In metastatic ALK-positive non-small cell lung cancer (mNSCLC), ALK tyrosine kinase inhibitors (ALKi) represent the established standard of care. While second- and third-generation ALKi (including alectinib, brigatinib, ensartinib, envonalkib, and lorlatinib) have demonstrated superior efficacy compared with the first-generation inhibitor crizotinib in randomized trials, the absence of direct head-to-head comparisons limits the definition of their relative clinical benefit. We performed an updated indirect comparison of next-generation ALKi using data from pivotal randomized controlled trials. Seven first-line trials in ALK-positive mNSCLC were identified, and individual patient data were reconstructed from published Kaplan-Meier curves to estimate treatment effects using Cox proportional hazards models and restricted mean survival time (RMST) analyses, with crizotinib as a common comparator. All next-generation ALKi demonstrated significant progression-free survival (PFS) benefit versus crizotinib. In indirect comparisons, lorlatinib showed superior PFS compared with alectinib [hazard ratio (HR) 0.61; 95% confidence interval (CI): 0.43-0.85], brigatinib (HR 0.48; 95% CI: 0.33-0.71), ensartinib (HR 0.60; 95% CI: 0.40-0.90), and envonalkib (HR 0.42; 95% CI: 0.28-0.62). RMST analyses indicated increasing separation between lorlatinib and alectinib over time, suggesting a more sustained PFS benefit with lorlatinib. Among patients with baseline brain metastases (BMs), lorlatinib showed the strongest PFS effect compared with alectinib, brigatinib, ensartinib, and envonalkib. For overall survival (OS), alectinib demonstrated a statistically significant benefit versus crizotinib, while no significant differences were observed among next-generation ALKi. This indirect comparison indicates that lorlatinib provides the most durable PFS and the strongest intracranial disease control, although ALKis are characterized by distinct toxicity profiles. In the absence of clear OS differences at present, first-line treatment selection should integrate efficacy, intracranial activity, tolerability, and emerging molecular features within a personalized therapeutic framework.

Cardiac metastases are rare in clinical practice. Herein, we describe the case of a 61-year-old male patient who underwent radical left lung cancer surgery > 2 years before the current admission. The postoperative diagnosis was left lung squamous cell carcinoma (stage pT2N1M0/IIB). Post-surgery, he received adjuvant chemotherapy and did not undergo chest radiotherapy. At the current admission, the patient presented with a dull pain in the left side of his chest. Electrocardiography (ECG) revealed ST-segment elevation; repeat troponin and cardiac enzyme levels were negative. Coronary CT showed 55%-77% stenosis in the proximal-mid left anterior descending artery, but no severe occlusive disease in the other major branches. Cardiac ultrasound revealed a 104 × 49 mm hypoechoic mass at the lateral apex without regional wall motion abnormalities or pericardial effusion. Contrast-enhanced chest CT revealed a metastatic tumor in the left anterior mediastinum with invasion of the pericardium and local left ventricular wall. ST-segment elevation on ECG does not always indicate acute myocardial infarction. In patients with advanced cancer, if unexplained persistent ST elevation without pathological Q waves is observed, the possibility of cardiac metastasis should be considered.