Biosimilar Trastuzumab Emtansine Shows Consistent PFS in HER2-Positive Breast Cancer

Access to antibody-drug conjugates remains uneven in many low- and middle-income countries, leaving clinicians to balance evidence-based care with financial realities.1 In that context, new real-world data from India evaluated whether a trastuzumab emtansine biosimilar could deliver outcomes comparable to the reference product for patients with HER2-positive metastatic breast cancer.2

In a retrospective, single-center analysis published in Cureus, Chandrakanth and colleagues assessed the safety and effectiveness of Ujvira (ZRC-3256), a biosimilar to trastuzumab emtansine (T-DM1), in 51 patients treated at a tertiary oncology center in India. The reference product, Kadcyla, had previously demonstrated improved progression-free survival (PFS) and overall survival in phase 3 trials such as EMILIA and TH3RESA. However, high acquisition costs limited its availability in many resource-constrained settings, prompting interest in lower-cost biosimilar alternatives.

All patients in the current cohort had HER2-positive metastatic breast cancer and prior exposure to trastuzumab. Ujvira was administered intravenously at 3.6 mg/kg every 21 days until disease progression or unacceptable toxicity. The primary end point was PFS, estimated using the Kaplan-Meier method. Secondary end points included objective response rate (ORR), safety as graded by CTCAE version 5.0, and exploratory subgroup analyses based on clinical and biomarker characteristics.

The mean (SD) age of participants was 58.0 (8.4) years, and 49.0% were 60 years or older. Most patients were postmenopausal (92.2%) and had an Eastern Cooperative Oncology Group performance status of 1 (64.7%). Comorbidity burden was notable: 60.8% had hypertension, and 58.8% had type 2 diabetes. More than 40% had at least 3 metastatic sites at baseline. HR-positive disease was common, with estrogen receptor positivity in 70.6% and progesterone receptor positivity in 54.9%. Nearly three-quarters (74.5%) had HER2 immunohistochemistry 3+ tumors, and 23.5% were fluorescence in situ hybridization–positive.

Patients were heavily pretreated. All had received prior trastuzumab; 84.3% had prior taxane exposure, 62.7% anthracyclines, 39.2% lapatinib, and 19.6% pertuzumab. Forty patients (78.4%) received Ujvira in the second-line setting, and 11 (21.6%) in the third-line setting.

Median PFS for the overall cohort was 6.9 months (95% CI, 6.2-9.0). In second-line use, median PFS was 7.7 months (95% CI, 6.2-10.5), compared with 9.1 months (95% CI, 1.47-not estimable) in the third-line setting; the difference was not statistically significant (P = .9335). The ORR was 35.3%.

Exploratory subgroup analyses showed numerical but not statistically significant differences across clinical characteristics. Patients with brain metastases had a median PFS of 6.3 months compared with 9.1 months in those without central nervous system involvement (P = .2203). Patients with diabetes had a median PFS of 7.0 months vs 9.37 months among those without diabetes (P = .2405). Progesterone receptor–positive tumors were associated with numerically longer PFS (9.37 vs 7.7 months), although this did not reach statistical significance.

Treatment was generally well tolerated. The most common adverse events of any grade were thrombocytopenia (33.3%), anemia (19.6%), and neutropenia (7.8%). Elevated transaminases occurred in 3.9% of patients and represented the only reported grade 3 or higher toxicity. Reduced left ventricular ejection fraction below 50% was observed in 3.9% of patients. Dose reductions were required in 15.7% of patients because of treatment-related toxicities. Median PFS was similar among those who required dose reductions and those who did not (6.8 vs 6.9 months; P = .25), suggesting that dose modification did not appear to compromise effectiveness.

When contextualized against registrational trials of the reference product, the observed median PFS was shorter than the 9.6 months reported in the EMILIA study. The authors attributed this difference to the real-world nature of the cohort, including substantial comorbidity burden and prior exposure to multiple HER2-directed therapies. They also noted alignment with other real-world studies of T-DM1 that reported median PFS of approximately 6 months.

The study had several limitations. Its retrospective, single-center design introduced the potential for selection and reporting bias. The sample size was modest, limiting statistical power for subgroup comparisons and increasing the risk of type II error. Overall survival data were immature at the time of analysis, precluding robust comparisons with global benchmarks. Additionally, 2 authors were affiliated with the biosimilar’s manufacturer, although they reported limited roles in study conceptualization and manuscript review.

Despite these constraints, the findings add to the growing body of real-world biosimilar evidence in oncology. For managed care stakeholders in resource-limited settings, the data suggest that trastuzumab emtansine biosimilars may provide clinically meaningful disease control with a safety profile consistent with prior experience, even among heavily pretreated and comorbid patient populations.

References

1. Montemurro F, Delaloge S, Barrios CH, et al. Trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer and brain metastases: exploratory final analysis of cohort 1 from KAMILLA, a single-arm phase IIIb clinical trial. Ann Oncol. 2020;31(10):1350-1358. doi:10.1016/j.annonc.2020.06.020
2. Chandrakanth MV, Agarwala V, Manna R, et al. Real-world evaluation of a trastuzumab emtansine biosimilar (Ujvira) in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. Cureus. Published online February 16, 2026. doi:10.7759/cureus.103700