HER2 inhibition in gastro-oesophageal cancer: A review drawing on lessons learned from breast cancer

Table 1 Summary of selected randomized phase III HER2 trials in HER2-amplified gastro-oesophageal cancer and breast cancer

Study title	Setting	n	Treatment arms	Primary endpoint	OS	PFS	HR and P value
Trastuzumab 1st line metastatic
ToGA[5]	1st line metastatic GOC	594	Trastuzumab + chemotherapy vs chemotherapy alone	OS	Trastuzumab + chemotherapy: 13.8 mo (95%CI: 12-16) Chemotherapy alone: OS 11.1 mo (10-13)	Trastuzumab + chemotherapy: 6.7 mo (95%CI: 6-8) Chemotherapy alone: 5.5 mo (5-6)	HR = 0.74; 95%CI: 0.60-0.91; P = 0.0046)
Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2[19]	1st line metastatic breast cancer	469	Trastuzumab + chemotherapy vs chemotherapy alone	PFS	Trastuzumab + chemotherapy: 25.1 mo Chemotherapy alone: 20.3 mo	Trastuzumab + chemotherapy: 7.4 mo Chemotherapy alone: 4.6 mo	P = 0.046
Lapatinib 1st line metastatic
LOGiC[7]	1st line metastatic GOC	545	Lapatinib + CAPOX vs Placebo + CAPOX	OS	Lapatinib + CAPOX: 12.2 mo (95%CI: 10.6-14.2) Placebo + CAPOX: 10.5 mo (9.0-11.3)	Lapatinib + CAPOX: 6 mo (95%CI: 5.6-7.0) Placebo + CAPOX: 5.4 mo (4.4-5.7)	HR = 0.91; 95%CI: 0.73-1.12 P value not significant (exact value not given)
Randomized trial of lapatinib vs placebo added to paclitaxel in the treatment of human epidermal growth factor receptor 2-overexpressing metastatic breast cancer[29]	1st line metastatic breast cancer	444	Lapatinib + paclitaxel vs Placebo + paclitaxel	OS	Lapatinib + paclitaxel: 27.8 mo (95%CI: 23.2-32.2 mo) Placebo + paclitaxel: 20.5 mo (17.9-24.3 mo)	Lapatinib + paclitaxel: 9.7 mo (95%CI: 9.2-11.1 mo) Placebo + paclitaxel: 6.5 mo (5.5-7.3 mo)	HR = 0.74; 95%CI: 0.58-0.94; P = 0.0124
Lapatinib 2nd line metastatic
Tytan[8]	2nd line metastatic GOC	261	Lapatinib + Paclitaxel vs Paclitaxel alone	OS	Lapatinib + Paclitaxel: 11.0 mo Paclitaxel alone: 8.9 mo	Lapatinib + Paclitaxel: 5.5 mo Paclitaxel alone: 4.4 mo	HR = 0.84; 95%CI: 0.64-1.11 P = 0.1044
Lapatinib plus capecitabine for HER2-Positive advanced breast Cancer[30]	2nd line metastatic breast cancer	324 included in preliminary analysis	Lapatinib + capecitabine vs capecitabine alone	PFS	Not reported	Lapatinib + capecitabin: 8.4 mo Capecitabine alone: 4.4 mo	HR = 0.49; 95%CI: 0.34 to 0.71; P < 0.001
T-DM1 2nd line metastatic
GATSBY[35]	2nd line metastatic GOC	345	T-DM1 vs taxane	OS	T-DM1: 7.9 mo Taxane: 8.6 mo	T-DM1: 2.7 mo Taxane: 2.9 mo	HR = 1.15, 95%CI: 0.87–1.51; P = 0·86
EMILIA[33]	2nd line metastatic breast cancer	991	T-DM1 vs lapatinib + capecitabine	PFS	T-DM1: 30.9 mo Lapatinib + capecitabine: 25.1 mo	T-DM1: 9.6 mo Lapatinib + capecitabine: 6.4 mo	HR = 0.65; 95%CI: 0.55 to 0.77; P < 0.001

HER2: Human epidermal growth factor receptor 2.