a taxane. At data cutoff, median follow-up was 17·5 months (IQR 12·1-23·0) for the trastuzumab emtansine 2·4 mg/kg weekly group and 15·4 months (9·2-18·1) in the taxane group. Median overall survival was 7·9 months (95% CI 6·7-9·5) with trastuzumab emtansine 2·4 mg/kg weekly and 8·6 months (7·1-11·2) with taxane treatment (hazard ratio 1·15, 95% CI 0·87-1·51, one-sided p=0·86). The trastuzumab emtansine 2·4 mg/kg group had lower incidences of grade 3 or more adverse events (134 [60%] of 224 patients treated with trastuzumab emtansine vs 78 [70%] of 111 patients treated with a taxane), and similar incidences of adverse events leading to death (eight [4%] vs four [4%]), serious adverse events (65 [29%] vs 31 [28%]), and adverse events leading to treatment discontinuation (31 [14%] vs 15 [14%]) than did taxane treatment. The most common grade 3 or more adverse events in the trastuzumab emtansine 2·4 mg/kg weekly group were anaemia (59 [26%]) and thrombocytopenia (25 [11%]) compared with neutropenia (43 [39%]), and anaemia (20 [18%]), in the taxane group. The most common serious adverse events were anaemia (eight [4%]), upper gastrointestinal haemorrhage (eight [4%]), pneumonia (seven [3%]), gastric haemorrhage (six [3%]), and gastrointestinal haemorrhage (five [2%]) in the trastuzumab emtansine 2·4 mg/kg weekly group compared with pneumonia (four [4%]), febrile neutropenia (four [4%]), anaemia (three [3%]), and neutropenia (three [3%]) in the taxane group. INTERPRETATION: Trastuzumab emtansine was not superior to taxane in patients with previously treated, HER2-positive advanced gastric cancer. There is still an unmet need in this patient group and therapeutic options remain limited. FUNDING: F Hoffmann-La Roche.