RET Solvent Front Mutations Mediate Acquired Resistance to Selective RET Inhibition in RET-Driven MalignanciesNovel rearranged in transfection (RET)-specific tyrosine kinase inhibitors (TKIs) such as selpercatinib (LOXO-292) have shown unprecedented efficacy in tumors positive for RET fusions or mutations, notably RET fusion-positive NSCLC and RET-mutated medullary thyroid cancer (MTC). However, the mechanisms of resistance to these agents have not yet been described.
Increased Hepatotoxicity Associated with Sequential Immune Checkpoint Inhibitor and Crizotinib Therapy in Patients with Non–Small Cell Lung CancerImmune checkpoint inhibitors (ICIs) are standard therapies in advanced NSCLC. Although genotype-directed tyrosine kinase inhibitors represent the standard of care for subsets of oncogene-driven NSCLC, patients may receive ICIs during their disease course. The impact of sequential ICI and tyrosine kinase inhibitor therapy on the risk of hepatotoxicity has not been described.
Brigatinib in Patients With Alectinib-Refractory ALK-Positive NSCLCThe second-generation anaplastic lymphoma kinase (ALK) inhibitor alectinib recently showed superior efficacy compared to the first-generation ALK inhibitor crizotinib in advanced ALK-rearranged NSCLC, establishing alectinib as the new standard first-line therapy. Brigatinib, another second-generation ALK inhibitor, has shown substantial activity in patients with crizotinib-refractory ALK-positive NSCLC; however, its activity in the alectinib-refractory setting is unknown.
Safety of Combined PD-1 Pathway Inhibition and Intracranial Radiation Therapy in Non–Small Cell Lung CancerIntracranial metastases are a common cause of morbidity and mortality in patients with advanced NSCLC, and are frequently managed with radiation therapy (RT). The safety of cranial RT in the setting of treatment with immune checkpoint inhibitors (ICIs) has not been established.
ROS1 Fusions Rarely Overlap with Other Oncogenic Drivers in Non–Small Cell Lung CancerChromosomal rearrangements involving the gene ROS1 define a distinct molecular subset of NSCLCs with sensitivity to ROS1 inhibitors. Recent reports have suggested a significant overlap between ROS1 fusions and other oncogenic driver alterations, including mutations in EGFR and KRAS.
Clinical Activity of Alectinib in Advanced RET-Rearranged Non–Small Cell Lung CancerChromosomal rearrangements involving rearranged during transfection gene (RET) occur in 1% to 2% of NSCLCs and may confer sensitivity to rearranged during transfection (RET) inhibitors. Alectinib is an anaplastic lymphoma kinase tyrosine kinase inhibitor (TKI) that also has anti-RET activity in vitro. The clinical activity of alectinib in patients with RET-rearranged NSCLC has not yet been reported.
Clinicopathologic Features of NSCLC Diagnosed During Pregnancy or the Peripartum Period in the Era of Molecular GenotypingCancer will be diagnosed in one in 1000 women during pregnancy. The outcomes of NSCLC diagnosed during pregnancy are dismal, with most patients dying within 1 year. Actionable mutations are more likely to be found among younger patients with NSCLC. However, most previous reports of NSCLC diagnosed during pregnancy did not include molecular genotyping.
Alectinib Salvages CNS Relapses in ALK-Positive Lung Cancer Patients Previously Treated with Crizotinib and CeritinibLeptomeningeal metastases (LM) are an increasingly frequent and devastating complication of anaplastic lymphoma kinase (ALK)-rearranged non–small-cell lung cancer (NSCLC). Currently, the optimal management of LM in ALK-positive patients remains poorly understood as these patients have been routinely excluded from clinical trials.