Roche's ADC Drug Kadcyla® Approved in China for Adjuvant Treatment of HER2-Positive Early Breast Cancer

Roche Pharma China Announces Formal Approval of Innovative Targeted Drug Herceptin by the National Medical Products Administration^®(English brand name: Kadcyla^®, generic name: trastuzumab emtansine), is indicated as monotherapy for the adjuvant treatment of patients with HER2-positive early breast cancer who have residual invasive disease after receiving neoadjuvant therapy based on a taxane combined with trastuzumab. As the first antibody-drug conjugate (ADC) approved globally for monotherapy in solid tumors, and also the first HER2-targeted ADC product in China, Kadcyla^®The approval enriches the options for intensified adjuvant therapy in patients with HER2-positive breast cancer who have residual disease after neoadjuvant therapy and surgery, bringing these high-risk patients closer to a cure.

Striving for Excellence on the Path to Curing Early-Stage Breast Cancer: A Novel Mechanism of Action Facilitates Clinical Breakthroughs

This time, Herceptin^®The approval was based on the KATHERINE study, which is the first global, multicenter, Phase III pivotal registration clinical study to optimize adjuvant therapy in patients with HER2-positive breast cancer who have residual disease after neoadjuvant therapy. Although Herceptin^®The market launch of (trastuzumab) and Perjeta® (pertuzumab) has changed the clinical outcomes for patients with HER2-positive breast cancer, but the use of Herceptin in adjuvant therapy for patients with early-stage HER2-positive breast cancer^®(Trastuzumab), approximately 25% of patients with HER2-positive early breast cancer still experience recurrence and metastasis after 10 years. Meanwhile, the use of Herceptin in neoadjuvant therapy^®(Trastuzumab) + Perjeta^®(Pertuzumab) After dual-target therapy, approximately 40-60% of patients still do not achieve pCR. These patients who fail to achieve pCR after neoadjuvant therapy have a higher risk of recurrence within five years compared to those who achieve pCR, with some risks approaching nearly 80%. Herceptin^®(Trastuzumab deruxtecan) also brings hope to this patient population.

The KATHERINE study showed that Herceptin^®In the trastuzumab emtansine (T-DM1) group, the 3-year invasive disease-free survival (iDFS) rate after adjuvant therapy was 88.3%, compared with 77% in the trastuzumab monotherapy group, representing an absolute difference of 11.3% (HR: 0.5; 95% CI: 0.39–0.64; P < 0.001). Furthermore, the KATHERINE study confirmed that following T-DM1 treatment, the hazard ratio (HR) was 0.6 regardless of estrogen receptor (ER) status (positive or negative), resectability, minimal residual tumor burden, tumor size <1 cm, or node-negative status. This indicates that for patients with HER2-positive breast cancer who have residual disease after neoadjuvant therapy and surgery, treatment with trastuzumab emtansine can further reduce the risk of disease recurrence and death by 50%.

Herzuma^®The remarkable efficacy of trastuzumab emtansine in clinical treatment is closely attributed to its innovative mechanism of action. Kadcyla® (trastuzumab emtansine) is a stable antibody-drug conjugate (ADC) formed by linking Herceptin® (trastuzumab), a classic anti-HER2 targeted therapy, with the microtubule-inhibiting chemotherapeutic agent maytansine via a thioether linker. Characterized by its ability to selectively kill tumor cells, it is also known as a “biological missile.” Kadcyla® (trastuzumab emtansine) directly delivers potent chemotherapy to HER2-positive cancer cells, thereby maximizing the efficacy of targeted therapy while exerting cytotoxic effects, and simultaneously sparing healthy tissues from damage.

High Risk of Recurrence Persists in Early-Stage Breast Cancer Patients: New Drugs Bring New Decision Points for Subsequent Treatment

Currently, in the treatment of HER2-positive early-stage breast cancer, both preoperative neoadjuvant therapy and postoperative adjuvant therapy are integral components of comprehensive management for early-stage tumors. The goal of treating early-stage breast cancer is to provide patients with the best chance of cure. The objectives of neoadjuvant therapy for breast cancer are not only to downstage inoperable breast cancer to operable disease and to convert cases ineligible for breast-conserving surgery into candidates for such procedures, but also to obtain in vivo information on drug sensitivity, thereby guiding subsequent treatment to improve long-term patient survival. The KATHERINE study demonstrated that in patients with residual disease after neoadjuvant therapy and surgery, the use of Kadcyla® (trastuzumab emtansine) in the adjuvant setting reduces the risk of cancer recurrence or death by 50%. Therefore, whether patients achieve pathological complete response (pCR) after neoadjuvant therapy will serve as a key decision point for future individualized adjuvant treatment strategies.

According to the Neosphere study, compared with Herceptin monotherapy^®Compared with (trastuzumab) therapy, Perjeta® (pertuzumab) in combination with Herceptin^®(Neoadjuvant anti-HER2 therapy with trastuzumab) can improve the pathological complete response (pCR) rate in high-risk patients, but 60% of patients still fail to achieve pathological complete response (pCR) after neoadjuvant therapy.

Continuous Innovation in Drug Development: Gradually Covering the Entire Disease Course of Breast Cancer

In the field of HER2-positive breast cancer treatment, Roche has established a comprehensive anti-HER2 therapy system covering neoadjuvant therapy, postoperative adjuvant therapy, and first-line treatment for advanced disease, enabling an increasing number of Chinese patients to benefit from these treatments.

In addition to HER2-positive breast cancer, Roche has also made progress in the treatment of triple-negative breast cancer, one of the most aggressive types of breast cancer. Its anti-PD-L1 tumor immunotherapy drug, Tecentriq^®(Atezolizumab), as the first tumor immunotherapy drug approved by the FDA for the treatment of triple-negative breast cancer. Tecentriq® can bind to the PD-L1 ligand protein expressed on tumor cells and tumor-infiltrating immune cells, blocking its interaction with PD-1 and B7.1 receptors. By blocking the PD-L1 pathway, Tecentriq^®It can effectively activate T cells.

Regarding the KATHERINE Study

The KATHERINE study included a total of 1,486 patients who received trastuzumab-containing regimens during neoadjuvant therapy^®(Trastuzumab) Trastuzumab and taxane chemotherapy for patients with HER2-positive early breast cancer who have residual disease after surgery. After randomization, patients received either trastuzumab emtansine at 3.6 mg/kg or Herceptin.^®(Trastuzumab) Trastuzumab 6 mg/kg, administered once every 3 weeks, for a total of 14 cycles.