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