Efficacy and safety of trastuzumab deruxtecan in gastrointestinal malignancies: A systemic review and meta-analysis.

Abstract

e16468 Background: Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate (ADC) that has demonstrated efficacy in treating a variety of gastrointestinal (GI) cancers. However, there is significant variability in its reported efficacy and safety profiles, likely due to differences in trial designs, patient populations, and clinical settings. This systematic review and meta-analysis aims to consolidate current evidence on the efficacy and safety of T-DXd in GI malignancies. Methods: We conducted a systematic review and meta-analysis following PRISMA guidelines, utilizing the Medline, Embase, Cochrane Central, and ClinicalTrials.gov databases. Out of 5,594 articles reviewed, ten studies were ultimately included after both primary and secondary screenings, providing data on the outcomes and safety of T-DXd in GI malignancies. The NIH quality assessment tool was employed to evaluate the quality of the studies. Pooled analyses were performed using the 'meta' package (Schwarzer et al., R programming language), and proportions with 95% confidence intervals (CIs) were calculated. Results: We identified ten studies involving 653 patients treated with T-DXd for GI malignancies. The median age of the patients was 64.5 years (27-85), with 53% being male. The median follow-up duration was 5.9 months (0.5-30.5). The median overall survival and progression-free survival were 11.15 months (1.4-20.8) and 5.6 months (2.6-8.7), respectively. The pooled objective response rate (ORR) was 36.9% (95% CI: 31.5%-42.5%, I² = 41%, n = 589), with partial response and complete response rates of 35.2% (95% CI: 31.1%-39.5%, I² = 0%, n = 516) and 1.3% (95% CI: 0.0%-4.7%, I² = 73%, n = 516), respectively. The median duration of response (DoR) was seven months (0.7-22.3). Reported adverse events included anemia, febrile neutropenia, thrombocytopenia, diarrhea, nausea, interstitial lung disease/pneumonitis, heart failure, and hepatitis. Eight out of ten studies noted treatment discontinuation due to toxicities in 77 patients. For the 5.4 mg/kg dose, grade 3/4 adverse events were reported in 67 patients by two studies. For the 6.4 mg/kg dose, a total of 146 grade 3/4 adverse events were reported by six studies. Conclusions: This meta-analysis supports the efficacy of T-DXd in patients with GI malignancies, demonstrating a moderate ORR and a clinically meaningful DoR, even in patients who have experienced disease progression after multiple lines of therapy. Overall, T-DXd is well-tolerated, with minimal severe adverse events. These findings validate existing research and underscore the need for further clinical trials, particularly in earlier lines of treatment. The evolving landscape of ADCs, including T-DXd, highlights the importance of continued research and clinical application across various malignancies.