A meta-analysis of safety and efficacy of datopotamab deruxtecan and sacituzumab govitecan for second line treatment of metastatic non-small cell lung cancer (NSCLC).

Abstract

8575 Background: Subsequent line treatment options for metastatic NSCLC remain limited. We sought to analyze the efficacy and safety of two Anti-TROP-2/topoisomerase inhibitor antibody-drug conjugates (ADCs), sacituzumab govitecan (SG) and datopotamab deruxtecan (Dato-DXd), for NSCLC treatment via a meta-analysis. Methods: A systematic search in PubMed, Scopus, and Cochrane identified 2348 studies. After excluding duplicates (1263) and screening abstracts (1085), 25 studies underwent full-text review, and 5 RCTs (3 Dato-DXd, 2 SG) were included. All included studies involved patients with advanced NSCLC that progressed on first-line treatment. Binary random effects and pooled proportions were calculated separately for Dato-DXd and SG using OpenMeta. The Mantel-Haenszel method with random effects estimated risk ratios and odds ratios with 95% confidence intervals for ADCs vs. docetaxel. Heterogeneity was assessed using I² statistics. Results: 616 Dato-DXd and 353 SG patients were included. Pooled proportions (PP) for grade 3 adverse events were 34.0% (Dato-DXd) and 75.4% (SG) while drug discontinuation rates were 7.1% (Dato-DXd) and 7.0% (SG), respectively. Efficacy outcomes included event rate, disease control rate, and overall response rate. For Dato-DXd, these pooled proportions were 52.0%, 76.5%, and 29.4%; for SG, they were 44.8%, 67.6%, and 14.3%. PPs and relevant statistics are included in table 1. When compared to docetaxel, combined ADCs showed no significant risk reduction in progression [RR: 0.96 (0.89 – 1.05), p=0.40, I²=7%] or mortality [RR: 0.90 (0.58 – 1.38), p=0.63, I²=43%]. Odds ratios for disease control rate [1.39 (0.76 – 2.54), p=0.29, I²=83%] and overall response rate [1.33 (0.40 – 4.42), p=0.64, I²=94%] were also insignificant. Conclusions: Direct comparisons between ADC (Dato-Dxd and SG) and docetaxel did not show a significant difference in disease progression or death rate. This study was limited by the small number of participants and heterogeneity of published literature as many clinical trials are still ongoing. Despite this, SG and Dato-DXd had a promising overall response rate of 67.6% and 76.5%, respectively. Pooled proportions of Dato-Dxd and SG to docetaxel. Datopotamab Deruxtecan Sacituzumab Govitecan Value 95% CI P-Value I² Value 95% CI P-Value I² Event Rate 0.520 (0.258, 0.782) <0.001 97% 0.448 (0.211, 0.686) <0.001 90.8% DCR 0.765 (0.727, 0.803) <0.001 0% 0.676 (0.627, 0.726) <0.001 0% ORR 0.294 (0.230, 0.358) <0.001 49.6% 0.143 (0.106, 0.180) <0.001 0% G3AER 0.340 (0.215, 0.465) <0.001 86% 0.754 (0.572, 0.937) <0.001 91.1% DDR 0.071 (0.026, 0.116) 0.002 69.1% 0.070 (0.011, 0.130) 0.20 74.2% Abbreviations: DCR, disease control rate; ORR, overall response rate; G3AER, grade 3 adverse events rate; DDR, drug discontinuation rate.