quality of life results from a phase iii trial of trastuzumab plus chemotherapy in first-line...
TRANSCRIPT
Quality of life results from aPhase III trial of trastuzumab
plus chemotherapy in first-lineHER2-positive advanced gastric
and GE junction cancer
Taroh Satoh*
*Kinki University School of Medicine, Osaka, Japan
J León Chong, RI López Sanchez, D Ferry, Y-J Bang, E Van Cutsem, N Al-Sakaff, J Hill, S Donelson Trease, G
Aprile
Disclosures
• Travel support from:
• Chugai Pharmaceutical
• Consultancy fees from:
• Chugai Pharmaceutical
• Merck-Serono
• Sanofi-Aventis
• Bristol-Myers
• Yakult Pharmaceutical
• Taiho Pharmaceutical
• Daiichi-Sankyo
Gastric cancer overview
• Gastric cancer is the fourth most commonly diagnosed cancer and the second most common cause of cancer-related deaths worldwide1,2
• Despite an overall decrease in gastric cancer there is a growing incidence of gastro-esophageal (GE) junction tumors in developed countries3
• Advanced/metastatic gastric cancer has a poor prognosis
• Median 5-year survival rate of around 20%2
• There is an unmet need for more efficacious and less toxic treatment options in advanced GC
1. Kamangar F, et al. J Clin Oncol 2006; 24:2137–2150.2. Garcia M, et al. Global Cancer Facts and Figures 2007. Atlanta GA: American Cancer Society 2007.
3. Kusano C, et al. J Gastroenterol Hepatol 2008; 23:1662–1665.
ToGA trial design
HER2-positiveadvanced GC
(n=584)
Capecitabineor 5-FU + cisplatin
(XP/FP)(n=290)
R
5-FU, 5-fluorouracil; GC, gastric cancer; R, randomised.Van Cutsem E, et al. J Clin Oncol 2009; 27(18s):Abstract LBA4509.
Capecitabineor 5-FU + cisplatin
(XP/FP)+ trastuzumab
(n=294)
● Primary objective: overall survival (OS)
● Secondary endpoints included: PFS, TTP,ORR, Clinical Benefit Rate, Duration of Response, safety, quality of life, pain intensity, analgesic consumption
3,807 patients screened;810 HER2-positive
● Phase III, randomized, global study to evaluate the efficacy and safety of trastuzumab in patients with advanced, HER2-positive adenocarcinoma of the stomach or GE junction
OS in the full analysis set
Van Cutsem E, et al. J Clin Oncol 2009; 27(18s):Abstract LBA4509.
Median OS HR 95% CI p-value
Trastuzumab+ XP/FP
167 13.8 mo 0.74 0.60, 0.91 0.0046
XP/FP 182 11.1 mo
Time (months)
11.1 13.8
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36
Events
0.00.10.20.30.40.50.60.70.80.91.0
Pro
bab
ility
294290
277266
246223
209185
173143
147117
11390
9064
7147
5632
4324
3016
2114
137
126
65
40
10
00
No. at risk
OS in IHC 2+/FISH+ or IHC 3+ patients (exploratory analysis)
Van Cutsem E, et al. J Clin Oncol 2009; 27(18s):Abstract LBA4509.
Median OS HR 95% CI
Trastuzumab+ XP/FP
120 16.0 mo 0.65 0.51, 0.83
XP/FP 136 11.8 mo
0.00.10.20.30.40.50.60.70.80.91.0
Time (months)
Events
11.8 16.0
2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 360
Pro
bab
ility
113
218 198
53
124
2011
228 218
196 170
170 141
142 112
12296
10075
8453
6539
5128
3920
2813
No. at risk
00
10
40
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34
294290
258238
201182
14199
9562
6033
4117
287
215
133
93
82
62
61
61
40
20
00
5.5 6.7
No. at risk
0.00.10.20.30.40.50.60.70.80.91.0
Time (months)
Trastuzumab+ XP/FP
XP/FP
Events
226
235
HR
0.71
95% CI
0.59, 0.85
p value
0.0002
MedianPFS
6.7
5.5
Pro
bab
ility
PFS in the full analysis set
Van Cutsem E, et al. J Clin Oncol 2009; 27(18s):Abstract LBA4509.
Methods: QoL assessments
1. Vickery CW, et al. Eur J Cancer 2001; 37:966–971. 2. Blazeby JM, et al. Eur J Cancer 2004; 40:2260–2268.
• Evaluated in the full analysis set (FAS) population at Day 1 and every 3 weeks (prior to drug administration), until disease progression
• EORTC QLQ-C30 questionnaire (v 3.0):1,2
• Global health status, functional scales, symptom scales
• EORTC QLQ-ST022 questionnaire (disease-specific module for gastric cancer):1,2
• Symptom scales included items for disease, treatment-related symptoms, side effects, dysphagia, nutritional aspects, emotional problems
• The scoring range for both QLQ-C30 and QLQ-ST022 was from 0–100
• Pain intensity assessed by Visual Analog Scale (VAS)
• Analgesic consumption for gastric pain
Compliance
• At baseline, >95% of patients in both treatment arms completed the EORTC QLQ-C30 and EORTC QLQ-ST022 questionnaires
• Compliance remained high for patients continuing in the study
Compliance to QLQ-C30, n/N (%)
Visit
Trastuzumab +
Chemotherapy (n=294)
Chemotherapy alone
(n=290)
Baseline 287/294 (97.6%) 276/290 (95.2%)
Week 16 165/168 (98.2) 121/126 (96.0)
Week 25 124/129 (96.1) 64/69 (92.8)
Week 34 87/89 (97.8) 37/39 (94.9)
*Higher global health score indicates better QoL; B/L, baseline
EORTC QLQ-C30: global health status scores improved over time
B/L
50
4 7 10 13 16 19 22 25 28 31 34 37 40 43 46 49 52 55 58 61 64
55
60
75
80
85
90
Sco
re (
mea
n ±
SE
M)*
Time (weeks)
70
65
Duration ofchemotherapy
Trastuzumab + Chemotherapy (n=287)
Chemotherapy alone (n=274)
N
235 180 176 152 121 114 78 64 47 45 36 29 23 12 13 9 7 5 5 4 3274Chemo287 249 220 202 182 165 143 143 124 111 95 87 64 55 43 42 36 29 24 21 17 20T + chemo
EORTC QLQ-C30: physical functioning scores improved over time
Trastuzumab + Chemotherapy (n=287)
Chemotherapy alone (n=276)
B/L
70
4 7 10 13 16 19 22 25 28 31 34 37 40 43 46 49 52 55 58 61 64
75
80
85
80
95
100
Sco
re (
mea
n ±
SE
M)*
Time (weeks)
*Higher functioning score indicates better QoL; B/L, baseline
Duration ofchemotherapy
N
235 181 174 151 121 114 79 64 47 45 37 29 24 12 14 10 8 6 6 4 3276Chemo287 250 220 201 183 165 143 143 124 110 95 87 64 55 43 42 36 30 24 21 17 20T + chemo
*Lower symptom score indicates better QoL; B/L, baseline
EORTC QLQ-C30: symptom scores for nausea/vomiting improved over time
5
10
15
20
25
Sco
re (
mea
n ±
SE
M)*
0
B/L 4 7 10 13 16 19 22 25 28 31 34 37 40 43 46 49 52 55 58 61 64
Time (weeks)
Duration ofchemotherapy
Trastuzumab + Chemotherapy (n=287)
Chemotherapy alone (n=276)
N
235 181 176 152 121 114 79 64 47 45 37 29 24 12 14 10 8 6 6 4 3276Chemo287 250 220 201 183 165 143 143 124 110 95 87 64 55 43 42 36 30 24 21 17 20T + chemo
EORTC QLQ-ST022: mean dysphagia score improved over time
5
10
15
20
0
Sco
re (
mea
n ±
SE
M)*
B/L 4 7 10 13 16 19 22 25 28 31 34 37 40 43 46 49 52 55 58 61 64
Time (weeks)
Trastuzumab + Chemotherapy (n=287)
Chemotherapy alone (n=276)
Duration ofchemotherapy
*Lower symptom score indicates better QoL; B/L, baseline
N
287 250 220 203 183 165 143 143 124 111 95 87 64 55 43 42 36 30 24 21 17 20T + chemo234 181 176 152 120 114 79 64 47 45 37 29 24 12 14 10 8 6 6 4 3276Chemo
No difference in VAS pain intensity scores over time
Trastuzumab + Chemotherapy (n=284)
Chemotherapy alone (n=275)
5
10
20
25
0
Sco
re (
mea
n ±
SE
M)*
B/L 4 7 10 13 16 19 22 25 28 31 34 37 40 43 46 49 52 55 58 61 64
Time (weeks)
*Lower pain intensity score indicates better QoL; B/L, baseline
15
Duration ofchemotherapy
N
234 181 174 152 121 114 79 64 47 45 37 29 24 12 14 10 8 6 6 4 3275Chemo284 249 219 202 181 165 142 141 124 111 95 86 64 54 43 41 36 30 24 20 17 20T + chemo
Analgesic medication for gastric pain during the study
Patients, n (%)
Trastuzumab + Chemotherapy
n=294
Chemotherapy alone
n=290
Any analgesic medication 86 (29) 84 (29)
Discontinued at least one medication
5 (2) 17 (6)
Decreased dose of at least one medication
1 (<1) 1 (<1)
No change in any medication 21 (7) 16 (6)
Increased dose or added at least one medication
59 (20) 50 (17)
Conclusions
• Trastuzumab + chemotherapy improves OS and PFS versus chemotherapy alone, without compromising QoL
• Disease-specific and symptom-specific scores improved over time in both treatment arms
• Pain intensity scores and use of analgesic medicine were similar between treatment arms
• Associated with prolonged PFS more patients in the trastuzumab + chemotherapy arm could benefit from the improved QoL compared to chemotherapy alone
Acknowledgements
The authors would like to thank:
• The patients
• The investigators, co-investigators and study teams at the 142 centres in 24 countries (in Asia, Australia, Europe, Latin-America, and South Africa)
• The study team at Roche
• Targos Molecular Pathology GmbH