Efficacy and safety of crizotinib in the treatment of advanced non-small cell Lung cancer with ROS1 gene fusion: A systematic literature review and Meta-Analysis of real-world evidence

Background: Crizotinib was approved to treat patients with advanced non -small cell lung cancer (aNSCLC) with ROS proto-oncogene 1 (ROS1) gene fusion in 2016. We conducted a systematic literature review to identify realworld evidence (RWE) studies and estimated the efficacy and safety of crizotinib using meta-analyses (MA) for objective response rate (ORR), real -world progression -free survival (PFS), and overall survival (OS). Methods: We searched MEDLINE (R), Embase, and Cochrane CENTRAL from January 2016 to March 2023 using Ovid (R) for published single -arm or comparative RWE studies evaluating patients (N >= 20) receiving crizotinib monotherapy for aNSCLC with ROS1 gene fusion. Pooled estimates for ORR and grade 3/4 adverse events (AEs) were derived using the metafor package in R while pooled estimates for median real -world PFS (rwPFS) and OS were derived using reconstructed individual patient data from published Kaplan -Meier curves. The primary analysis included all studies regardless of crizotinib line of therapy; a subgroup analysis (SA) was conducted using studies evaluating patients receiving first -line crizotinib. Results: Fourteen studies met the eligibility criteria and were considered feasible for MA. For the primary analysis, the pooled ORR (N = 9 studies) was 70.6 % (95 % confidence interval [CI]: 57.0, 81.3), median rwPFS was 14.5 months (N = 11 studies), and OS was 40.2 months (N = 9 studies). In the SA, the pooled ORR (N = 4 studies) was 81.1 % (95 % CI: 76.1, 85.2) and the median rwPFS (N = 4 studies) and OS (N = 2 studies) were 18.1 and 60 months, respectively. All MAs were associated with significant heterogeneity (I2 > 25 %). Grade 3/4 AEs occurred in 18.7 % of patients (pooled estimate). Conclusion: The results from this study are consistent with clinical trial data and, taken collectively, supports crizotinib as a safe and effective treatment across different lines of therapy in patients with ROS1 aNSCLC in the real -world setting

Copper-Catalyzed Electrophilic Carbofunctionalization of Alkynes to Highly Functionalized Tetrasubstituted Alkenes

Copper catalysts enable the electrophilic carbofunctionalization of alkynes with vinyl- and diaryliodonium triflates. The new process forms highly substituted alkenyl triflates from a range of alkynes via a pathway that is opposite to classical carbometalation. The alkenyl triflate products can be elaborated through cross-coupling reactions to generate synthetically useful tetrasubstituted alkene