1. 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

2. R N= 810 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)
+ Cisplatin
80 mg/m2 q3w x 6
N= 810
(22% pts of
3807 screened) R
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+)
Locally
Advanced/
Metastatic
Gastric CA

3. Key Demographics 55% Asian 97% metastatic disease
88% received capecitabine

4. Results 35% 47% 0.0017 5.5 mos 6.7 mos 0.0002 11.1 mos 13.8 mos 0.0046
Chemo
Chemo+
Trastuzumab
p-value
Response Rate (%)
35%
47%
0.0017
PFS
(median, mos)
5.5 mos
6.7 mos
0.0002 OS
11.1 mos
13.8 mos
0.0046

5. Grade 3/4 Toxicity AE, % F+C n=290 F+C + trastuzumab n=294 Neutropenia
Febrile neutropenia
Anemia
Thrombocytopenia 30 3 10 27 5 12

6. Grade 3/4 Toxicity (%) F+C n=290 F+C + trastuzumab n=294 Nausea
Vomiting
Fatigue
Diarrhea
Constipation
Asthenia
Stomatitis
Weight decrease
Abdominal pain 7 8 2 4 3 1 6 9
<1

7. Grade 3/4 Toxicity (%) F+C n=290 F+C + trastuzumab n=294
Asymp LVEF Drops
<50%
<50% + > 10%
Cardiac Failure 1
<1 6 5

8. 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 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

9. 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 )
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

10. 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?