Regulatory Decision Summary for Kadcyla

Review decision

The Regulatory Decision Summary explains Health Canada’s decision for the product seeking market authorization. The Regulatory Decision Summary includes the purpose of the submission and the reason for the decision.


Product type:

Drug

Medicinal ingredient(s):

trastuzumab emtansine

Therapeutic area:

Antineoplastic agent

Type of submission:

Supplemental New Drug Submission (SNDS)

Control number:

227372
What was the purpose of this submission?

 

The purpose of this submission was to seek authorization for expansion of the Kadcyla monotherapy indication for the adjuvant treatment of HER2-positive early breast cancer patients who have residual disease. The indication authorized for Kadcyla monotherapy is for the adjuvant treatment of HER2-positive early breast cancer patients who have residual invasive disease following neoadjuvant taxane and trastuzumab-based treatment.

 

Why was the decision issued?

 

Authorization was based on the results of a single pivotal Phase III open-label adjuvant study of 1486 patients with HER2-positive, early breast cancer (EBC) with residual invasive tumour in the breast and/or axillary lymph nodes following neoadjuvant taxane and trastuzumab-based therapy. The HER2-positive EBC patients were randomized 1:1 to receive treatment with either Kadcyla monotherapy (n=743) or trastuzumab monotherapy (n=743).

The EBC patients treated with adjuvant Kadcyla monotherapy for up to 14 cycles had a statistically significant improvement in invasive disease-free survival (IDFS) compared to patients treated with adjuvant trastuzumab monotherapy for up to 14 cycles, corresponding to a 50% reduction in risk of an IDFS event. This surrogate endpoint was considered clinically meaningful based on the magnitude of the benefit observed (hazard ratio = 0.50) and correlation reported between disease-free survival and overall survival in the early breast cancer setting. A consistent benefit in IDFS for Kadcyla over trastuzumab was seen in all the pre-specified subgroups evaluated, supporting the robustness of the overall results. The primary IDFS analysis was also supported by other secondary outcome measures tested.

The safety of adjuvant Kadcyla was generally well-tolerated in early breast cancer patients. More patients treated with Kadcyla (18%) compared with trastuzumab (2%) discontinued therapy due to adverse events prior to completing 14 cycles of therapy. While no new major adverse events for Kadcyla monotherapy were reported in this setting, the Product Monograph was updated to report on the increase in incidence and severity of thrombocytopenia for early breast cancer patients of Asian descent compared to non Asian patients. The Product Monograph was also updated to document that Kadcyla monotherapy may exacerbate radiation pneumonitis reported in early breast cancer patients who receive adjuvant radiotherapy.

Based on the totality of the data, the benefit-risk profile was considered positive. A Notice of Compliance was recommended to expand the indication of Kadcyla monotherapy for the adjuvant treatment of HER2-positive early breast cancer patients who have residual invasive disease following neoadjuvant taxane and trastuzumab-based treatment.

 

Decision issued

Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations.