Presenting Author: Matt Arango, PharmD, BCOP, The Ohio State University James Cancer Center, Columbus, OH
Co-Authors: Hiba Alzouby, PharmD, BCOP, Ning Jin, MD, Ashish Manne, MBBS, Arjun Mittra, MD, and Anne Noonan, MB ChB, PhD, The Ohio State University James Cancer Center, Columbus, OH
BACKGROUND: Fam-trastuzumab deruxtecan (TDxd) is approved for use in advanced gastric/gastroesophageal junction cancer (aGC) as well as any HER2-positive solid tumor. There are differences in dosing and in HER2 testing methodology in the studies used to support the aGC and solid tumor indications. It is hypothesized that the higher dose recommended for aGC may lead to greater adverse events, potentially negating benefit. Furthermore, not retesting for HER2 status after failure of previous anti-HER2 therapy in aGC could miss patients whose tumors no longer express HER2.
OBJECTIVES: To describe the efficacy and safety of TDxd in patients receiving treatment for aGC in a gastrointestinal medical oncology clinic at a large comprehensive cancer center. The secondary objectives include determining the median starting dose and relative dose intensity and describing the patterns of use in terms of line of therapy and HER2 testing before the initiation of TDxd.
METHODS: A retrospective chart review was conducted that included patients who initiated TDxd for the treatment of aGC at The James Cancer Hospital between January 1, 2021, and May 31, 2024. The coprimary end points were progression-free survival (PFS) and overall survival at 6 months and the incidence of select grade 3 or 4 adverse events (neutropenia, thrombocytopenia, diarrhea, pulmonary adverse events, or any hospitalization for a potentially drug-related adverse event).
RESULTS: A total of 14 patients met the study criteria, of whom 13 were evaluable for survival. TDxd was administered in the second-line setting in 5 patients, and the median number of previous therapies for the entire cohort was 2. The median average TDxd dose per patient was 6.4 mg/kg, and the median relative dose intensity was 89.9%. The 6-month PFS rate was 46.2% (n=6) and the 6-month overall survival rate was 61.5% (n=8). Of the 10 patients evaluable for disease response, 7 had at least a partial response according to their primary oncologist. Of the 14 total patients, 7 (50%) had a grade 3 or 4 adverse event that was considered potentially treatment-related, including 2 (14.3%) cases of fatal lung adverse events. A total of 6 patients discontinued TDxd because of adverse events without disease progression and an additional patient had radiographic progression but continued receiving TDxd treatment, which was later stopped because of worsening adverse events.
CONCLUSION: Despite use in a heavily pretreated sample, TDxd was administered with high relative dose intensity, and the efficacy outcomes were comparable with those in larger controlled clinical trials. The adverse events were worse in our cohort, however, compared with clinical trials. It is possible that use of a lower TDxd dose would improve tolerability without compromising efficacy.
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