Entrectinib in Asian patients with ROS1 fusion-positive non-small cell lung cancer: updated efficacy and safety analysis.

Anaplastic thyroid cancer (ATC) is a rare and aggressive malignancy with limited treatment options and a poor prognosis. This study evaluates the outcomes of patients with locally advanced or metastatic ATC treated at two tertiary centres, focusing on the efficacy of pembrolizumab and lenvatinib, and the impact of BRAF status. A retrospective review of 16 ATC patients treated between January 2018 and June 2024 at two tertiary Australian hospitals was conducted. Pathological confirmation was required for inclusion. Clinical data, including treatment regimens, response rates assessed by Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1), progression-free survival (PFS), and overall survival (OS), were analysed. Fifteen out of 16 patients (94%) had metastatic disease. Five patients (31%) had a BRAFV600E mutation, with four receiving first-line (1L) dabrafenib/trametinib, achieving a 75% (3/4) objective response rate. Eleven patients (50%) were BRAF wildtype, and eight received pembrolizumab and lenvatinib as both 1L and second-line (2L) settings, with an objective response rate of 75% (6/8) in both 1L and 2L settings, including three complete responses. Programmed death-ligand 1 tumour proportional score ≥50% was found in 64% (9/14) of patients, correlating with better outcomes. Median time on treatment for the pembrolizumab and lenvatinib group was not reached, with the longest survival exceeding 12 months at the time of data cut-off. This case series highlights promising outcomes with systemic treatment options in ATC, but the analysis is limited by a small sample size, emphasising the need for further research and collaboration to improve clinical outcomes.

BackgroundOptimal management of extensive-stage small-cell lung cancer (ES-SCLC) following progression on first-line (1L) chemoimmunotherapy remains undefined. This study aimed to evaluate the efficacy of immune checkpoint inhibitors (ICIs) continuation in a second-line (2L) treatment setting.MethodsA total of 211 ES-SCLC patients with disease progression after 1L chemoimmunotherapy were analyzed retrospectively after stratifying them into ICIs continuation (n = 118) and ICIs discontinuation (n = 93) cohorts. The primary endpoint was 2L overall survival (2L-OS), and the secondary endpoints included 2L progression-free survival (2L-PFS), objective response rate (2L-ORR), disease control rate (2L-DCR), and safety. Propensity score matching (PSM, 1:1) ensured balanced baseline characteristics. Survival analyses were conducted based on Kaplan-Meier curves. Univariate and multivariate Cox regression analyses were performed to identify the factors associated with 2L-PFS and 2L-OS.ResultsICIs continuation significantly improved 2L-OS (8.66 vs 7.90 months; P = 0.016) and 2L-PFS (3.92 vs. 2.15 months; P < 0.001). The benefits of ICIs continuation persisted after PSM (2L-OS: 10.31 vs. 8.95 months, P = 0.027; 2L-PFS: 4.22 vs.2.12 months, P < 0.001). In addition, the ICIs continuation group demonstrated superior tumor response (2L-ORR: 28.8% vs. 11.8%, P = 0.003; 2L-DCR: 65.3% vs. 44.1%, P = 0.002), which remained significant post-PSM. Treatment-related adverse events (AEs) were comparable between the groups, while immune-related AEs were predominantly low grade in the ICIs continuation group. Multivariate analysis revealed that baseline liver metastasis and 1L-PFS were independent risk factors for 2L-PFS and 2L-OS, whereas overweight (BMI 25.0-29.9) was an independent prognostic factor for 2L-OS. The exploratory analysis conducted for the ICIs continuation cohort revealed no significant difference in patient survival between the continuing ICIs treatment group and switching ICIs treatment group (2L-OS: P = 0.668; 2L-PFS: P = 0.346).ConclusionIn patients with ES-SCLC who exhibit disease progression after 1L chemoimmunotherapy, continuation of ICIs significantly improves survival and tumor response while achieving a manageable safety profile. Therefore, ICIs continuation may be considered a viable strategy in 2L settings.

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