Analysis of Adverse Events Associated with Trastuzumab Deruxtecan in Patients with Gastric and Breast Cancer: A Retrospective Study.

Trastuzumab deruxtecan (T-DXd) has displayed demonstrable efficacy and manageable toxicity in previously treated patients with advanced gastric and breast cancer, and it has been approved in Japan. However, there is a lack of data on the optimal management in clinical practice. Therefore, we assessed the adverse event (AE) profiles of T-DXd in patients with advanced gastric or breast cancer to provide guidance for appropriate management. This retrospective study was conducted at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research. We reviewed the medical records of patients with advanced gastric or breast cancer who received T-DXd between May 2020 and December 2021. AEs occurring within the first three cycles of T-DXd were evaluated according to Common Terminology Criteria for Adverse Events version 5.0. Thirty-six patients were enrolled (gastric: n = 19, breast: n = 17). All 15 males had gastric cancer, whereas 4 and 17 females had gastric and breast cancer, respectively. Interstitial lung disease (ILD) occurred in five patients (14%), but no patients had severe ILD. Gastrointestinal (GI) toxicities, including nausea (61%), vomiting (22%), decreased appetite (33%), and diarrhea (39%), were the most common AEs. The incidence of GI toxicities did not differ by cancer type; however, nausea was significantly more common in females (81 vs. 33%; p < 0.01). T-DXd was safely administered in clinical practice in patients with previously treated advanced gastric or breast cancer. The management of GI toxicities is important in the clinical implementation of T-DXd.

Serum Creatinine Elevation as a Risk Factor for Niraparib-induced Hematologic Toxicity.

BACKGROUND/AIM: Niraparib dosages can be individualized to reduce the starting dose based on body weight and baseline platelet count. However, even with individualized dosing, scattered cases of ≥Grade 3 hematologic toxicity occur. This study explored markers predictive of serious hematologic toxicity in niraparib therapy. PATIENTS AND METHODS: This retrospective observational study investigated patients who started niraparib therapy at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research between December 2020 and March 2022. Associations between hematologic toxicities and serum creatinine ratio (percentage increase in serum creatinine between baseline and after niraparib initiation) were investigated. RESULTS: Out of 50 ovarian cancer patients who initiated niraparib, 45 patients were included in the final analysis. Twenty-three patients (51.1%) developed ≥Grade 3 hematologic toxicity, with neutropenia in 17 (37.8%), anemia in 9 (20.0%), and thrombocytopenia in 4 (8.9%). Patients with Grade 4 hematologic toxicity showed higher serum creatinine ratios than those with ≤Grade 2. Thrombocytopenia ≥Grade 3 occurred only within 2 months of niraparib initiation and was preceded by an increase in serum creatinine in all affected patients. CONCLUSION: Serum creatinine ratio offers a potential marker for predicting severe hematologic toxicity following niraparib therapy.

Factors Associated With Regorafenib Adherence With Metastatic Colorectal Cancer.

INTRODUCTION: Regorafenib is an oral multikinase inhibitor for the treatment of metastatic colorectal cancer (mCRC). The clinical factors that may affect adherence to regorafenib remain unclear. The aim of this study was to evaluate adherence to regorafenib with mCRC and to identify factors that might affect adherence to regorafenib. METHODS: A total of 108 consecutively enrolled Japanese patients with mCRC received regorafenib. Adherence was measured by pharmacists using pill counts and a self-reported treatment diary for patients at a pharmaceutical outpatient clinic. The median relative dose intensities of regorafenib and the factors adversely affecting adherence were retrospectively surveyed. Logistic regression analysis was then performed using patient socio-demographic factors and clinical factors. RESULTS: A total of 96 patients were included in the analysis. The median adherence rate was 61.7% in the first cycle. The median relative dose intensity was 57.1%. The most common reason for non-adherence was a hand-foot-skin reaction (35.6%). On multivariate analysis, increased non-adherence to regorafenib was significantly associated with sex (female) [odds ratio (OR) = 4.36; 95% confidence interval (CI): 1.43-13.22, p = 0.01]. DISCUSSION: Hand-foot-skin reactions and female sex were associated with lower adherence to regorafenib. Since these factors could be associated with lower adherence to regorafenib, it would be useful to consider these factors when assessing adherence.