ALK rearrangement

Stage III ALK-positive NSCLC is prone to relapse but local therapy combined with adjuvant ALK TKIs offers a promising strategy. Patients with EML4-ALK v1 mutations may show improved outcomes.

However, the observed outcomes should be interpreted within the context of patient selection. The enrichment for prior responders limits the generalizability to unselected post-TKI populations, including those with primary resistance.

The HEATR5B-ALK fusion is targetable by ensartinib, producing durable disease control and excellent tolerability. Comprehensive NGS and ALK IHC are essential for detecting rare actionable ALK variants.

Due to rapid enrollment, the target sample size was expanded to 28 patients. The primary endpoint is objective response rate confirmed by central assessment; secondary endpoints include duration of response, progression-free survival, overall survival, and safety.Clinical trial registration: jRCT2041210148 (https://jrct.mhlw.go.jp).

P=N/A, N=240, Completed, Bristol-Myers Squibb

P1, N=320, Recruiting, BioNTech SE | N=156 --> 320

The patient received two cycles of nab-paclitaxel and carboplatin, and repeated CT scan showed disease progression. Her treatment was subsequently changed to glumetinib plus iruplinalkib and she died less than one month later...Co-amplification of the multiple genes may be involved in aggressive disease and drug resistance, which should be considered in future clinical trials and clinical management. Early broad-panel next-generation sequencing testing in LUSCC patients who are never-smokers may help guide management for patients who have complex mutational profiles.

The study underscores the importance of integrating NGS-based molecular testing with PD-L1 evaluation for personalised management of NSCLC. Distinct patterns of PD-L1 expression across molecular subtypes, particularly lower in EGFR-mutated tumours and higher in KRAS-mutated tumours, underscore the need for tailored therapeutic strategies and informed sequencing of targeted therapies and immunotherapies.

These findings demonstrate that IHC-based screening followed by confirmatory FISH provides a rapid and cost-effective strategy for identifying cases of non-LCH with JXG morphology harboring actionable kinase alterations. Integration of IHC, FISH, and NGS represents a practical and complementary diagnostic strategy to guide precision therapy in this clinically diverse histiocytic disorder.

Finally, nutritional management is discussed, as is the role of adapted physical activity. In conclusion, this article highlights the importance of proactive monitoring and management of adverse cardiovascular events in patients treated with lorlatinib.

P4, N=41, Active, not recruiting, Guangdong Association of Clinical Trials | Not yet recruiting --> Active, not recruiting | Trial primary completion date: Jul 2025 --> Apr 2026