This analysis demonstrates continued efficacy of entrectinib in Asian patients with advanced ROS1-fp NSCLC, both overall and in the 1L setting. No new safety signals emerged.

Although NTRK-associated fusions are significant in various cancers and have led to the development of targeted therapies, such as larotrectinib and entrectinib, the specific molecular impact of atypical PRUNE2::NTRK2 fusion remains unclear. The PRUNE2::NTRK2 gene fusions described here express a non-functional TrkB protein, and it is unclear whether the PRUNE2 function is intact or affected.

This presentation aligns with a case reported in Japan, describing severe hemolytic anemia with morphological changes in erythrocytes under alectinib treatment. This is the first report describing a rapid increase in hemoglobin after pausing alectinib and no relapse of hemolysis after switching to lorlatinib, while the lung cancer remained stable (stable disease).

The mechanism of lorlatinib-induced hyperglycemia is unclear but may involve reduced insulin secretion. This case underscores the importance of monitoring for hyperglycemia in patients receiving lorlatinib, even in the absence of pre-existing diabetes, to enable early detection and prevent life-threatening complications like DKA.

This case report identifies a novel SNX25-ROS1 fusion mutation in NSCLC, showing strong sensitivity to ROS1-targeted therapy. It highlights the importance of molecular profiling in detecting rare genetic alterations and underscores the therapeutic potential of targeted treatments for NSCLC with unique molecular subtypes.

Our study reveals a novel mechanism by which the NOTCH2-NTRK1 fusion confers resistance to osimertinib through its interaction with EGFR in NSCLC.

The study confirms the marked efficacy of ALK inhibitors in ALK-positive PMP, but highlights the need to monitor neurotoxicity in adolescent patients. Through analysis of the FN1(Fibronectin 1)-ALK fusion mechanism and literature review, this study emphasizes the importance of pathological differentiation, individualized treatment, and dynamic cognitive monitoring, providing insights for precision therapy in rare diseases.

P3, N=190, Active, not recruiting, Bristol-Myers Squibb | Trial primary completion date: Mar 2027 --> Mar 2026

This case underscores the importance of molecular profiling in diagnosing metastatic tumors and confirms lorlatinib as a highly effective first-line therapy for ALK-positive non-small cell lung cancer with atypical metastases.

Here, we present a patient diagnosed with high grade metastatic inflammatory myofibroblastic tumor driven by a RANBP2::ALK fusion, who later developed an ALK G1202R resistance mutation in the setting of treatment with crizotinib. The patient remains without evidence of disease now 18 months after discontinuing adjuvant lorlatinib. This case illustrates the importance of serial molecular profiling to guide selection of the optimal ALK inhibitor for the best clinical outcomes.

This real-world analysis highlighted durable effectiveness of lorlatinib in treating NSCLC patients with ROS1 rearrangements in second-line and beyond settings. The safety profile aligned with previous clinical and real-world studies.

From the probabilistic sensitivity analysis (PSA), iruplinalkib had a 100% probability of being cost-effective at a willingness-to-pay threshold of $13,447.89/QALY. Compared to crizotinib, iruplinalkib is a cost-effective therapy for treatment-naïve patients with ALK-positive NSCLC.