Cheplapharm — Xeloda EMA EPAR variation assessment report (EMEA/H/C/000316, 2001)
Cheplapharm · 2001 · EMA EPAR variation assessment report
Report summary
This report assesses a variation application for Xeloda (capecitabine) to expand its metastatic colorectal cancer (mCRC) indication to include combination therapy at any treatment line. Two pivotal Phase III non-inferiority trials (NO16966, NO16967) compared XELOX (capecitabine + oxaliplatin) with FOLFOX-4 (5-FU/LV + oxaliplatin). While investigator assessment supported non-inferiority in progression-free survival (PFS) for XELOX, independent review committee assessment was inconsistent. XELOX demonstrated non-inferiority to FOLFOX-4 in PFS and overall survival (OS) for both first and second-line mCRC. Safety profiles were comparable overall, though XELOX had lower hematological toxicities but higher gastrointestinal disorders and hand-foot syndrome. The CHMP accepted the Type II variation, with the Marketing Authorisation Holder committing to a revised Risk Management Plan, a diagnostic biomarker report, and a pharmacogenetic substudy report.
Key findings — cited to the page
| Incidence of grade 3/4 neutropenia/granulocytopenia in FOLFOX-4 group | 43.8 % | NO169662 · p.18 |
| Incidence of all grade infections in XELOX group | 32.2 % | NO169662 · p.18 |
| Incidence of grade 3/4 haematological AEs in FOLFOX-4 group | 49.3 % | NO169662 · p.17 |
| Incidence of grade 3/4 neutropenia/granulocytopenia in XELOX group | 7.0 % | NO169662 · p.18 |
| Incidence of grade 3/4 febrile neutropenia in XELOX group | 0.9 % | NO169662 · p.18 |
| Incidence of grade 3/4 febrile neutropenia in FOLFOX-4 group | 4.8 % | NO169662 · p.18 |
| Incidence of grade 4 AEs in FOLFOX-4 group | 24.8 % | NO169662 · p.17 |
| Incidence of grade 3/4 haematological AEs in XELOX group | 15.9 % | NO169662 · p.17 |
| Incidence of grade 4 haematological AEs in XELOX group | 2.1 % | NO169662 · p.17 |
| Incidence of grade 4 haematological AEs in FOLFOX-4 group | 19.1 % | NO169662 · p.17 |
| Incidence of grade 4 AEs in XELOX group | 12.4 % | NO169662 · p.17 |
| Incidence of all grade infections in FOLFOX-4 group | 45 % | NO169662 · p.18 |
Source: Cheplapharm ↗ · 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 →