Boehringer Ingelheim — Giotrif EMA EPAR public assessment report (EMEA/H/C/002280, 2013)
Boehringer Ingelheim · 2013 · EMA EPAR public assessment report
Report summary
This report summarizes the EMA's assessment of Giotrif (afatinib) for EGFR-mutated non-small cell lung cancer (NSCLC). Afatinib, an irreversible ErbB family inhibitor, demonstrated potent activity against various EGFR mutations, including those resistant to first-generation inhibitors, in non-clinical studies and tumor xenograft models. Pharmacokinetic studies detailed absorption, distribution, and metabolism. Non-clinical safety assessments covered repeat-dose toxicity, genotoxicity, reproductive toxicity, and ecotoxicity. Clinical trials (LUX Lung 3, LUX Lung 6) showed significant progression-free survival benefits in EGFR-mutated NSCLC patients. However, safety concerns included high rates of grade 3+ adverse events (diarrhea, rash, stomatitis) and serious risks like ILD and hepatic impairment. The CHMP recommended marketing authorization for EGFR TKI-naïve adult patients with activating EGFR mutations, but excluded those with secondary resistance to erlotinib/gefitinib due to insufficient evidence. A pharmacovigilance plan was established to monitor safety.
Key findings — cited to the page
| incidence of grade CTCAE 3 or higher AEs | 60.7 % | · p.116 |
| Any AE ≥Grade 3 (afatinib, LUX-Lung 3) | 60.7 % | · p.119 |
| worst grade 3 or above lymphocytes (afatinib, SAF-1) | 8.4 % | · p.114 |
| worst grade 3 or above lymphocytes (chemotherapy) | 10.2 % | · p.114 |
| Grade 2 ALT elevations | 8 % | · p.118 |
| Grade 3 ALT elevations | 4 % | · p.118 |
| worst on-treatment haemoglobin value of grade 3 or above (afatinib, SAF-1) | 2.7 % | · p.113 |
| worst on-treatment haemoglobin value of grade 3 or above (afatinib, SAF-3) | 1.8 % | · p.113 |
| worst grade 3 or above lymphocytes (afatinib, SAF-3) | 6.8 % | · p.114 |
| worst grade 3 or above lymphocytes (placebo) | 4.7 % | · p.114 |
| CTCAE Grade ≥ 3 ILD-like adverse reactions | 0.5 % | · p.118 |
| Any AE ≥Grade 3 (afatinib, LUX-Lung 6) | 46.9 % | · p.119 |
Source: Boehringer Ingelheim ↗ · 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 →