A meta-analysis analyzing the efficacy and safety of datopotamab deruxtecan (Dato-DXd) in previously treated patients with non-small cell lung cancer (NSCLC).

Abstract

e20674 Background: Dato-DXd is an antibody-drug conjugate with a TROP2-directed monoclonal antibody. Recent trials have demonstrated promising efficacy for Dato-DXd in pre-treated advanced NSCLC compared to 2nd line chemotherapy. Methods: A systematic search using terms encompassing Dato-DXd and NSCLC was conducted in PubMed, Embase, Cochrane and Scopus. A total of 2866 records were identified and imported into Rayyan. These were screened independently by two reviewers, and a third independent reviewer resolved conflicts. 56 studies were included for full text screening subsequent to which 5 studies were included for final analysis. All 5 studies were randomized controlled trials that studied Dato-DXd. 3 were full text articles, and 2 were abstracts. Binary Random-effects (RE) model pooled proportions (PP) using DerSimonian-Laird method was performed using OpenMeta. Results: A total of 756 patients were included from 5 studies. All studies included patients with advanced stage NSCLC who had received 1-5 prior lines of therapy. 4 studies used a standard Dato-DXd dose of 6mg/kg every 3 weeks while one study divided patients into 4mg/kg, 6mg/kg and 8mg/kg every 3-weeks groups. Disease Control Rate (DCR) ie CR+PR+SD was seen in 77.1% [(74.2-80.1) I2=0%]. Overall Response Rate (ORR) ie CR+PR was seen in 30.8% [(26.8-34.9) I2=24.4%]. Mortality rate was 62.8% [(49.7-76.0) I2=89.3%]. Pooled mean OS was 12.1 months (8.4-15.3), PFS was 5.5 (3.4-7.2). Pooled mean for median time to response was 1.4 months (1.2-9.7), median duration of response (DOR) was 9.6 (4.6-18.2). Stomatitis was seen in 55.5% [(50.0-60.9) I2=50.7%]. Pneumonitis was seen in 5.4% [(2.2-8.6) I2=78.8%]. Drug discontinuation due to adverse effects occurred in 11.5% [(6.7-16.2) I2=70.6%]. Rest of analytic statistics shown in Table 1. Conclusions: Pooled data for Dato-DXd in the subsequent line setting demonstrated a robust overall response rate and disease control rate.In comparison DCR for docetaxel and ramucirumab in the REVEL study was 67%. Based on this, Dato-DXD could be a subsequent line treatment option in metastatic NSCLC. While meta-analysis results can be confounded by heterogeneity between studies, results of ongoing clinical studies on Dato-Dxd that may result in the near future may help better answer this question. Pooled proportion metrics for Dato-DXd in pretreated advanced NSCLC. Dato-DXd in pretreated NSCLC % (95% CI) I 2 Partial Response (PR) 27.7% (22.4-32.9) 48% Complete Response (CR) 1.4% (0.5-2.3) 0% Stable Disease (SD) 47.2% (42.2-52.2) 27.5% Progressive Disease (PD) 14.3% (11.5-17.0) 0% Overall response rate (ORR) 30.8% (26.8-34.9) 24.4% Disease Control rate (DCR) 77.1% (74.2-80.1) 0% Grade 3 or worse adverse effects (AE) 38.8% (28.3-49.4) 88.9% Pneumonitis 5.4% (2.2-8.6) 78.8% Stomatitis 55.5% (50.0-60.9) 50.7%