Table 3.
Comparison of anti-tumor response of lenvatinib after PD-1/PD-L1 with that of lenvatinib monotherapy, and anti-VEGF and anti-PD-1 blockade combinations.
| Study Name/ID | REFLECT [8] | Presented Study | NCT03006926 | NCT03434379 |
|---|---|---|---|---|
| Treatment | Monotherapy | Sequential | Combination | |
| Agents | Lenvatinib | Lenvatinib after PD-1/PD-L1 |
Lenvatinib + Pembrolizumab | Atezolizumab + Bevacizumab |
| Condition | ||||
| Design | Phase Ⅲ | Retrospective | Phase Ⅰ b | Phase Ⅲ |
| Number of patents | 478 | 36 | 100 | 336 |
| Setting | 1st line | 2–4th line | 1st line | 1st line |
| Outcome | ||||
| ORR (mRECIST) | 24.1% | 55.6% | 46.0% | 33.2% |
| DCR (mRECIST) | 73.8% | 86.1% | 86.0% | 72.3% |
| median PFS | 7.4 months | 10 months | 9.3 months | 6.8 months |
| median OS | 13.6 months | 15.8 months | 22 months | (12 months, OS 67.2%) |
| (29.8 months since ICIs started) | ||||
| Adverse events | HT 42% | HT 44% | HT 36% | HT 30% |
| diarrhea 39% | diarrhea 42% | diarrhea 35% | diarrhea 19% | |
| appetite loss 34% | appetite loss 42% | fatigue 30% | fatigue 20% | |
| weight loss 31% | fatigue 36% | AST increase 20% | AST increase 20% | |
| AST increase 14% | AST increase 58% | |||
| any grade 99% | ||||
| any grade 99% | any grade 100% | grade 3, 85% | Any grade 98% | |
| grade 3,4; 75% | grade 3,4; 56% | grade 4, 23% | Grade 3,4; 57% | |
ORR, objective response rate; DCR, disease control rate; PFS, progression-free survival; OS, overall survival; mRECIST, modified Response Evaluation Criteria in Solid Tumors; ICI, immune checkpoint inhibitor; PD−1, programmed cell death protein 1; PD-L1, PD-ligand 1; HT, hypertension; AST, aspartate aminotransferase. NCT03006926 [32] and NCT03434379 [27].