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vrijdag 25 augustus 2017

The Lancet: [Comment] ACT IV: the final act for rindopepimut?

[Comment] ACT IV: the final act for rindopepimut?
Glioblastoma remains an almost universally fatal cancer with few recent therapeutic advances. The gene encoding EGFR is the most frequently amplified gene in glioblastoma, with roughly 40% of primary glioblastomas showing EGFR amplification.1 Of these EGFR-amplified glioblastomas, 20–50% are characterised by a truncated gene resulting in the expression of mutated EGFRvIII, which is constitutively active. Activation of the EGFR pathway promotes several downstream pathways with oncogenic potential such as cellular proliferation and invasiveness.
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[Comment] Carfilzomib versus bortezomib: no longer an ENDEAVOR
Carfilzomib is an irreversible, epoxyketone proteasome inhibitor, whereas bortezomib is a reversible, boronic acid-based proteasome inhibitor. The randomised phase 3 ENDEAVOR study directly compared carfilzomib (56 mg/m2) plus dexamethasone with bortezomib (1·3 mg/m2) plus dexamethasone in patients with relapsed or refractory multiple myeloma who had received between one and three previous therapies. The first pre-specified interim analysis showed that patients in the carfilzomib group had higher rates of deeper responses, which translated into significantly longer progression-free survival than those who received bortezomib (median progression-free survival 18·7 months [95% CI 15·6–not estimable] vs 9·4 months [8·4–10·4], hazard ratio [HR] 0·53 [95% CI 0·44–0·65]; p<0·0001).
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[Articles] Carfilzomib or bortezomib in relapsed or refractory multiple myeloma (ENDEAVOR): an interim overall survival analysis of an open-label, randomised, phase 3 trial
Carfilzomib provided a significant and clinically meaningful reduction in the risk of death compared with bortezomib. To our knowledge, carfilzomib is the first and only multiple myeloma treatment that extends overall survival in the relapsed setting over the current standard of care. This study is informative for deciding which proteasome inhibitor to use for treating this disease.
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[News] Labetuzumab govitecan in metastatic colorectal cancer
Labetuzumab govitecan monotherapy might be safe and effective in patients with relapsed or refractory metastatic colorectal cancer previously treated with irinotecan-containing therapy.
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[Articles] Guadecitabine (SGI-110) in treatment-naive patients with acute myeloid leukaemia: phase 2 results from a multicentre, randomised, phase 1/2 trial
More than half of older treatment-naive patients with acute myeloid leukaemia achieved a composite complete response with guadecitabine at all drug doses and schedules investigated, with tolerable toxicity. The recommended guadecitabine regimen for this population is 60 mg/m2 in a 5-day schedule. A phase 3 study in this patient population is ongoing (NCT02348489) to assess guadecitabine 60 mg/m2 in a 5-day schedule versus standard of care.
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