Metastatic gastric cancer – focus on targeted therapies

Figures & data

Table 1 Targeted therapies for advanced gastric cancer

Targets	Drugs	Trade mark/company
Antiangiogenic therapy
Anti-VEGF	Bevacizumab	Avastin^®/Roche
Humanized mAB	Ramucirumab	IMC-1121B/ImClone Systems
VEGFR TKI	Cediranib	Recentin^®/AstraZeneca
	Sorafenib	Nexavar^®/Bayer
	Sunitinib	Sutent^®/Pfizer
Anti EGFR therapy
EGFR antibody
Chimeric (mouse/ human) mAB	Cetuximab	Erbitux^®/Bristol-Myers Squibb
Humanized mAB	Panitumumab	Vectibix^®/Amgen
Humanized mAB	Matuzumab	EMD 72000/Merk
Humanized mAB	Nimotuzumab	TheraCIM^®/CIMYM Biosciences
EGFR TKI	Gefitinib	Iressa^®/AstraZeneca
	Erlotinib	Tarceva^®/Genentech and OSI Pharmaceuticals
Her-2 humanized mAB	Traztuzumab	Herceptin^®/Roche
Her-2 TKI	Lapatinib	Tykerb^®/Tyverb^®/GlaxoSmithKline plc

Abbreviations: VEGF, vascular endothelial growth factor; TKI, tyrosine kinase inhibitor; EGFR, epidermal growth factor receptor; mAbs, monoclonal antibodies.

Figure 1 Relevant anti VEGF pathways therapies in advanced gastric cancer.

Abbreviations: VEGF, vascular endothelial growth factor; VEGFR, vascular endothelial growth factor receptor; PGF, placenta growth factor.

Table 2 Phase II and III studies of bevacizumab combined with chemotherapy for advanced GC in a first-line setting

Author/type of study	N	Bevacizumab + chemotherapy	% RR	TTP months	OS months	Grade 3–4 toxicity (%)
Shah et al^Citation10	47	Cisplatin/irinotecan	65	8.3	12.3	HT: 28, TEE: 25
Phase II						GIP: 6, MI: 2
Shah et al^Citation11	44	Docetaxel/cisplatin/5-FU	67	12	16.2	NTP: 50, Fatigue: 5
Phase II						TEE: 39, ╩ Other: <10
Enzinger et al^Citation12, ☖	26	Docetaxel/cisplatin/irinotecan	24	NA	NA	NTP: 22, Diarrhea: 28
Phase II						Nausea: 6, TEE: 9
El-Reyes et al^Citation13	38	Oxaliplatin/docetaxel	59	66	11.1	NTP: 34
Phase II						GIP: 8
Cohenuram and Lacy^Citation14	16	FOLFOX	63	7	8.9	TEE: 0, GIP: 0
Retrospective
Ohtsu et al^Citation15,*	387	Bevacizumab + cisplatin/capecitabine	46⊖	6.7§	12.1Π	TEE: 7, GIP: 2
Phase III	387	Placebo + cisplatin/capecitabine	37.4	5.3	10.1	TEE: 7, GIP: 2

Notes:

* AVAGAST;

⊖ P = 0.0315;

§ PFS P = 0.0037;

Π P = 0.1002;

☖ tumor partial responses were 63% and stable disease 30%;

╩ other includes gastrointestinal toxicity, neuropathy, and febrile neutropenia.

Abbreviations: RR, response rate; TTP, time to progression; OS, overall survival; PFS, progression free survival; NA, data is not available; HT, hypertension; TEE, thromboembolic events; MI, myocardial infarction; GIP, gastrointestinal perforation.

Figure 2 Molecular targets and relevant drugs (anti-EGFR/Her-2) in advanced gastric cancer.

Abbreviations: AKT, protein kinase B; MAPK, mitogen-activated protein kinase; MEK, MAP kinase kinase; mTOR 1&2, mammalian target of rapamycin 1&2; PI3K, phosphatidylinositol 3 kinase; Raf, GTPase Raf; Ras, GTPase Ras; SOS, son of sevenless homolog.

Table 3 Anti EGFR therapy for advanced gastric cancer

Study/phase	Treatment	N	% RR	TTP months	OS months	Grade 3–4 toxicity (%)
CALGB 80403/ ECOG 1206^Citation36	ECF + cetuximab	67	57.8	5.9	11.5	Hem: 51, nonHem: 60
	IC + cetuximab	71	45.6	5	8.9	Hem: 56, nonHem: 70
	FOLFOX + cetuximab	72	53.6	6.7	12.4	Hem: 45, nonHem: 64
MATRIX^Citation41	ECX	36	58	7.1	12.2	NTP: 33, SD: 33
Phase II	ECX + matuzumab	35	31	4.8	9.4	NTP: 37, SD: 66
REAL III	EOX EOX + chemotherapy	NA	NA	NA	NA	NA
Phase II^Citation42	Irinotecan	40	NA	73 days*	293 days	NA
second-line	Irinotecan + nimotuzumab	42		85 days*	227 days
ToGA^Citation51	Capecitabine/5-FU + cisplatin + trastuzumab	298	NA	6.7*	13.5	Overall: 68, CE: 6
Phase II	Capecitabine/5-FU + cisplatin	296		5.5*	11.1	Overall: 68, CE: 6
TYTAN^Citation56,⊖	Paclitaxel + lapatinib	NA	NA	NA	NA	NA
Phase III	Paclitaxel
LOGiC^Citation57	Capecitabine + oxaliplatin + lapatinib Capecitabine + oxaliplatin + placebo	NA	NA	NA	NA	NA

Notes:

* Progression free survival;

⊖ second line of treatment.

Abbreviations: Hem, hematological toxicity; NTP, neutropenia; OS, overall survival; SD, skin disorders; CE, cardiac events; RR, reported response rates; TTP, time to progression.

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