Low-dose vs. standard-dose trastuzumab deruxtecan in north Indian patients: Balancing efficacy, toxicity, and cost.

Abstract

e13028 Background: The median target exposure level of trastuzumab deruxtecan (TDxD) with standard dose is approximately 2.5 times higher than the derived from pre-clinical studies and a wide range of drug levels have shown efficacy most likely because of bystander effect. Toxicities are substantial with conventional standard dosage. We report our real-world experience with low dose TDxD aimed at in improving access by reducing cost and adverse effects. Methods: This is two center retrospective study from north India of prospectively maintained data from Jul 2024 to Dec 2025. All consecutive patients who received ≥1 dose of TDxD were included and either received either 2.7mg/kg (LD) or 5.4 mg/kg (SD) every 3 weeks. Overall response rate (ORR = Complete remission + partial remission) and Central nervous system response rate (CNS) were primary objectives as given the recent availability of TDxD and survival data needing longer follow up. Results: 30 women with various cancers, breast cancer being most common (23/30) received TDxD. 85% of patients received TDxD in third or later line. 25 patients received LD. HER2 status and other clinical characteristics are summarized in Table. Response evaluation was available for 18 patients. ORR was 77% and CNS response rate was 66% (4/6). The ORR did not differ in LD versus SD dose cohorts (p = 0.16). Treatment was well tolerated and only one patient had grade 1 lung toxicity. She received SBRT to two lesions prior to TDxD. One patient experienced grade 4 diarrhea. Conclusions: Low-dose at 2.7 mg/kg q 3weeks is as efficacious as standard dose, including CNS RR. Large randomized prospective studies are warranted. Clinical Characteristics (n=30). Clinical variables Values Frequency (%) Age Median 42 years(range:28-70) Gender Female 100 Weight Mean 60kg (range:38-84) Cancer subtype Breast Gallbladder Colon Gastric ^ CUP (NGS-Her2neu amplified) 232111 766333 Disease stage 4 100 Her2neu status (n=29) IHC3+, IHC2+/FISH+ve IHC2+/FISH+ve, IHC1+ IHC+<1 1793 583310 Brain metastases before ** TDxD initiation (n=27) Yes 12 44 Prior Line of therapies 1 2 3 4>=5 259104 616303313 Prior # TDM1 (eligible n=20) Yes 8 44 Dose used (q3weeks) ## LD 2.7mg/kg SD 5.4mg/kg 255 8317 *IHC: Immunohistochemistry, ** TDxD: Trastuzumab deruxtecan, # TDM1: Trastuzumab ado emtansine, ## LD: low dose, SD: standard dose, ^ CUP: Carcinoma of Unknown primary.