Upload
christina-douglas
View
216
Download
1
Embed Size (px)
Citation preview
www.OncologyEducation.ca
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
www.OncologyEducation.ca
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)
www.OncologyEducation.ca
Key Demographics
• 55% Asian• 97% metastatic disease• 88% received capecitabine
www.OncologyEducation.ca
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
www.OncologyEducation.ca
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
www.OncologyEducation.ca
Grade 3/4 Toxicity (%)
F+Cn=290
F+C + trastuzumab
n=294
NauseaVomitingFatigueDiarrheaConstipationAstheniaStomatitisWeight decreaseAbdominal pain
782423221
7649
<14
<121
www.OncologyEducation.ca
Grade 3/4 Toxicity (%)
F+Cn=290
F+C + trastuzumab
n=294
Asymp LVEF Drops<50%
<50% + > 10%
Cardiac Failure
11
<1
65
<1
www.OncologyEducation.ca
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
www.OncologyEducation.ca
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
www.OncologyEducation.ca
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?