Cancer discovery
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Larotrectinib, a selective TRK tyrosine kinase inhibitor (TKI), has demonstrated histology-agnostic efficacy in patients with TRK fusion-positive cancers. Although responses to TRK inhibition can be dramatic and durable, duration of response may eventually be limited by acquired resistance. LOXO-195 is a selective TRK TKI designed to overcome acquired resistance mediated by recurrent kinase domain (solvent front and xDFG) mutations identified in multiple patients who have developed resistance to TRK TKIs. ⋯ This establishes a role for sequential treatment by demonstrating continued TRK dependence and validates a paradigm for the accelerated development of next-generation inhibitors against validated oncogenic targets. Cancer Discov; 7(9); 963-72. ©2017 AACR. See related commentary by Parikh and Corcoran, p. 934This article is highlighted in the In This Issue feature, p. 920.
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The first clinical trial of the investigational drug enasidenib, which targets IDH2 mutations, suggests that it is safe and may improve survival in patients with relapsed or refractory acute myeloid leukemia. It induced responses in 40.3% of patients, yielding a median overall survival of 9.3 months.
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Disruption of the programmed cell death protein 1 (PD-1) pathway with immune checkpoint inhibitors represents a major breakthrough in the treatment of non-small cell lung cancer. We hypothesized that combined inhibition of C5a/C5aR1 and PD-1 signaling may have a synergistic antitumor effect. The RMP1-14 antibody was used to block PD-1, and an L-aptamer was used to inhibit signaling of complement C5a with its receptors. ⋯ This study provides the preclinical rationale for the combined blockade of PD-1/PD-L1 and C5a to restore antitumor immune responses, inhibit tumor cell growth, and improve outcomes of patients with lung cancer. Cancer Discov; 7(7); 694-703. ©2017 AACR. This article is highlighted in the In This Issue feature, p. 653.
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Based on results of the phase III BILCAP study, adjuvant capecitabine should become standard treatment for patients with biliary tract cancer. Among 430 patients who were treated according to the study protocol, capecitabine was associated with a 25% lower risk of death than observation.
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The FDA recently expanded label indications for regorafenib to include treating patients with advanced hepatocellular carcinoma whose disease has progressed on the standard of care, sorafenib. Until now, these patients have had no other treatment options. Regorafenib is the first drug to be approved for liver cancer in a decade.