ROS1 rearrangement

This is the largest NSCLC dataset analyzed for biomarker distribution across histologies, age, sex and genetic ancestry. This dataset confirms sufficient enough biomarker prevalence across many histological subtypes of NSCLC, providing reassurance that all NSCLC cases should be considered for biomarker workup.

Our report underscores the critical need for rigorous thromboembolic monitoring in pregnant patients undergoing cancer treatment. Furthermore, we provide evidence that placental tissue significantly reduces fetal crizotinib exposure, suggesting that crizotinib might be a viable therapeutic option for maintaining a pregnancy during lung cancer treatment.

Peripheral monocyte profiling of the patient post-Repotrectinib and localized radiotherapy showed 75% CD8+/CD3 + T cells, 14.2% CD4+/CD3 + T cells, 3.95% regulatory T cells (Tregs), and 38% PD-1 + CD3 + T cells...Furthermore, we also provide a comprehensive review of recent clinical advancements in ALK/ROS1-TKI for NSCLC, including mechanistic insights into TKI resistance development. This case underscores the therapeutic potential of molecular-targeted agents in LUSC and highlights the essential role of NGS-guided precision oncology.

P3, N=675, Recruiting, AstraZeneca | Trial completion date: May 2030 --> Dec 2029 | Trial primary completion date: Apr 2028 --> Dec 2029

P1/2, N=28, Terminated, Xencor, Inc. | N=168 --> 28 | Trial completion date: Oct 2027 --> Dec 2025 | Recruiting --> Terminated | Trial primary completion date: Oct 2026 --> Dec 2025; Business Decision

P1/2, N=9, Recruiting, West China Hospital | Not yet recruiting --> Recruiting | Initiation date: Jul 2025 --> Dec 2025 | Trial primary completion date: Jul 2025 --> Jun 2027

The overall concordance of genotyping results between cfRNA-protected SS and paired CNB specimens was 100%, correctly identifying all ALK fusions, ROS1 rearrangements, and MET-14 skipping alterations. These findings highlight that preserving cfRNA in CNB-SS from NSCLC can improve the performance of genomic testing, particularly for RNA-based assays, without compromising the accuracy of DNA-based assays.

P1/2, N=80, Completed, Institut Bergonie | Active, not recruiting --> Completed

Here, we report a lung IMT in a 45-year-old female demonstrating a unique meningothelial-like pattern, equivocal ALK expression (negative for clone 5A4 and positive for clone ALK1), negative ALK rearrangement by FISH, and the presence of the TPM3::ALK fusion. To our knowledge, this is the first reported case of lung IMT displaying meningothelial-like whorls, with a particular focus on differential diagnosis.

Multiple ROS1 tyrosine kinase inhibitors (TKIs)-from crizotinib to newer agents such as entrectinib, lorlatinib, repotrectinib, taletrectinib, and the highly selective zidesamtinib-have improved systemic and intracranial outcomes, although resistance remains inevitable and biologically diverse, involving both on-target kinase mutations and off-target mechanisms...Pemetrexed-based chemotherapy remains an effective option, whereas immune checkpoint inhibitors provide limited benefit...Looking ahead, priorities include optimizing sequencing strategies, evaluating perioperative targeted approaches, and incorporating genomic monitoring to anticipate resistance. These advances are reshaping the natural history of ROS1-rearranged NSCLC and supporting a more durable, precision-driven treatment paradigm.

Regimens co-targeting the MAPK pathway and ALK or ROS1 had limited efficacy in unselected patients with lorlatinib-resistant NSCLC, underscoring the need for more effective and biomarker-informed treatment strategies.

The efficacy of crizotinib in this molecular subset demonstrates favorable clinical outcomes. Furthermore, considering the relatively high prevalence of ROS1 co-mutations with other genetic alterations in these cases, multi-targeted combination therapy may represent a promising therapeutic strategy for this distinct patient population.