quality of life results from a phase iii trial of trastuzumab plus chemotherapy in first-line...

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)


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


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



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


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)




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)




*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



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


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

quality of life results from a phase iii trial of trastuzumab plus chemotherapy in first-line...

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