ALK positive

P2, N=80, Recruiting, Stanford University | Trial primary completion date: Dec 2025 --> Dec 2026

Effective management of lorlatinib-related adverse events, through close monitoring and timely intervention, is essential to enhance patient tolerance. Lorlatinib has progressively transformed the therapeutic landscape for patients with ALK + NSCLC.

Smokers exhibited a significantly poorer OS and DMFS, and may require more risk-adapted treatment strategies, such as the combination of CRT with upfront ALK TKIs. These findings suggest that smoking may adversely affect survival by modulating the tumor immune microenvironment.

Because these disorders may be limited to the skin or be a manifestation of a systemic histiocytic neoplasm, correlation with clinical features is essential. Molecular genetic analysis to identify mutations in the mitogen-activated protein kinase pathway should be considered to provide options for targeted therapy.

After failure of gemcitabine/docetaxel chemotherapy, next-generation sequencing identified an IGFBP5-ALK fusion (breakpoint: IGFBP5 exon 1 - ALK exon 19), a TERT promoter mutation, and a homozygous CDKN2A/CDKN2B/MTAP deletion. This case highlights the first documented response to an ALK inhibitor in ALK-rearranged HG-ESS. The findings underscore the importance of comprehensive molecular profiling in identifying targetable alterations in rare sarcomas and support the use of iruplinalkib as an effective therapeutic option in this setting.

This case supports considering IMT in pediatric pelvic masses and reinforces that complete surgical resection remains the primary treatment. Although ALK gene rearrangement was not associated with therapeutic intervention in the present case, its identification remains diagnostically relevant and may provide important insights into management decisions in selected clinical scenarios, such as recurrence or unresectable disease.

P=N/A, N=800, Recruiting, Hoffmann-La Roche | Trial completion date: Dec 2029 --> Apr 2029 | Trial primary completion date: Jun 2029 --> Oct 2028

P2, N=33, Active, not recruiting, Fundación GECP | Trial primary completion date: Nov 2025 --> Nov 2026

P3, N=71, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting

Limited CIR beyond 12 months existed for brigatinib and ensartinib. Results from the Asian group's CIR aligned with global trials. Due to lower BM CIR, lorlatinib showed higher BM management cost savings compared to crizotinib and alectinib in Chinese 1 L patients.

Conditioning was based on total body irradiation (TBI) in 30 patients and on chemotherapy in 27 patients, mainly with reduced-toxicity conditioning (RTC; Treosulfan, Fludarabine, and Thiotepa). Our data support the use of TBI-free conditioning and suggest improved outcomes with unrelated donors receiving ATLG prophylaxis. NCT00317408.

Several clinical factors associated with survival were identified. Larger studies are needed to investigate how treatment sequences may be optimized to further improve survival outcomes.