Table 4.
Treatments approved by FDA and/or EMA based on subgroup analysis
| Drug | Pivotal clinical trial | Setting | Disease | Primary endpoint(s) | Pivotal subgroup analysis | Subgroup | Agency |
|---|---|---|---|---|---|---|---|
| Atezolizumab | Impower 11027 |
First line | Advanced NSCLC | OS in preplanned subgroup | Preplanned subgroup | PD-L1 ≥50% of TC or IC ≥10% | FDA, EMA |
| Atezolizumab and nab-paclitaxel | Impassion 13017 |
First line | Advanced TNBC | OS and PFS preplanned subgroup and ITT | Preplanned subgroup | PD-L1 ≥1%. | FDA, EMA |
| Durvalumab | PACIFIC trial29 | Consolidation therapy after CT-RT | Locally advanced NSCLC | OS and PFS in ITT | Post hoc analysis | PD-L1 ≥1% | EMA |
| Nivolumab plus ipilimumab | CheckMate 22716 | First line | Advanced NSCLC | OS and PFS in preplanned subgroup | Preplanned subgroup | PD-L1 ≥1% | FDA |
| Olaparib plus bevacizumab | PAOLA-1 trial30 | First line maintenance | Advanced ovarian cancer | PFS in ITT | Prespecified subgroups | HRD-positive status (BRCA mutation, and/or genomic instability) | FDA, EMA |
| Pembrolizumab | KEYNOTE-04219 | First line | Advanced NSCLC | OS in preplanned subgroups and ITT | Preplanned subgroups | PD-L1 TPS ≥50% | FDA, EMA |
| Pembrolizumab single-agenta | KEYNOTE-04831 | First line | Advanced HNSCCs | PFS and OS in preplanned subgroups and ITT | Preplanned subgroups | PD-L1 CPS ≥1 % | FDA |
| Pembrolizumab with or without platinum and fluorouracil | KEYNOTE-04831 | First line | Advanced HNSCCs | PFS and OS in preplanned subgroups and ITT | Preplanned subgroups | PD-L1 CPS ≥1 % | EMA |
CPS, combined positive score; CT-RT, chemo-radiotherapy; IC, infiltrating immune cells; EMA, European Medicines Agency; FDA, Food and Drug Administration; HRD, homologous recombination deficiency; HNSCC, head and neck squamous cell carcinoma; ITT, intention to treat; NSCLC, non-small-cell lung cancer; OS, overall survival; PD-L1, programmed death-ligand 1; PFS, progression-free survival; TC, tumour cells; TNBC, triple-negative breast cancer; TPS, tumour proportion score.
a
Differently from EMA, the combination with platinum and fluorouracil (FU) was approved by FDA for all patients with metastatic head and neck tumours, regardless of PD-L1 level.