Roche Holding AG — Kadcyla EMA EPAR variation assessment report (EMEA/H/C/002389, 2013)
Roche Holding AG · 2013 · EMA EPAR variation assessment report · company profile →
Report summary
This report summarizes the EMA's assessment of Roche's Type II variation for Kadcyla (trastuzumab emtansine), seeking to extend its indication for adjuvant treatment of HER2-positive early breast cancer with residual invasive disease post-neoadjuvant therapy. The application is supported by the Phase III KATHERINE study, which compared Kadcyla to trastuzumab. KATHERINE demonstrated a statistically significant improvement in invasive disease-free survival (IDFS) for Kadcyla (HR 0.50), despite immature overall survival data. However, Kadcyla was associated with higher rates of adverse events, including thrombocytopenia, hepatotoxicity, and peripheral neuropathy, leading to more discontinuations. Despite these safety concerns, the clinical benefit in reducing recurrence was deemed to outweigh the risks, leading to a recommendation for the indication extension.
Key findings — cited to the page
| patients with Grade ≥3 AE in hemorrhage category (trastuzumab) | 0.3 % | · p.73 |
| Increased transaminases (AST/ALT) (all grades) | 32.4 % | · p.77 |
| most common NCI-CTCAE Grade >=3 ADRs with trastuzumab emtansine (>2%) | thrombocytopenia, increased transaminases, anaemia, neutropenia, fatigue and hypokalaemia | · p.69 |
| NODULAR REGENERATIVE HYPERPLASIA (Grade 3) (trastuzumab emtansine) | 0.3 % | KATHERINE · p.78 |
| Left ventricular dysfunction (all grades) | 3.0 % | · p.76 |
| Left ventricular dysfunction (Grade 3 or 4) | 0.5 % | · p.76 |
| Grade 3 hypersensitivity SAE in ADA+ and NAb+ patient | 1 | KATHERINE · p.62 |
| most common NCI-CTCAE Grade 3 or 4 ADRs with Kadcyla (>2%) | thrombocytopenia, fatigue, increased transaminases, anaemia, hypokalaemia, musculoskeletal pain and neutropenia | · p.62 |
| Thrombocytopenia (all grades) | 28.5 % | · p.72 |
| Thrombocytopenia (Grade ≥ 3) | 5.7 % | · p.72 |
| patients with Grade ≥3 AE in hemorrhage category (trastuzumab emtansine) | 0.4 % | · p.73 |
| Increased transaminases (Grade 3 and 4) | 1.5 % | · p.77 |
Source: Roche Holding AG ↗ · License: EMA - reuse permitted with acknowledgement. Summary and findings are extracted from the published document; every figure cites its page. Informational only — not investment advice. Explore the Oncology library →