Table 2.
Summary of efficacy endpoints of the NALA trial (neratinib), HER2Climb trial (tucatinib) and PHENIX trial (pyrotinib)
| Endpoint (NALA trial) | Neratinib + capecitabine (N + C) | Lapatinib + capecitabine (L + C) | P |
| Mean PFS | 8.8 months | 6.6 months | 0.0059 |
| Median PFS | 5.6 months | 5.5 months | |
| 6-month PFS rate | 47.2% | 37.8% | |
| 12-month PFS rate | 28.8% | 14.8% | |
| 18-month PFS rate | 16.3% | 7.4% | |
| Mean OS | 24.0 months | 22.2 months | 0.2086 |
| Median OS | 21.0 months | 18.7 months | |
| Cumulative incidence of intervention for CNS disease | 22.8% | 29.2% | 0.0430 |
| ORR | 32.8% | 26.7% | 0.1201 |
| DOR | 8.5 months | 5.6 months | 0.0004 |
| Endpoint (HER2CLIMB trial) | Tucatinib combination | Placebo combination | P |
| Median PFS | 7.6 months | 4.9 months | < 0.00001 |
| 1-year PFS rate | 29% | 14% | |
| Median OS | 24.7 months | 19.2 months | 0.004 |
| 2-year OS rate | 51% | 40% | |
| Median CNS-PFS | 9.9 months | 4.6 months | |
| Median CNS-OS | 21.6 months | 12.5 months | |
| Confirmed ORR-IC | 47.3% | 20.0% | |
| median DOR-IC | 8.6% | 3.0% | |
| Endpoint (PHENIX trial) | Pyrotinib + capecitabine | Placebo + capecitabine | P |
| Median PFS | 11.1 months | 4.1 months | < 0.001 |
| Median CNS-PFS | 6.9 months | 4.2 months | 0.011 |
| ORR | 68.6% | 16.0% | < 0.001 |
| DOR | 12.2 months | 4.2 months | < 0.001 |
| DCR | 91.9% | 64.9% | < 0.001 |
| CBR | 76.8% | 22.3% | < 0.001 |
PFS, progression-free survival; OS, overall survival; CNS, central nervous system; ORR, objective response rate; DOR, duration of response; DOR-IC, duration of intracranial response; ORR-IC, intracranial objective response rate, Tucatinib combination: tucatinib, trastuzumab, and capecitabine; Placebo combination: placebo, trastuzumab, and capecitabine; CBR, clinical benefit rate