The lancet oncology
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The lancet oncology · Jul 2020
Randomized Controlled Trial Multicenter StudyRipretinib in patients with advanced gastrointestinal stromal tumours (INVICTUS): a double-blind, randomised, placebo-controlled, phase 3 trial.
Resistance to approved inhibitors of KIT proto-oncogene, receptor tyrosine kinase (KIT), and platelet-derived growth factor receptor α (PDGFRA) is a clinical challenge for patients with advanced gastrointestinal stromal tumours. We compared the efficacy and safety of ripretinib, a switch-control tyrosine kinase inhibitor active against a broad spectrum of KIT and PDGFRA mutations, with placebo in patients with previously treated, advanced gastrointestinal stromal tumours. ⋯ Deciphera Pharmaceuticals.
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The lancet oncology · Jul 2020
Randomized Controlled Trial Multicenter StudyBerzosertib plus gemcitabine versus gemcitabine alone in platinum-resistant high-grade serous ovarian cancer: a multicentre, open-label, randomised, phase 2 trial.
High-grade serous ovarian cancers show increased replication stress, rendering cells vulnerable to ATR inhibition because of near universal loss of the G1/S checkpoint (through deleterious TP53 mutations), premature S phase entry (due to CCNE1 amplification, RB1 loss, or CDKN2A mRNA downregulation), alterations of homologous recombination repair genes, and expression of oncogenic drivers (through MYC amplification and other mechanisms). We hypothesised that the combination of the selective ATR inhibitor, berzosertib, and gemcitabine could show acceptable toxicity and superior efficacy to gemcitabine alone in high-grade serous ovarian cancer. ⋯ US National Cancer Institute.