DOI [Teaser] Key Summary Points While vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) are an essential therapeutic option in various solid tumors, post-marketing data regarding their potential cardiovascular toxicities are scant.

Updated findings from the ARROW trial show that pralsetinib has “robust efficacy” for the first-line treatment of locally advanced or metastatic, RET fusion-positive, non-small-cell lung cancer, the investigators say.

High tumor mutational burden is associated with a better response to immune checkpoint inhibitors in people with non-small-cell lung cancer across all levels of PD-L1 expression, US researchers report.

By that, I mean that an adenocarcinoma will switch to a small-cell carcinoma, and this will be the default mechanism of resistance to tyrosine kinase inhibitors.

Stephen Liu outlines the ARROW study design and findings and discusses the impact of pralsetinib on the care of patients with treatment-naïve and previously treated NSCLC positive for a RET fusion (7:20).

GEMSTONE-302: Sugemalimab plus chemotherapy for stage IV NSCLC This double-blind, phase 3 study was also conducted in China and enrolled 479 individuals with treatment-naïve, stage IV squamous or nonsquamous NSCLC without known EGFR sensitizing mutations, or ALK , ROS1 , or RET fusions.

Stephen Liu talks through the latest findings from the ARROW trial of pralsetinib for patients with RET fusion-positive advanced non-small-cell lung cancer.

medwireNews: The EMA has recommended granting a conditional marketing authorization to pralsetinib for use in patients with RET fusion-positive non-small-cell lung cancer (NSCLC) who are RET inhibitor-naïve.

medwireNews : The US FDA has approved selpercatinib  for the treatment of advanced lung and thyroid cancers with RET alterations.

A report of two patients with advanced tumors harboring alterations in the RET gene who responded to treatment with the selective inhibitor LOXO-292 highlights that the clinical actionability of RET mutations, say researchers.

A selective inhibitor of the receptor tyrosine kinase RET could benefit patients with tumors harboring alterations in the oncogene, suggest early results presented at the American Association for Cancer Research Annual Meeting 2018.

In the absence of other satisfactory treatment options, the panel “strongly” recommends that clinicians should give PD-1 inhibitor therapy, such as pembrolizumab, to patients who test positive for MSI/dMMR, and the TRK inhibitors larotrectinib or entrectinib to those with NTRK fusions.

Selpercatinib elicits deep antitumor responses and is well tolerated by patients with advanced non-small-cell lung cancer harboring RET fusions, show updated trial data presented at the IASLC World Conference on Lung Cancer 2019.

In the phase1b part of the trial, the researchers determined that the maximum tolerated dose for lenvatinib, which targets VEGFR1–3, FGFR1–4, PDGFRα, RET, and KIT, was 20 mg/day orally.

Phase I data indicate that the selective RET inhibitor BLU-667 elicits durable responses and is well tolerated by individuals with advanced non-small-cell lung cancer harboring a RET fusion.

Advisory Board member Ross Camidge comments on his picks for the most exciting lung cancer research being presented at the 2019 ASCO Annual Meeting, including the RELAY trial and the ARROW trial of the RET inhibitor BLU-667 (3:13).

The selective RET inhibitor LOXO-292 has activity against tumors harboring a range of RET alterations, according to findings from the first-in-human LIBRETTO-001 trial.

The remaining patients developed “unexpected” resistance mechanisms, with individual reports of RET , FGFR3 , and BRAF fusions and a KRAS Q61K mutation.

Lenvatinib is an oral multikinase inhibitor of vascular endothelial growth factor receptors 1–3, fibroblast growth factor receptors 1–4, and platelet-derived growth factor receptor α, as well as RET and KIT, he told delegates at the 2017 annual meeting of the American Society of Clinical Oncology, in Chicago, Illinois, USA.