ROS1 rearrangement

Furthermore, this case describes a rare presentation of a ROS1 alteration in SCC of the lung. This illustrates the importance of routine comprehensive genomic profiling in lung cancer patients regardless of histology and smoking status.

Crizotinib, entrectinib, and repotrectinib have been approved by the US Food and Drug Administration for treatment of ROS1-positive NSCLC. In this nonrandomized clinical trial, lorlatinib demonstrated durable efficacy and manageable safety in TKI-naive advanced ROS1-positive NSCLC, supporting the potential for using lorlatinib in earlier treatment settings. ClinicalTrials.gov Identifier: NCT03612154.

The safety profile of crizotinib remained consistent with previous reports, with most adverse events being grade 1 or 2 and no new safety concerns identified. This analysis supports the efficacy of crizotinib in patients with advanced NSCLC and ROS1 rearrangements, although its activity in patients with BM remains limited, highlighting the need for brain-penetrant tyrosine kinase inhibitors to improve outcomes in this patient group.

P1/2, N=862, Recruiting, DualityBio Inc. | Trial completion date: Jan 2028 --> May 2028 | Trial primary completion date: Sep 2027 --> Dec 2027

P2, N=12, Terminated, Oncology Institute of Southern Switzerland | Trial completion date: Dec 2024 --> May 2025 | Active, not recruiting --> Terminated; Terminated for futility, as determined by an interim data analysis.

The patient received first-line chemotherapy with pemetrexed (820 mg on day 1) plus cisplatin (40 mg on days 1-3) every 21 days and achieved a remarkable progression-free survival (PFS) of 48 months...She was subsequently treated with ensartinib (225 mg once daily), yielding a favorable response...Unless there are studies with large cohorts clarifying the case, an individualized regimen-potentially starting with chemotherapy and transitioning to targeted agents-may be justified. Further clinical experience and collaborative research are essential to develop evidence-based guidelines for this exceptionally rare subset.

Canonical fusion partners with introns 33 and 34 of ROS1 may be the most optimal predictors for ROS1-TKI benefit. Precise characterization of the variants in terms of ROS1 breakpoints could be important for patient stratification in ROS1-rearranged cancers.

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.

RICTOR mutations in lung adenocarcinoma define a molecularly distinct subgroup characterized by preferential co-occurrence with EGFR, KRAS, and TP53, as well as a broader spectrum of genomic alterations. These findings support the view that RICTOR functions within complex oncogenic contexts and warrant further investigation in larger, multi-institutional cohorts.

Importantly, we identified ROS1 p.K1991N as a potential acquired drug resistance mutation to crizotinib, suggesting that entrectinib may serve as a targeted therapy to overcome this resistance mechanism. ROS1 rearrangement could potentially represent a novel driver mutation in MPM, especially in female adults. This case report illustrates the benefits of molecular detection in MPM and underscores the potential for lessons learned from other solid tumors to inform treatment strategies for rare diseases.

The debate over STAS as a true invasion mechanism versus an artifact from surgical handling underscores the need for standardized pathological evaluation. This review aims to refine STAS detection, integrate it into multidisciplinary treatment decision-making, and assess its potential as a staging criterion in lung cancer management.

Comprehensive testing for somatic alterations in EGFR, BRAF, KRAS, and PIK3CA is significant in guiding therapeutic decisions in lung cancer management. Such testing should be routinely conducted to establish a thorough genetic profile of lung cancers in a manner that is both time-efficient and cost-effective.