Real-world safety of trastuzumab deruxtecan with gastric cancer: All-patient post-marketing surveillance study in Japan.

399 Background: Interstitial lung disease and pneumonitis (ILD/p) is an important identified risk in the Japanese risk management plan of trastuzumab deruxtecan (T-DXd). In Japan, an all-patient post-marketing surveillance (PMS) study was conducted to investigate the incidence of ILD/p and factors associated with its development among patients with gastric cancer treated with T-DXd in the real-world setting. Methods: This is an observational, multicenter, PMS study (jRCT2001200001) with an observation period of 12 months that enrolled all patients who initiated T-DXd treatment for HER2-positive unresectable advanced or recurrent gastric cancer between Sep 2020 and Dec 2021. All suspected ILD/p events reported by physicians were adjudicated by an independent ILD adjudication committee; events adjudicated as drug-related ILD/p were summarized. The factors associated with the development of adjudicated drug-related ILD/p were investigated using a Cox proportional hazards model. Effectiveness endpoints included best overall response rate according to the RECIST 1.1 and overall survival, which was estimated using the Kaplan–Meier method. Results: The safety analysis set included 1070 patients (77.4% male, 89.9% ECOG performance status ≤1) with median age of 70 years (range: 23-100). Median initial dose and treatment duration of T-DXd were 6.4 mg/kg (range: 3.1-6.4) and 3.9 months (range: 0.7-12.0), respectively.The incidence of any grade, grade ≥3, and grade 5 adjudicated drug-related ILD/p were 9.6% (n=103), 2.8% (n=30) and 1.2% (n=13), respectively. Within 24 weeks from onset, 73.8% of adjudicated drug-related ILD/p had resolved, were resolving, or resolved with sequelae.A multivariate analysis identified that medical history and/or comorbidity of ILD/p [hazard ratio (HR) = 3.372, 95% confidence interval (95% CI): 1.431, 7.840], radiation pneumonitis (HR = 8.523, 95% CI: 2.006, 36.215), COPD or emphysema (HR = 1.962, 95% CI: 1.032, 3.731) and age ≥75 years (HR = 1.648, 95% CI: 1.058, 2.567) were factors of interest associated with the development of ILD/p in patients with gastric cancer. The overall response rate at 12 months post-treatment initiation of T-DXd was 34.2%. Overall survival after 364 days post-treatment initiation of T-DXd was 43.8% (median survival time: 303.0 days). Conclusions: The results suggest that the risk of ILD/p in this PMS study does not differ from that in the Destiny Gastric-01 study, and no new safety concerns were identified. Medical history and/or comorbidity of ILD/p, radiation pneumonitis, COPD or emphysema and age ≥75 years were identified as factors of interest associated with the development of ILD/p in patients with gastric cancer. Further investigation into the identified factors of interest may offer insights into the development of ILD/p among T-DXd treated gastric cancer patients in Japan. Clinical trial information: jRCT2001200001.