Cheplapharm — Tarceva EMA EPAR variation assessment report (EMEA/H/C/000618, 2005)
Cheplapharm · 2005 · EMA EPAR variation assessment report
Report summary
This report summarizes a Type II variation application for Tarceva (erlotinib) by Roche, addressing its use in NSCLC patients without EGFR-activating mutations after prior chemotherapy. Following concerns from the IUNO study, the SmPC wording was revised to reflect efficacy uncertainties in this population. The report details efficacy and safety data from numerous trials (BR.21, TAILOR, TITAN, DELTA, PROSE, HORG, LUX-Lung 8, TRUST, PEPiTA), comparing erlotinib to chemotherapy in second-line advanced NSCLC, primarily in EGFR wild-type patients. While BR.21 showed a modest benefit, many studies and meta-analyses indicated no significant overall survival advantage for erlotinib over chemotherapy, with some showing better PFS for chemotherapy. Real-world data also suggested comparable or slightly worse outcomes for erlotinib. Erlotinib's safety profile is generally manageable, with common adverse events like rash and diarrhea, and fewer severe myelosuppression events than chemotherapy. Preclinical evidence supports erlotinib's activity in wild-type EGFR tumors, and post-hoc analyses of BR.21 explored EGFR expression and prior chemotherapy response.
Key findings — cited to the page
| Grade 1 or 2 diarrhoea (placebo) | 17 % | BR.21 phase III pivotal study · p.55 |
| Grade 1 or 2 rash (placebo) | 17 % | BR.21 phase III pivotal study · p.55 |
| Grade 1 or 2 diarrhoea | 48 % | BR.21 phase III pivotal study · p.55 |
| Grade 1 or 2 rash | 66 % | BR.21 phase III pivotal study · p.55 |
| grade 3 rash | 1 | Case study 1 · p.68 |
| grade 4 neutropenia | 1 | Case study 2 · p.68 |
| grade 3 skin rash | 1 | Case study 2 · p.69 |
| PFS HR 95% CI upper bound for erlotinib vs placebo in EGFR wild-type subgroup (BR.21) | 0.81 | BR.21 · p.13 |
| Opinion date | 09 November 2017 | · p.3 |
| PFS HR 95% CI lower bound for erlotinib vs placebo in full analysis set (BR.21) | 0.54 | BR.21 · p.13 |
| Inhibitory constant for del(746-750) in exon 19 | 3.3 nmol/L | · p.10 |
| Inhibitory constant for L858R mutation | 6.3 nmol/L | · p.10 |
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 →