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

Ernest Nadal; Nada Rifi; Sarah Kane; Sokhna Mbacke; Lindsey Starkman; Beatrice Suero; Hannah Le; Imtiaz A Samjoo

doi:10.1016/j.lungcan.2024.107816

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

Lung Cancer. 2024 May 9:192:107816. doi: 10.1016/j.lungcan.2024.107816. Online ahead of print.

Authors

Ernest Nadal¹, Nada Rifi², Sarah Kane³, Sokhna Mbacke³, Lindsey Starkman³, Beatrice Suero³, Hannah Le², Imtiaz A Samjoo⁴

Affiliations

¹ Department of Medical Oncology, Catalan Institute of Oncology (ICO), Avda Gran via, 199-203. L'Hospitalet, 08908, Barcelona, Spain; Preclinical and Experimental Research in Thoracic Tumors (PReTT) Group, OncoBell Program, IDIBELL, L'Hospitalet, Barcelona, Spain. Electronic address: esnadal@iconcologia.net.
² Pfizer, Inc., New York, New York, USA.
³ EVERSANA™, Burlington, Ontario, Canada.
⁴ EVERSANA™, Burlington, Ontario, Canada. Electronic address: imtiaz.samjoo@eversana.com.

PMID: 38749072
DOI: 10.1016/j.lungcan.2024.107816

Abstract

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 real-world 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®, Embase, and Cochrane CENTRAL from January 2016 to March 2023 using Ovid® 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.

Keywords: Advanced non-small cell lung cancer; Crizotinib; Meta-analysis; ROS1 gene fusion; Real-world evidence; Systematic literature review.