Abstract P4-07-02: Toxicity profile of single agent trastuzumab deruxtecan in solid tumors: A meta-analysis
Authors: Tamimi Faris , Mittal Abhenil , Valiente Consolacion Molto , Iorio Massimo Di , Al-Showbaki Laith , Nadler Michelle , Amir Eitan 
Published: March 2023

Abstract
Background: Trastuzumab deruxtecan (T-DXd) has been evaluated in numerous solid tumors and has been approved for metastatic HER2-positive breast and gastric/gastroesophageal cancers. We aimed to provide a precise estimate of toxicity of T-DXd observed in clinical trials. Methods: A systematic literature search was performed in PubMed and supplemented by review of abstracts from ASCO and ESMO. Eligible studies were clinical trials (dose-expansion phase 1, phase 2, and phase 3) investigating single agent T-DXd. The search was performed in June 2022. For single-arm trials, meta-analysis comprised one-sample proportions to obtain the random effects estimates of toxicity and respective 95% confidence intervals (CI) for T-DXd, while for randomized trials, the Mantel-Haenszel odds ratio method was utilized. Results: Fifteen trials comprising 1566 participants were evaluable for toxicity. ECOG Performance Status (PS) was reported in 11 studies and was ≥ 2 in only a single patient. The median age at enrollment was reported for 13 studies and was 57.5 years. Seven trials comprising 1023 (65.3%) participants evaluated T-DXd for breast cancer. From available data, 1209/1440 (84%)of participants were female and 735/1551 (47%) were from East Asia. The median follow-up time was 11.1 months (13 studies) and median previous lines of treatment were 3 (12 studies). All-grade toxicity rate of ≥10% was reported for most toxicities; however, grade ≥3 toxicity rate of ≥10% was reported only for neutropenia and anemia; 17.4% (95%CI 12-22.8) and 14.8% (95%CI 8.6-21), respectively (Table 1). Interstitial lung disease/pneumonitis (ILD) was reported in 203 (12.4%) patients, including 160 (9.41%) grade 1-2, and 23 (1.1%) grade 3-4. Treatment-related death was reported in 20 (1%) patients, and all were due to grade 5 ILD. No significant difference in ILD was identified in subgroup analysis of trials conducted in east Asia vs. the rest of the world, breast vs. other solid tumors, 5.4mg/kg vs. other doses, median follow-up &lt; 12 months vs. ≥12 months or median previous lines ≥3 vs. &lt; 3. In the three randomized clinical trials, grade ≥3 toxicity was significantly higher for nausea (OR: 9.32, 95%CI: 2.53-34.32), ILD (OR: 5.35, 95%CI: 0.97, 29.48), fatigue (OR:2.5, 95%CI: 1.11-5.66), and anemia (OR:1.77 95%CI: 1.14-2.74). Conclusions: T-DXd was associated with infrequent grade ≥3 toxicities across clinical trials. Grade 1-2 ILD was more common; however, grade 3-4 ILD occurred in 1.1%. This may be related to active monitoring of this toxicity in clinical trials and discontinuation of treatment in participants with G2 ILD. There is lack of evidence for the safety of T-DXd in patients with ECOG PS ≥ 2.
Citation Format: Faris Tamimi, Abhenil Mittal, Consolacion Molto Valiente, Massimo Di Iorio, Laith Al-Showbaki, Michelle Nadler, Eitan Amir. Toxicity profile of single agent trastuzumab deruxtecan in solid tumors: A meta-analysis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-02.