Annals of oncology : official journal of the European Society for Medical Oncology
-
Clinical Trial
Osimertinib benefit in EGFR-mutant NSCLC patients with T790M-mutation detected by circulating tumour DNA.
Approximately 50% of epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitors (TKIs) will acquire resistance by the T790M mutation. Osimertinib is the standard of care in this situation. The present study assesses the efficacy of osimertinib when T790M status is determined in circulating cell-free tumour DNA (ctDNA) from blood samples in progressing advanced EGFR-mutant NSCLC patients. ⋯ ctDNA from liquid biopsy can be used as a surrogate marker for T790M in tumour tissue.
-
Anaplastic lymphoma kinase (ALK) inhibition using crizotinib has become the standard of care in advanced ALK-rearranged non-small cell lung cancer (NSCLC), but the treatment outcomes and duration of response vary widely. Echinoderm microtubule-associated protein-like 4 (EML4)-ALK is the most common translocation, and the fusion variants show different sensitivity to crizotinib in vitro. However, there are only limited data on the specific EML4-ALK variants and clinical responses of patients to various ALK inhibitors. ⋯ Our findings show that group EML4-ALK variants 3a/b may be a major source of ALK inhibitor resistance in the clinic. The variant-specific genotype of the EML4-ALK fusion allows for more precise stratification of patients with advanced NSCLC.
-
Randomized Controlled Trial
Pembrolizumab as first-line therapy for patients with PD-L1-positive advanced non-small cell lung cancer: a phase 1 trial.
Pembrolizumab improved survival as first- and second-line therapy compared with chemotherapy in patients with highly programmed death ligand 1 (PD-L1) expressing advanced non-small cell lung cancer (NSCLC). We report the long-term safety and clinical activity of pembrolizumab as first-line therapy for patients with advanced NSCLC and the correlation between PD-L1 expression and efficacy. ⋯ KEYNOTE-001 (ClinicalTrials.gov, NCT01295827).
-
Randomized Controlled Trial
Cabozantinib in hepatocellular carcinoma: results of a phase 2 placebo-controlled randomized discontinuation study.
Cabozantinib, an orally bioavailable inhibitor of tyrosine kinases including MET, AXL, and VEGF receptors, was assessed in patients with hepatocellular carcinoma (HCC) as part of a phase 2 randomized discontinuation trial with nine tumor-type cohorts. ⋯ Cabozantinib has clinical activity in HCC patients, including objective tumor responses, disease stabilization, and reductions in AFP. Adverse events were managed with dose reductions.
-
Multicenter Study Clinical Trial
Multimodality treatment for esophageal adenocarcinoma: multi-center propensity-score matched study.
The primary aim of this study was to compare survival from neoadjuvant chemoradiotherapy plus surgery (NCRS) versus neoadjuvant chemotherapy plus surgery (NCS) for the treatment of esophageal or junctional adenocarcinoma. The secondary aims were to compare pathological effects, short-term mortality and morbidity, and to evaluate the effect of lymph node harvest upon survival in both treatment groups. ⋯ The survival differences between NCRS and NCS maybe modest, if present at all, for the treatment of locally advanced esophageal or junctional adenocarcinoma. Future large-scale randomized trials must control and monitor indicators of the quality of surgery, as the extent of lymphadenectomy appears to influence prognosis in patients treated with NCS, from this large multi-center European study.