ABSTRACT
BACKGROUND: Time to next treatment or death (TNT-D) may be a patient-relevant endpoint in patients treated with immune checkpoint inhibitors. This study investigated TNT-D as a surrogate endpoint (SE) for overall survival (OS) in previously untreated advanced melanoma patients. METHODS: Patient-level data from the 60-month results of the CheckMate 067 randomised, controlled trial were used. Analyses were carried out for nivolumab monotherapy or nivolumab with ipilimumab versus ipilimumab monotherapy. The SE 1-step validation method based on a joint frailty-copula model was used where the country of enrolment was applied to define clusters. Kendall's τ and the coefficient of determination (R2trial) were estimated for respective measurements of association at the individual and cluster levels. The surrogate threshold effect, the maximum threshold hazard ratio for TNT-D that would translate into OS benefit, was estimated. A leave-one-out cross-validation analysis was carried out to evaluate model robustness. RESULTS: Fifteen clusters of data were generated from 945 patients. For both nivolumab-containing arms, the association between TNT-D and OS was deemed acceptable at the individual level (Kendall's τ > 0.60) and strong at the cluster level, with R2trial fairly close to 1, with narrow confidence intervals. The estimated surrogate threshold effects were 0.61 for nivolumab versus ipilimumab and 0.49 for nivolimub + ipilimumab versus ipilimumab. Cross-validation results showed minimum variation of the correlation measures and satisfactory predictive accuracy for the model. CONCLUSION: Results suggest that TNT-D may be a valuable SE in previously untreated advanced melanoma patients treated with immune checkpoint inhibitors. Surrogacy analyses considering multiple randomised controlled trials are warranted for confirming these findings.
Subject(s)
Immune Checkpoint Inhibitors , Melanoma , Antineoplastic Combined Chemotherapy Protocols , Biomarkers , Clinical Trials, Phase III as Topic , Humans , Ipilimumab/pharmacology , Ipilimumab/therapeutic use , Melanoma/drug therapyABSTRACT
BACKGROUND: In Cameroon in 2012, the proportion (15%) of children eligible for antiretroviral treatment (ART) was one of the lowest among the 21 Global Fund priority countries. The objective of this study was to carry out a situational analysis of the existing care offer for pediatric HIV in Cameroon. METHODS: A descriptive cross-sectional study was conducted over a 4-month period (April to August 2014) in 12 healthcare facilities in 7 regions of Cameroon selected by systematic sampling. The data were collected in a self-administered questionnaire filled out by the caregiving and administrative personnel included in the study. RESULTS: All in all, 142 persons in charge of pediatric HIV treatment were included in the study, of whom 115 were working at the operational level: 59 (51.2%) health personnel, 44 (38.3%) community agents and 12 (10.4%) department heads; the other 27 exercised responsibilities at the regional (19) and the local (8) levels. An overwhelming majority of the caregivers involved in pediatric VIH treatment were nurses, a factor necessitating the delegation of medical tasks institutionalized in Cameroon. Few standardized nationwide documents take into account these treatment modalities. Inadequate dissemination of the documents at all levels of the healthcare pyramid may justify the non-compliance with the care protocols that has been observed in the training programs dedicated to the subject. CONCLUSION: The updating and large-scale dissemination of standardized nationwide documents taking into account the specificities of HIV-infected children are required to improve implementation at the operational level of the Cameroonian healthcare system of the existing guidelines for pediatric HIV treatment.
