Efficacy and safety of taletrectinib for treatment of ROS1 positive non-small cell lung cancer: A systematic review

Abstract

Introduction: Approximately 85% of all instances of lung cancer are non-small-cell lung cancer (NSCLC). Crizotinib and entrectinib are the preferred first line therapy for treating ROS1 fusion-positive NSCLC (ROS1+NSCLC). However, not all patients react to these treatments and most of the patients acquire resistance to the medications. Taletrectinib is intended to address few of the issues with these treatments, such as lowering tyrosine receptor kinase B TRKB-related neurological side events by selectively inhibiting ROS1 over TRKB, addressing tumor treatment resistance and brain metastases through blood-brain barrier penetration.

Methods: A systematic literature search was conducted across PubMed, ScienceDirect, Cochrane, and ClinicalTrials.gov upto September 2024. Studies were included if they investigated taletrectinib for ROS1-positive NSCLC.

Results: Out of 392 identified records, three studies involving 234 participants (102 males, 132 females) met inclusion criteria. Taletrectinib demonstrated high overall response rates (ORR) in treatment-naïve patients (upto 90.6%) and moderate ORR (51.5%) in crizotinib-pretreated patients. It showed manageable adverse events, such as mild liver enzyme elevations and gastrointestinal symptoms.

Conclusions: Taletrectinib shows significant efficacy and favorable safety profile for ROS1-positive NSCLC, particularly in treatment-naïve or tyrosine kinase inhibitor TKI-resistant patients. Further large-scale trials are warranted to confirm its long-term safety and efficacy.

Keywords: AB-106/DS-6051b; NSCLC; Non-small-cell lung cancer; ROS1 fusion-positive; Taletrectinib.