Table 4 Clinical trials of TKIs in HER2-positive advanced G/GEJ adenocarcinoma

Lapatinib

TyTAN

2014 [90]

III

Completed

Second-line

HER2-positive GC

Lapatinib + Paclitaxel

Paclitaxel

132

129

mOS 11.0 m(P = 0.1044)

8.9 m

mPFS 5.5 m(P = 0.2441)

4.4 m

Grade 3 46%

45%

Grade 4 38%

9%

TRIO-013/LOGiC

2016 [91]

III

Completed

First-line

HER2-positive advanced GEA

Lapatinib + Capecitabine + Oxaliplatin

Placebo + Capecitabine + Oxaliplatin

249

238

mOS 12.2 m(P = 0.3492)

10.5 m

mPFS 6.0 m(P = 0.0381)

5.4 m

Grade 3 Diarrhea 12%

3%

Nausea 6%

2%

Elizabeth C Smyth 2019 [92]

II

Completed

Perioperation

HER2-positive GEA

Lapatinib + Epirubicin + Cisplatin + Capecitabine

Epirubicin + Cisplatin + Capecitabine

22

24

R0 resection 71%

69%

Grade 1–2 tumor regression 25%

9%

Neutropenia 53%

54%

Grade 3/4 Diarrhea 21%

0

Pyrotinib

Yuzhen Yin 2020 [95]

-

Completed

HER2-positive advanced solid tumors (except BC)

Pyrotinib/ + Capecitabine + Paclitaxel + Irinotecan + Pemetrexed + Osimertinib + Bevacizumab + Trastuzumab

25(GC 9)

mOS 9.6 m(GC 5.9个月)

mPFS 3.5 m(GC 2.9个月)

Grade 3 Diarrhea 20%

Sapitinib

Anne Thomas 2020 [97]

I

Completed

neoadjuvant therapy

HER2-positive resectable GEA

Sapitinib + Oxaliplatin + Capecitabine Oxaliplatin + Capecitabine

24

6-m PFS rate 85%

100%

12-m OS rate 80%

100%

Grade 3–4 50%

10%

Dacomitinib

Do-Youn Oh 2016 [98]

II

Completed

Second-line and beyond

HER2-positive GC

Dacomitinib

27

mOS 7.1 m

mPFS 2.1 m

Grade 3/4 Erythra 7%

Diarrhea 4%

Poziotinib

Tae Min Kim 2018 [99]

I

Completed

Second-line and beyond

HER2-positive advanced solid tumors

intermittent Poziotinib

continuous Poziotinib

55

20

DCR 63%

53%

mPFS 12w

9.0w

Grade ≥ 3 Diarrhea 15%

15%

Erythra 2%

0

Afatinib

Francisco Sanchez-Vega 2019 [101]

II

Completed

Second-line and beyond

HER2-oerexpressing advanced GEA

Afatinib

Afatinib + trastuzumab

20

12

mPFS 2 m

mOS 7 m

Grade 2 Diarrhea 0

42%