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Efficacy results from the ToGA trial: a phase III study of trastuzumab added to standard chemotherapy in first-line human

epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer

Authors: Van Cutsem et al

Reviewed by Scott Berry

Date posted: June 2009


R

5-FU (800 mg/m2/day continuous iv infusion d1-5 q3w x 6) Or Capecitabine(1000 mg/m2 bid d1-14 q3w x 6)

+ Cisplatin80 mg/m2 q3w x 6

5-FU or capecitabine + cisplatin(as above)

+ Trastuzumab(8 mg/kg loading dose followed by 6 mg/kg q3w until PD)

Her2+(IHC 3+ or FISH+)

LocallyAdvanced/Metastatic

Gastric CA

N= 810(22% pts of 3807 screened)


Key Demographics

• 55% Asian• 97% metastatic disease• 88% received capecitabine


ChemoChemo+

Trastuzumabp-value

Response Rate (%) 35% 47% 0.0017

PFS

(median, mos) 5.5 mos 6.7 mos 0.0002

OS

(median, mos)11.1 mos 13.8 mos 0.0046

Results


Grade 3/4 Toxicity

AE, %F+C

n=290

F+C + trastuzumab

n=294

Neutropenia

Febrile neutropenia

Anemia

Thrombocytopenia

30

3

10

3

27

5

12

5


Grade 3/4 Toxicity (%)

F+Cn=290

F+C + trastuzumab

n=294

NauseaVomitingFatigueDiarrheaConstipationAstheniaStomatitisWeight decreaseAbdominal pain

782423221

7649

<14

<121


Grade 3/4 Toxicity (%)

F+Cn=290

F+C + trastuzumab

n=294

Asymp LVEF Drops<50%

<50% + > 10%

Cardiac Failure

11

<1

65

<1


STUDY COMMENTARY

• Trastuzumab reduces the risk of death by 26% when combined with chemotherapy (HR 0.74)

– Prolongs the median survival by nearly 3 months (11.1 to 13.8 months; p=0.0046) in patients with HER2-positive advanced GC

– Improves PFS, ORR

• Addition of trastuzumab to chemotherapy was well tolerated: there was no difference in overall safety profile, including cardiac AEs, between treatment arms


STUDY COMMENTARY

• ? How would 5FU/Plat/Trastuzumab – compare to Canadian standard ECF

• Obviously no randomized trials yet

• Efficacy might be similar

– Wagner JCO 2008 : Meta-Analysis Anthracycline containing triplets vs 5FU/Platinum: HR 0.77 (95% CI – O.62-0.95)

– ToGA : 5FU/Plat/Trastuzumab vs 5FU/Platinum : HR 0.74

• Toxicity ?

– ToGA platinum dose higher (80 vs 60 mg/m2)

– But…. ECF has 50 mg/m2 epirubicin


BOTTOM LINE FOR CANADIAN MEDICAL ONCOLOGISTS

• 5FU/Platinum/Trastuzumab offers a new option for her2+ metastatic gastric cancer patients (~22% of all patents )

• Uncertain how this triplet would compare with Canadian standard ECF but will certainly be more costly so funding of trastuzumab will be an issue

• Planning for Her2 testing– Quality Issues: Different scoring system for IHC tesing due to

histologic differencees between breast and gastric cancer– Who pays?

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