Lorlatinib is an oral third-generation inhibitor of anaplastic lymphoma kinase (ALK) with activity in advanced ALK-positive non-small cell lung cancer (NSCLC) in both the first and subsequent line setting. Superior systemic and intracranial efficacy of lorlatinib over crizotinib, a first-generation ALK tyrosine kinase inhibitor (TKI), in treatment-naïve patients with advanced ALK-positive NSCLC was demonstrated by the phase 3 CROWN trial. Lorlatinib retains anti-tumor effect against single and some compound ALK resistance mutations after disease progression on first- and second-generation ALK TKIs. Currently, alectinib, brigatinib, ceritinib, crizotinib and lorlatinib are approved for treatment of advanced ALK-positive NSCLC. However, no head-to-head studies have directly compared lorlatinib to second-generation ALK inhibitors. Herein, we aim to provide an overview of the efficacy and safety of lorlatinib and discuss where lorlatinib stands in the therapeutic approach to advanced ALK-positive NSCLC.
Human papillomavirus (HPV)-associated head and neck squamous cell carcinomas (HNSCCs) are a subtype of virally driven tumours with favourable responses to definitive therapy. However, disease relapse or progression is clinically challenging due to limited effective treatment options. Circulating tumour DNA (ctDNA) technology has emerged in the past decade, and it remains an active area of research in head and neck cancers. A variety of assays for the analysis of HPV ctDNA in patients with HPV-positive HNSCC have been developed and studied, though standardization in HPV ctDNA testing has yet to be established. Studies show promise in HPV ctDNA as a prognostic biomarker and predictor of treatment response and risk for recurrence. Growing evidence suggests that absolute HPV ctDNA quantification, as well as dynamic changes in HPV ctDNA concentration, can potentially inform outcomes and guide decisions about therapy. The aim of this article is to review the clinical utility of HPV ctDNA as a biomarker in HNSCC.
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