Efficacy of trastuzumab beyond progression as second-line chemotherapy for HER2-positive advanced gastric cancer

Figures & data

Table 1 Characteristics of the 21 patients with HER2-positive AGC receiving (11) versus not receiving (10) TBP

Characteristic	n (%)		p-value
	ReceivingTBP (n=11)	Not receiving TBP (n=10)
Sex
Male	10 (91)	6 (60)	0.15
Age (years)
Mean±SD	62.6± 11.6	62.4±10.4	0.96
Diagnosis status
Metastasis	9 (82)	9 (90)	0.60
Recurrence	2 (18)	1 (10)
Histology
Intestinal	7 (63)	2 (20)	0.21
Diffuse	3 (27)	4 (40)
Mixed	1 (0)	3 (30)
Unknown	0 (0)	1 (10)
HER2 status (IHC)
IHC 3+	9 (82)	5 (50)	0.18
IHC 2+	2 (18)	5 (50)
HER2 status (DISH)
Mean±SD	7.0±4.4	4.5±2.2	0.12
Site of metastasis^a
PI and/or CYI	4	6	0.62
HI	6	2
LYM	1	1
PUL	1	0
OTH	2	2
First-line regimen
XP+trastuzumab	1 (9)	0 (0)	1.00
SP+trastuzumab	10 (91)	10 (100)

Note:

a Three patients receiving TBP and one patient not receiving TBP have double metastasis sites.

Abbreviations: HER2, human epidermal growth factor receptor 2; AGC, advanced gastric cancer; TBP, trastuzumab beyond progression; IHC, immunohistochemistry; DISH, dual-color in-situ hybridization; P1, peritoneal metastasis; CY1, peritoneal cytology positive for carcinoma cells; H1, hepatic metastasis; LYM, lymph nodes; PUL, lung; OTH, others; XP, capecitabine+cisplatin; SP, S-1+cisplatin.

Figure 1 Median OS (A) and PFS (B) of the second-line TBP therapy.

Notes: (A) OS after starting the second-line therapy of patients receiving TBP as the second-line therapy. (B) PFS after starting the second-line therapy of patients receiving TBP as the second-line therapy.
Abbreviations: OS, overall survival; PFS, progression-free survival; TBP, trastuzumab beyond progression.

Figure 2 Median OS (A and B) and PFS (C) after starting the first-line therapy.

Notes: (A) OS after starting the first-line therapy for all 21 patients. (B) OS after starting the first-line therapy stratified by the presence or absence of TBP as the second-line therapy. (C) PFS after starting the first-line therapy stratified by the presence or absence of TBP as the second-line therapy.
Abbreviations: OS, overall survival; PFS, progression-free survival; TBP, trastuzumab beyond progression.

Figure 3 The PFS after the first-line chemotherapy, the duration of TBP and the OS are depicted as bar charts, in addition to the clinical outcomes of the first-line chemotherapy.

Abbreviations: PFS, progression-free survival; TBP, trastuzumab beyond progression; OS, overall survival; PR, partial response; CR, complete response; Pt, patient; AE, adverse events; SD, stable disease.

Table 2 Hematologic adverse events of patients receiving TBP

Hematologic adverse events	n (%)
	All	Grade 3/4
Neutropenia	6 (55)	2 (18)
Anemia	11 (100)	0 (0)
Thrombocytopenia	1 (9)	0 (0)
Febrile neutropenia	0 (0)	0 (0)
Elevation of AST	6 (55)	0 (0)
Elevation of ALT	4 (36)	0 (0)
Elevation of T-Bil	0 (0)	0 (0)
Hypoalbuminemia	11 (100)	1 (9)
Hyponatremia	0 (0)	0 (0)
Hyperkalemia	3 (27)	0 (0)
Hypokalemia	0 (0)	0 (0)
Creatinine increased	1 (9)	0 (0)

Abbreviations: TBP, trastuzumab beyond progression; T-Bil, Total bilirubin; AST, aspartate transaminase; ALT, alanine transaminase.

Table 3 Outcomes of clinical trials for patients with HER2-positive AGC

Study	Setting	HER2 status	Treatment	n	mAge (years)	mOS (months)	HR (95% CI)	mPFS (months)	HR (95% CI)
ToGA^Citation1	Phase III trial	IHC3+ or	XP/FP	290	58.5	11.1	0.74 (0.60–0.91)	5.5	0.71 (0.59–0.85)
		FISH+	XP/FP+Tmab	294	59.4	13.8		6.7
		IHC3+ or	XP/FP	218	–	11.8	0.65 (0.51–0.83)	–	–
		2+/FISH+	XP/FP+Tmab	228	–	16.0		–
HERBIS-I^Citation2	Phase II trial	IHC3+ or	SP+Tmab	56	66	16.0	–	7.8	–
		2+/FISH+
Our study	Retrospective	IHC3+ or	XP/FP+Tmab	21	65	16.8	–	–	–
		2+/DISH+

Abbreviations: HER2, human epidermal growth factor receptor 2; AGC, advanced gastric cancer; mAge, median age; mOS, median overall survival; HR, hazard ratio; mPFS, median progression-free survival; IHC, immunohistochemistry; FISH, fluorescence in situ hybridization; XP, capecitabine+cisplatin; FP, 5-FU+cisplatin; Tmab, trastuzumab; SP, S-1+cisplatin; DISH, dual-color in-situ hybridization.

Bang YJ, Van Cutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376(9742):687–697.

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Kurokawa Y, Sugimoto N, Miwa H, et al. Phase II study of trastuzumab in combination with S-1 plus cisplatin in HER2-positive gastric cancer (HERBIS-1). Br J Cancer. 2014;110(5):1163–1168.

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