Final Results for Adjuvant Dabrafenib plus Trametinib in Stage III Melanoma.

BACKGROUND: The 5-year results of this trial showed that adjuvant therapy with dabrafenib plus trametinib resulted in longer relapse-free survival and distant metastasis-free survival than placebo among patients with BRAF V600-mutated stage III melanoma. Longer-term data were needed, including data regarding overall survival. METHODS: We randomly assigned 870 patients with resected stage III melanoma with BRAF V600 mutations to receive 12 months of dabrafenib (150 mg twice daily) plus trametinib (2 mg once daily) or two matched placebos. Here, we report the final results of this trial, including results for overall survival, melanoma-specific survival, relapse-free survival, and distant metastasis-free survival. RESULTS: The median duration of follow-up was 8.33 years for dabrafenib plus trametinib and 6.87 years for placebo. Kaplan-Meier estimates for overall survival favored dabrafenib plus trametinib over placebo, although the benefit was not significant (hazard ratio for death, 0.80; 95% confidence interval [CI], 0.62 to 1.01; P = 0.06 by stratified log-rank test). A consistent survival benefit was seen across several prespecified subgroups, including the 792 patients with melanoma with a BRAF V600E mutation (hazard ratio for death, 0.75; 95% CI, 0.58 to 0.96). Relapse-free survival favored dabrafenib plus trametinib over placebo (hazard ratio for relapse or death, 0.52; 95% CI, 0.43 to 0.63), as did distant metastasis-free survival (hazard ratio for distant metastasis or death, 0.56; 95% CI, 0.44 to 0.71). No new safety signals were reported, a finding consistent with previous trial reports. CONCLUSIONS: After nearly 10 years of follow-up, adjuvant therapy with dabrafenib plus trametinib was associated with better relapse-free survival and distant metastasis-free survival than placebo among patients with resected stage III melanoma. The analysis of overall survival showed that the risk of death was 20% lower with combination therapy than with placebo, but the benefit was not significant. Among patients with melanoma with a BRAF V600E mutation, the results suggest that the risk of death was 25% lower with combination therapy. (Funded by GlaxoSmithKline and Novartis; COMBI-AD ClinicalTrials.gov number, NCT01682083; EudraCT number, 2012-001266-15.).

WHO guidance for digital health: What it means for researchers.

In healthcare, digital solutions have been adopted with zeal, but there is paucity of evidence for benefits and harms of these solutions. The impact, immediate or long term, of digital applications on healthcare has not been assessed. With the overwhelming numbers and types of digital solutions, it is becoming increasingly important to develop evidence-based insights for the integration of these solutions in routine medical care. Digitalization can certainly empower and enable patients and physicians to achieve health objectives. The World Health Organisation has released guidance for digital health after a critical review of available evidence for the benefits, harms, acceptability, feasibility, resource use and equity considerations of digital health interventions. This guidance can potentially inspire and impact future research endeavors for digital applications. In this paper, the guidance has been reviewed in context of the current research situation and insights are shared for researchers engaged in the design and assessment of digital interventions.

Tobacco control in India: present scenario and challenges ahead.

Tobacco imposes a colossal burden of disease and death leading to catastrophic health, social, economic and environmental effects. Prevalence and practices of tobacco use in India are varied and disparate. Tobacco consumption continues to grow at 2-3% per annum, and by 2020 it is predicted that it will account for 13% of all deaths in the country. India is now demonstrating a steely resolve to contain the menace of tobacco through a comprehensive control strategy that combines several demand and supply reduction measures. India's anti-tobacco legislation, first passed at the national level in 1975, was largely limited to health warnings and proved to be inefficient. The 'Cigarettes and Other Tobacco Products Bill, 2003' represented an advance in tobacco control. It included demand reduction measures like outlawing smoking in public places, forbidding sale of tobacco to minors, requiring more prominent health warning labels, and banning advertising at sports and cultural events. India, as a signatory to FCTC, is actively involved in combating the menace of tobacco with renewed fervor. There is a need to devise innovative methods of mobilizing financial and human resources for tobacco control, establish efficient national coordinating mechanisms, integrate tobacco control into health and development programs and periodically evaluate these activities. The Government must also introduce policies to raise taxes, control smuggling, close advertising loopholes, and create adequate provisions for the enforcement of tobacco control laws.