What does this research mean for the field?

Low-dose trastuzumab deruxtecan (2.7 mg/kg) is as efficacious as the standard dose (5.4 mg/kg) in patients with advanced cancers, including central nervous system responses, with a manageable toxicity profile. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This study evaluates the efficacy and safety of low-dose trastuzumab deruxtecan compared to standard-dose in patients with various cancers.

May 30, 2026

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

Key Points

This study evaluates the efficacy and safety of low-dose trastuzumab deruxtecan compared to standard-dose in patients with various cancers.
Retrospective data from two centers in North India from July 2024 to December 2025.
Included patients who received ≥1 dose of trastuzumab deruxtecan at either 2.7 mg/kg (low-dose) or 5.4 mg/kg (standard-dose).
Evaluated overall response rate (ORR) and central nervous system response rate (CNS RR) as primary objectives.
Of 30 women treated, the overall response rate (ORR) was 77%, with 66% CNS response rate among those assessed.
Response rates did not significantly differ between low-dose and standard-dose groups (p = 0.16).
Treatment was well tolerated, with only one case of grade 1 lung toxicity and one case of grade 4 diarrhea.

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+=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.

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Cite This Study

Ahlawat et al. (Thu,) studied this question.

synapsesocial.com/papers/6a1a80c00307b78509432a87 https://doi.org/https://doi.org/10.1200/jco.2026.44.16_suppl.e13028

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