INTELLANCE 2/EORTC 1410 randomized phase II study of Depatux-M alone and with temozolomide vs temozolomide or lomustine in recurrent EGFR amplified glioblastoma

BACKGROUND: Depatuxizumab mafodotin (Depatux-M) is a tumor-specific antibody-drug conjugate consisting of an antibody (ABT-806) directed against activated epidermal growth factor receptor (EGFR) and the toxin monomethylauristatin-F. We investigated Depatux-M in combination with temozolomide or as a single agent in a randomized controlled phase II trial in recurrent EGFR amplified glioblastoma. METHODS: Eligible were patients with centrally confirmed EGFR amplified glioblastoma at first recurrence after chemo-irradiation with temozolomide. Patients were randomized to either Depatux-M 1.25 mg/kg every 2 weeks intravenously, or this treatment combined with temozolomide 150-200 mg/m2 day 1-5 every 4 weeks, or either lomustine or temozolomide. The primary endpoint of the study was overall survival. RESULTS: Two hundred sixty patients were randomized. In the primary efficacy analysis with 199 events (median follow-up 15.0 mo), the hazard ratio (HR) for the combination arm compared with the control arm was 0.71 (95% CI = 0.50, 1.02; P = 0.062). The efficacy of Depatux-M monotherapy was comparable to that of the control arm (HR = 1.04, 95% CI = 0.73, 1.48; P = 0.83). The most frequent toxicity in Depatux-M treated patients was a reversible corneal epitheliopathy, occurring as grades 3-4 adverse events in 25-30% of patients. In the long-term follow-up analysis with median follow-up of 28.7 months, the HR for the comparison of the combination arm versus the control arm was 0.66 (95% CI = 0.48, 0.93). CONCLUSION: This trial suggests a possible role for the use of Depatux-M in combination with temozolomide in EGFR amplified recurrent glioblastoma, especially in patients relapsing well after the end of first-line adjuvant temozolomide treatment. (NCT02343406)

Erratum: INTELLANCE 2/EORTC 1410 randomized phase II study of Depatux-M alone and with temozolomide vs temozolomide or lomustine in recurrent EGFR amplified glioblastoma (Neuro-Oncology DOI: 10.1093/neuonc/noz222)

Corrigendum to Bent et al. INTELLANCE 2/EORTC 1410 randomized phase II study of Depatux-M alone and with temozolomide vs temozolomide or lomustine in recurrent EGFR amplified glioblastoma. Neuro Oncol (doi: 10.1093/neuonc/noz222) first published online November 20, 2019. In table 2, the rows in the hematology and investigation sections were misplaced one line. This has been corrected

INTELLANCE 2/EORTC 1410 randomized phase II study of Depatux-M alone and with temozolomide vs temozolomide or lomustine in recurrent EGFRamplified glioblastoma.

BACKGROUND Depatux-M is a tumor-specific antibody-drug-conjugate consisting of an antibody (ABT-806) directed against the activated Epithelial Growth Factor Receptor (EGFR) and the toxin monomethylauristatin-F. We investigated Depatux-M in combination with temozolomide or as single agent in a randomized controlled phase II trial in recurrent EGFR amplified glioblastoma. PATIENTS AND METHODS Eligible were patients with centrally confirmed EGFR amplified glioblastoma at first recurrence after chemo-irradiation with temozolomide. Patients were randomized to either Depatux-M 1.25 mg/kg every 2 weeks intravenously, or this treatment combined with temozolomide 150-200 mg/m2 day 1-5 every 4 weeks, or either lomustine or temozolomide. The primary endpoint of the study was overall survival. RESULTS 260 patients were randomized. In the primary efficacy analysis with 199 events (median follow-up 15.0 months) the hazard ratio (HR) for the combination arm compared to the control arm was 0.71, 95% CI [0.50, 1.02]; p = 0.062. The efficacy of Depatux-M monotherapy was comparable to that of the control arm (HR =1.04, 95%CI [0.73, 1.48]; p = 0.83). The most frequent toxicity in Depatux-M treated patients was a reversible corneal epitheliopathy, occurring as grade 3-4 in 25-30% of patients. In the long-term follow-up analysis with median follow-up of 28,7 months the HR for the comparison of the combination arm versus the control arm was 0.66 (95%CI [0.48, 0.93]. CONCLUSION This trial suggests a possible role for the use of Depatux-M in combination with temozolomide in EGFR amplified recurrent glioblastoma, especially in patients relapsing well after the end of first-line adjuvant temozolomide treatment. (NCT02343406)

Konkurenční analýza stavebního spoření

Seznámení s problematikou stavebního spoření a jeho využití při řešení bytové situace. Porovnání současných podmínek s podmínkami platnými do 31.12.2003. Zhodnocení dané problematiky u jednotlivých staveních spořitelen. Zhodnocení SS do budoucna a jeho dopady do státního rozpočtu

Species distribution modelling: contrasting presence-only models with plot abundance data

Species distribution models (SDMs) are widely used in ecology and conservation. Presence-only SDMs such as MaxEnt frequently use natural history collections (NHCs) as occurrence data, given their huge numbers and accessibility. NHCs are often spatially biased which may generate inaccuracies in SDMs. Here, we test how the distribution of NHCs and MaxEnt predictions relates to a spatial abundance model, based on a large plot dataset for Amazonian tree species, using inverse distance weighting (IDW). We also propose a new pipeline to deal with inconsistencies in NHCs and to limit the area of occupancy of the species. We found a significant but weak positive relationship between the distribution of NHCs and IDW for 66% of the species. The relationship between SDMs and IDW was also significant but weakly positive for 95% of the species, and sensitivity for both analyses was high. Furthermore, the pipeline removed half of the NHCs records. Presence-only SDM applications should consider this limitation, especially for large biodiversity assessments projects, when they are automatically generated without subsequent checking. Our pipeline provides a conservative estimate of a species’ area of occupancy, within an area slightly larger than its extent of occurrence, compatible to e.g. IUCN red list assessments