Table 3. Summary of Subset Analysis for Combination of Two Small Molecule Inhibitors, as well as Small Molecule Inhibitor and Antibody Combinationsa.
| Combination of Two Small Molecule Inhibitors (N = 68 Studies) | ||
| Second drug at 100% dose percentage of FDA-approved dose/RP2D/MTD | Lowest additive dose percentage of the combination | |
| First drug at 100% dose percentage of FDA-approved dose/RP2D/MTD | 44% of trials(25/57)(Note: 25 of the 68 total trials (37%) administered each drug at 100% dose) | 125%b |
| First drug at 51-99% dose percentage of the FDA-approved dose/RP2D/MTD | Not applicable(9 total trials) | 104%c |
| First drug at ≤ 50% dose percentage of the FDA-approved dose/RP2D/MTD | Not applicable(2 total trials) | 90%d |
| Combination of Small Molecule Inhibitor and Antibody Combinations (N = 62 Studies) | ||
| First drug at 100% dose percentage of FDA-approved dose/RP2D/MTD | 73% of trials(40/55)(Note: 40 of the 62 total trials (65%) administered each drug at 100% dose) | 150%e |
| First drug at 51-99% dose percentage of the FDA-approved dose/RP2D/MTD | Not applicable(4 total trials) | 117%f 143% (for non-overlapping targets)g |
| First drug at ≤ 50% dose percentage of the FDA-approved dose/RP2D/MTD | Not applicable(3 total trials) | 60% (overlapping targets in each case)h |
a
All combinations of two antibodies had each drug given at 100% of the FDA-approved/RP2D/MTD dose
b
In these cases, the combinations had non-overlapping targets (sorafenib at 100% with everolimus at 25%, and imatinib at 100% with everolimus at 25%) [12–14].
c
Sunitinib was at 75% and everolimus at 29% [20]
d
Sorafenib was at 50% and temsirolimus at 40% [23].
e
Bevacizumab and erlotinib were each given at 50% and 100%, respectively [15–17] while panobinostat and bevacizumab were given at 50% and 100%, respectively [18].
f
Vandetanib was at 67% and bevacizumab was at 50% [21].
g
Rapamycin was at 93% and bevacizumab was at 50% [19].