Kadcyla After Breast Cancer Surgery: Long-Term Survival Benefit Confirmed

HER2-positive breast cancer accounts for 15-20% of all breast cancers. Although it generally follows a more aggressive course, targeted treatments have made effective treatment possible. Most patients with HER2-positive breast cancer are diagnosed at an early stage and treated successfully with preoperative targeted drugs, chemotherapy and surgery. However, for patients with residual disease after surgery and a high risk of recurrence, improving adjuvant treatment options is critically important. The two main targeted treatments currently approved for this purpose and also used in Türkiye are trastuzumab (Herceptin and its biosimilars) and T-DM1 (Kadcyla). Kadcyla previously received FDA (US Food and Drug Administration) approval on the basis of the phase III KATHERINE trial. Its long-term findings were published on 15 January 2025 in NEJM . The study showed that adjuvant ado-trastuzumab emtansine (T-DM1) was superior to trastuzumab after surgery and improved survival rates in this patient population.

What Is T-DM1?

T-DM1 is an antibody-drug conjugate combining trastuzumab with the chemotherapy drug emtansine. Trastuzumab binds to the HER2 receptor on cancer cells, allowing emtansine to enter the cells more effectively and destroy them from within.

The three-year KATHERINE trial data published in 2019 showed that, following neoadjuvant treatment , adjuvant T-DM1 reduced the risk of death or cancer recurrence by 50% in patients with HER2-positive early breast cancer who had residual disease.

Details of the KATHERINE Trial

Investigators enrolled 1,486 patients with HER2-positive early breast cancer and residual invasive disease in the breast or axillary lymph nodes after neoadjuvant treatment. Following taxane-based chemotherapy, HER2-targeted trastuzumab and surgical tumor removal, patients were randomly assigned to receive either standard adjuvant trastuzumab or adjuvant T-DM1.

Key Findings

• Risk of Death and Disease: Adjuvant T-DM1 reduced the risk of death or invasive disease by 46% compared with trastuzumab.

• 7-Year Survival Rates:

  • Invasive disease-free survival in the T-DM1 group was 80.8%.

  • Invasive disease-free survival in the trastuzumab group was 67.1%.

  • Overall survival rates were 89.1% in the T-DM1 group and 84.4% in the trastuzumab group.

• Side Effects: Grade 3 or higher adverse events occurred in 26.1% of the adjuvant T-DM1 group, compared with 15.7% of the trastuzumab group. However, the overall safety profile was considered acceptable.

The benefit of adjuvant T-DM1 was emphasized as consistent across subgroups defined by disease extent, hormone receptor status, neoadjuvant treatment regimen, pathological lymph node status after surgery, age and race.

Commentary

Following advances in treatments for HER2-positive breast cancer has been both exciting and encouraging for me. Since HER2 gene amplification was identified as a targetable oncogene, the drugs developed have established new standards of care for this disease, demonstrating how groundbreaking scientific research can be. Long-term findings on T-DM1 for HER2-positive early breast cancer show that the drug not only improves invasive disease-free survival but also significantly increases overall survival rates.

KATHERINE demonstrated that T-DM1 went beyond trastuzumab treatment to provide substantially greater efficacy. Earlier reporting of the results has again highlighted how effective this treatment is. Long-term follow-up findings also confirmed that T-DM1 provides lasting benefits beyond invasive disease-free survival in HER2-positive early breast cancer.

More effective treatment options are currently being sought for patients with low HER2 expression who do not respond adequately to T-DM1. In this context, investigating next-generation antibody-drug candidates such as trastuzumab deruxtecan (Enhertu) may open the door to even more promising treatment approaches in the future.