HER2-positive breast cancer is a biologically distinct subtype characterized by amplification of the ERBB2 gene and overexpression of the HER2 protein, leading to activation of oncogenic signaling pathways and aggressive tumor behavior.1–3 This phenotype accounts for approximately 19% of invasive breast cancers globally. Historically, before HER2-targeted therapy became standard, patients experienced 10-year recurrence rates of 30% to 50% and lower 5-year survival rates (85.7% for hormone receptor [HR]–negative/HER2-positive and 91.5% for HR-positive/HER2-positive) compared with the higher survival rates seen in HER2-negative disease.4 Survival outcomes in both early and advanced HER2-positive disease have improved following the introduction of targeted therapies, beginning with trastuzumab (FDA approved in September 1998) and later including pertuzumab and antibody-drug conjugates.5,6 Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate that links trastuzumab to the cytotoxic agent DM1 via a stable linker, enabling targeted delivery of chemotherapy to HER2-expressing tumor cells while retaining trastuzumab’s anti-HER2 effects.7

Breast cancer is a major global health concern, with more than 2.3 million new cases and 685 000 deaths reported in 2020, accounting for nearly 1 in 4 cancer diagnoses among women.8 In India, breast cancer has surpassed cervical cancer as the leading malignancy among women, with an estimated age-standardized incidence rate of 25.8 per 100 000 and a significant proportion of cases presenting at locally advanced stages. The prevalence of HER2 positivity in Indian breast cancer cohorts is comparable to global rates, typically ranging between 18% and 25%.9,10 However, the burden of late-stage presentation, limited screening, variability in access to HER2 testing, and high treatment costs pose unique challenges in delivering guideline-based care in low- and middle-income countries (LMICs). Cost remains a major barrier to the adoption of advanced HER2-targeted agents, particularly innovator T-DM1, in Indian oncology practice.11,12

The current standard for patients with residual invasive HER2-positive disease after neoadjuvant chemotherapy is adjuvant T-DM1, as established by the phase 3 KATHERINE trial, which demonstrated a 50% reduction in the risk of invasive disease recurrence or death compared with trastuzumab alone, with 3-year invasive disease-free survival (iDFS) rates of 88.3% vs 77.0%.4,13–15 Despite its efficacy, the high acquisition cost of innovator T-DM1 limits its accessibility in LMICs, often resulting in suboptimal treatment sequencing. Biosimilar formulations offer a cost-effective alternative and have demonstrated comparable efficacy and safety in metastatic HER2-positive breast cancer.16 This retrospective single-center study was designed to evaluate the efficacy, measured by iDFS, and safety profile of Ujvira (Zydus Lifesciences), a trastuzumab emtansine biosimilar, in patients with high-risk early-stage HER2-positive breast cancer in India. The study aimed to address a critical gap in locally relevant evidence and support equitable access to effective therapy.

This single-center retrospective study provides early real-world evidence for a trastuzumab emtansine (T-DM1) biosimilar as adjuvant therapy in Indian women with stage II or III HER2-positive breast cancer and residual disease after neoadjuvant therapy. The 12-month iDFS rate was 79.2%; given the short follow-up and the small number of events (n=5), median iDFS was not reported. In KATHERINE, adjuvant T-DM1 reduced the risk of invasive recurrence or death by 46% compared with trastuzumab alone; 7-year iDFS was 80.8% with T-DM1 vs 67.1% with trastuzumab, and overall survival also improved.17 In the present cohort, 20.8% of patients relapsed, usually to bone, brain, or liver, and no deaths occurred during 14 months of follow-up. The observed relapse rate likely reflects the higher baseline risk profile of the cohort, including a predominance of stage III disease and the presence of comorbidities. Longer follow-up is needed to assess whether these early outcomes converge with those of the KATHERINE population.

The ATEMPT phase 2 trial explored T-DM1 in lower-risk stage I disease. After 5.8 years of follow-up, patients receiving T-DM1 had a 5-year iDFS of 97%, with only 5 recurrences, and a toxicity profile distinct from paclitaxel plus trastuzumab. These results, together with outcomes from the APT trial, demonstrate that excellent long-term disease control is achievable in patients with small, node-negative HER2-positive tumors.18

The present cohort, however, consisted of patients with residual invasive disease after neoadjuvant chemotherapy, a population with substantially higher recurrence risk. In this setting, adjuvant T-DM1 is supported by the KATHERINE trial and remains the only therapy with proven benefit in improving iDFS.17 Trials such as KAITLIN and KRISTINE, which evaluated T-DM1 plus pertuzumab in place of standard taxane-based regimens, did not demonstrate improved outcomes, suggesting that T-DM1 should be reserved for patients with residual disease following neoadjuvant therapy.

In metastatic disease, the EMILIA and TH3RESA trials demonstrated improvements in progression-free and overall survival with T-DM1 compared with lapatinib plus capecitabine and physician’s choice chemotherapy, respectively.19 These findings, together with data from the KAMILLA safety study, established the manageable toxicity profile of T-DM1, including thrombocytopenia and transaminase elevations.20 The current real-world findings are consistent with these reports: thrombocytopenia, neutropenia, and anemia were common but predominantly grade 1 or 2, and declines in LVEF were asymptomatic.

A strength of this study is the exploration of potential prognostic factors beyond the primary end point. Exploratory analyses demonstrated numerically longer iDFS in patients with stage III disease and those undergoing mastectomy; however, these findings were counterintuitive. These observations likely reflect selection bias and limited statistical power, as only 5 patients had stage II disease. Patients initiating treatment at higher starting doses demonstrated numerically longer iDFS, although dose selection was influenced by clinical factors and vial-based rounding, limiting interpretability.

Hormone receptor status, ECOG performance status, and menopausal status did not show a meaningful association with iDFS. Socioeconomic factors showed trends: patients paying out of pocket had numerically longer iDFS than those with insurance. While not statistically significant, this observation highlights the potential impact of affordability and adherence. High out-of-pocket costs can adversely affect treatment persistence. A US cross-sectional study demonstrated reduced adherence to aromatase inhibitors with increasing copayments, and similar patterns have been reported for oral chemotherapy.21,22

In India, breast cancer treatment costs impose substantial financial burden. A retrospective study from Tata Memorial Centre estimated mean total treatment costs of ₹258 095 ($3531), with out-of-pocket expenditure accounting for the majority.22 Financial toxicity may therefore contribute to dose delays or early discontinuation, potentially compromising outcomes.

Biosimilars offer an opportunity to improve access to HER2-targeted therapies by reducing costs. Real-world studies have demonstrated comparable efficacy and safety of trastuzumab biosimilars relative to the originator, with significant cost savings.23 Our findings support the feasibility of delivering a T-DM1 biosimilar in a resource-constrained setting with acceptable safety and disease control. The median progression-free survival reported in an Indian retrospective study of a T-DM1 biosimilar in metastatic breast cancer is comparable to outcomes observed here, further supporting biosimilar use across disease stages.24

The study has important limitations, including its retrospective design, small sample size, single-center setting, short follow-up, and lack of a comparator arm. These factors limit generalizability and preclude adjusted analyses. Despite these limitations, this study contributes to the limited real-world literature on T-DM1 biosimilars in early-stage HER2-positive breast cancer. Future multicenter studies with larger cohorts, longer follow-up, and incorporation of patient-reported outcomes are needed to confirm these findings and evaluate long-term effectiveness and economic impact.

This retrospective real-world evaluation suggests that adjuvant trastuzumab emtansine biosimilar use in patients with high-risk early-stage HER2-positive breast cancer is feasible and associated with a manageable safety profile consistent with previously reported clinical trials and real-world data. Given the small sample size, short follow-up, and descriptive nature of this analysis, efficacy outcomes should be interpreted cautiously. Larger multicenter studies with longer follow-up, incorporation of patient-reported outcomes, and formal cost-effectiveness analyses are required to confirm these findings and to inform equitable implementation of biosimilar-based therapies in low- and middle-income countries.