Skip to main content

Table 3 Sensitivity analysis

From: Lapatinib and lapatinib plus trastuzumab therapy versus trastuzumab therapy for HER2 positive breast cancer patients: an updated systematic review and meta-analysis

Trials

No. of patients

T+L/L

T

RR or HR (95% CI)

P-value

I2 (%)

OS (T+L vs. T)

 ALTTO

4190

2093

2097

0.83 [0.69, 1.01]

0.06

15%

 ALTTOa

4188

2091

2097

0.82 [0.68, 0.99]

0.04

12%

 CALGB 40601

238

118

120

0.86 [0.75, 0.99]

0.04

0%

 CHER-Lob

82

46

36

0.84 [0.73, 0.97]

0.02

15%

 NeoALTTO

301

152

149

0.85 [0.74, 0.99]

0.03

9%

 Pooled estimate

8999

4500

4499

0.84 [0.73, 0.97]

0.02

0%

OS (L vs. T)

 ALTTO

4197

2100

2097

1.18 [0.97, 1.45]

0.19

35%

 CALGB 40601

187

67

120

1.26 [1.08, 1.47]

0.003

43%

 CEREBEL

540

271

269

1.24 [1.05, 1.47]

0.01

42%

 GeparQuinto

615

308

307

1.32 [1.13, 1.54]

0.0006

0%

 NCIC CTG MA.31

537

270

267

1.22 [1.03, 1.44]

0.02

35%

 NeoALTTO

303

154

149

1.30 [1.11, 1.52]

0.001

16%

 Pooled estimate

6379

3170

3209

1.26 [1.08, 1.46]

0.003

29%

PFS (L vs. T)

 CEREBEL

540

271

269

1.47 [1.03, 2.09]

0.03

/

 NCIC CTG MA.31

537

270

267

1.30 [1.04, 1.64]

0.02

/

 Pooled estimate

1077

541

536

1.35 [1.11, 1.64]

0.002

0%

DFS/EFS (T+L vs. T)

 ALTTO

4190

2093

2097

0.91 [0.79, 1.04]

0.15

35%

 ALTTOa

4188

2091

2097

0.84 [0.73, 0.97]

0.01

10%

 CHER-Lob

82

46

36

0.89 [0.81, 0.99]

0.03

0%

 NeoALTTO

301

152

149

0.89 [0.80, 0.99]

0.03

36%

 Pooled estimate

8761

4382

4379

0.89 [0.80, 0.98]

0.02

9%

DFS/EFS (L vs. T) (REM)

 ALTTO

4197

2100

2097

0.98 [0.75, 1.27]

0.88

0%

 CHER-Lob

75

39

36

1.20 [0.98, 1.46]

0.08

28%

 GeparQuinto

615

308

307

1.12 [0.81, 1.55]

0.49

48%

 NeoALTTO

303

154

149

1.15 [0.87, 1.53]

0.31

45%

 Pooled estimate

5190

2601

2589

1.13 [0.91, 1.42]

0.27

36%

pCR (T+L vs. T, ypT0/is ypN0)

 CALGB 40601

233

116

117

1.29 [1.13, 1.48]

0.0002

27%

 CHER-Lob

79

43

36

1.25 [1.11, 1.41]

0.0003

14%

 EORTC 10054

100

48

52

1.29 [1.14, 1.47]

< 0.0001

21%

 LPT109096

66

33

33

1.29 [1.14, 1.46]

< 0.0001

16%

 NeoALTTO

290

145

145

1.19 [1.05, 1.35]

0.008

0%

 NSABP B-41

347

171

176

1.30 [1.12, 1.51]

0.0007

28%

 TRIO-US B07

92

58

34

1.29 [1.14, 1.46]

< 0.0001

25%

 Pooled estimate

1207

614

593

1.27 [1.13, 1.43]

< 0.0001

14%

pCR (L vs. T, ypT0/is ypN0)

 CALGB 40601

179

62

117

0.74 [0.65, 0.84]

<0.00001

28%

 CHER-Lob

71

35

36

0.73 [0.64, 0.82]

<0.00001

28%

 EORTC 10054

74

22

52

0.73 [0.65, 0.83]

<0.00001

32%

 GEICAM/2006-14

99

51

48

0.75 [0.66, 0.85]

<0.00001

14%

 GeparQuinto

615

308

307

0.76 [0.66, 0.89]

0.0005

23%

 LPT109096

67

34

33

0.73 [0.65, 0.83]

<0.00001

32%

 NeoALTTO

295

150

145

0.73 [0.65, 0.83]

<0.00001

32%

 NSABP B-41

347

171

176

0.67 [0.58, 0.77]

<0.00001

0%

 TRIO-US B07

70

36

34

0.74 [0.66, 0.84]

<0.00001

24%

 Pooled estimate

1817

869

948

0.73 [0.65, 0.83]

<0.00001

22%

pCR (T+L vs. T, ypT0/is ypN0/+)

 CALGB 40601

238

118

120

1.33 [1.15, 1.54]

<0.0001

63%

 EORTC 10054

100

48

52

1.33 [1.17, 1.52]

<0.0001

61%

 NeoALTTO

301

152

149

1.20 [1.05, 1.38]

0.008

0%

 NSABP B-41

348

171

177

1.41 [1.19, 1.67]

<0.0001

49%

 Pooled estimate

987

489

498

1.31 [1.16, 1.49]

<0.0001

45%

pCR (L vs. T, ypT0/is ypN0/+)

 CALGB 40601

187

67

120

0.80 [0.71, 0.91]

0.0005

60%

 EORTC 10054

74

22

52

0.79 [0.70, 0.89]

<0.0001

63%

 GEICAM/2006-14

99

51

48

0.81 [0.72, 0.92]

0.0007

47%

 GeparQuinto

615

308

307

0.84 [0.72, 0.98]

0.02

53%

 NeoALTTO

303

154

149

0.78 [0.69, 0.89]

0.0001

64%

 NSABP B-41

348

171

177

0.72 [0.62, 0.83]

<0.00001

0%

 Pooled estimate

1626

773

853

0.79 [0.70, 0.89]

<0.0001

54%

RFS (T+L vs. T) (REM)

 ALTTO

4190

2093

2097

0.32 [0.14, 0.71]

0.005

/

 CALGB 40601

238

118

120

0.86 [0.74, 1.00]

0.05

/

 Pooled estimate

4428

2211

2217

0.57 [0.22, 1.48]

0.25

82%

ORR (T+L vs. T)

 EORTC 10054

99

47

52

1.04 [0.98, 1.12]

0.21

58%

 LPT109096

66

33

33

1.02 [0.96, 1.09]

0.50

71%

 NeoALTTO

301

152

149

0.96 [0.90, 1.03]

0.28

0%

 NSABP B-41

331

164

167

1.05 [0.95, 1.17]

0.34

65%

 Pooled estimate

797

396

401

1.02 [0.96, 1.09]

0.53

56%

ORR (L vs. T)

 CEREBEL

540

271

269

1.00 [0.95, 1.04]

0.88

0%

 EORTC 10054

73

21

52

0.98 [0.93, 1.03]

0.48

0%

 GEICAM/2006-14

99

51

48

0.98 [0.93, 1.03]

0.43

0%

 GeparQuinto

615

308

307

0.98 [0.91, 1.06]

0.66

0%

 LPT109096

67

34

33

0.97 [0.93, 1.03]

0.32

0%

 NeoALTTO

303

154

149

0.97 [0.91, 1.02]

0.20

0%

 NSABP B-41

330

163

167

0.97 [0.91, 1.03]

0.34

0%

 Pooled estimate

2027

1002

1025

0.98 [0.93, 1.03]

0.41

0%

DCR (L vs. T)

 CEREBEL

540

271

269

0.96 [0.93, 1.00]

0.03

24%

 EORTC 10054

73

21

52

0.96 [0.91, 1.02]

0.21

0%

 GeparQuinto

615

308

307

0.93 [0.79, 1.09]

0.36

0%

 Pooled estimate

1228

600

628

0.96 [0.90, 1.01]

0.13

0%

Rate of BCS (T+L vs. T)

 CHER-Lob

81

45

36

1.00 [0.86, 1.16]

0.99

0%

 EORTC 10054

102

50

52

0.99 [0.86, 1.14]

0.88

0%

 NeoALTTO

286

143

143

0.97 [0.83, 1.14]

0.73

0%

 NSABP B-41

348

171

177

1.08 [0.90, 1.30]

0.40

0%

 Pooled estimate

817

409

408

1.01 [0.88, 1.15]

0.94

0%

Rate of BCS (L vs. T)

 CHER-Lob

74

38

36

0.95 [0.86, 1.05]

0.31

28%

 EORTC 10054

74

22

52

0.93 [0.84, 1.03]

0.16

0%

 GEICAM/2006-14

99

51

48

0.94 [0.85, 1.04]

0.22

29%

 GeparQuinto

615

308

307

0.97 [0.85, 1.11]

0.64

27%

 NeoALTTO

286

143

143

0.91 [0.82, 1.01]

0.08

0%

 NSABP B-41

348

171

177

0.98 [0.88, 1.09]

0.70

4%

 Pooled estimate

1496

733

763

0.94 [0.86, 1.04]

0.24

14%

CHF (T+L vs. T)

 TRIO-US B07

92

58

34

0.95 [0.73, 1.23]

0.71

65%

 NSABP B-41

351

173

178

1.00 [0.77, 1.31]

0.98

62%

 NeoALTTO

301

152

149

0.94 [0.73, 1.22]

0.66

75%

 EORTC 10054

103

50

53

0.95 [0.73, 1.23]

0.71

65%

 CHER-Lob

82

46

36

0.95 [0.73, 1.23]

0.71

65%

 CALGB 40601

235

117

118

0.95 [0.73, 1.23]

0.71

65%

 ALTTOa

4152

2076

2076

1.17 [0.84, 1.65]

0.35

55%

 ALTTO

4137

2061

2076

0.65 [0.44, 0.97]

0.04

31%

 Pooled estimate

9453

4733

4720

0.95 [0.73, 1.23]

0.71

65%

CHF (L vs. T)

 WJOG6110B/ELTOP

86

43

43

0.88 [0.61, 1.26]

0.47

55%

 TRIO-US B07

70

36

34

0.89 [0.62, 1.28]

0.54

45%

 NSABP B-41

351

173

178

0.88 [0.60, 1.28]

0.50

58%

 NeoALTTO

303

154

149

0.89 [0.62, 1.28]

0.54

45%

 GeparQuinto

615

308

307

0.79 [0.55, 1.15]

0.22

2%

 EORTC 10054

75

22

53

0.86 [0.60, 1.24]

0.43

45%

 CHER-Lob

78

39

39

0.89 [0.62, 1.28]

0.54

45%

 CALGB 40601

182

64

118

0.89 [0.62, 1.28]

0.54

45%

 ALTTO

4133

2057

2076

2.03 [0.92, 4.48]

0.08

18%

 Pooled estimate

5893

2896

2997

0.89 [0.62, 1.28]

0.54

45%

Decline of LVEF (T+L vs. T)

 TRIO-US B07

92

58

34

0.82 [0.67, 1.01]

0.06

64%

 NSABP B-41

351

173

178

0.82 [0.67, 1.01]

0.08

52%

 NeoALTTO

301

152

149

0.82 [0.67, 1.01]

0.06

64%

 EORTC 10054

103

50

53

0.82 [0.67, 1.01]

0.06

52%

 CHER-Lob

82

46

36

0.83 [0.67, 1.01]

0.07

62%

 CALGB 40601

235

117

118

0.82 [0.67, 1.01]

0.06

52%

 ALTTOa

4152

2076

2076

1.05 [0.80, 1.37]

0.72

0%

 ALTTO

4137

2061

2076

0.59 [0.43, 0.80]

0.0009

0%

 Pooled estimate

9453

4733

4720

0.82 [0.67, 1.01]

0.06

52%

Decline of LVEF (L vs. T)

 WJOG6110B/ELTOP

86

43

43

0.67 [0.50, 0.90]

0.008

0%

 TRIO-US B07

70

36

34

0.66 [0.49, 0.89]

0.006

0%

 NSABP B-41

351

173

178

0.67 [0.50, 0.90]

0.008

0%

 NeoALTTO

303

154

149

0.67 [0.49, 0.90]

0.008

0%

 GeparQuinto

615

308

307

0.68 [0.51, 0.93]

0.01

0%

 EORTC 10054

75

22

53

0.65 [0.48, 0.88]

0.005

0%

 CHER-Lob

75

39

36

0.67 [0.50, 0.91]

0.010

0%

 CALGB 40601

182

64

118

0.67 [0.50, 0.90]

0.008

0%

 ALTTO

4133

2057

2076

0.82 [0.30, 2.24]

0.70

0%

 Pooled estimate

5890

2896

2994

0.67 [0.50, 0.90]

0.008

0%

Diarrhea (T+L vs. T)

 ALTTO

4137

2061

2076

6.06 [4.37, 8.41]

<0.00001

28%

 ALTTOa

4152

2076

2076

11.39 [8.30, 15.63]

<0.00001

0%

 CALGB 40601

235

117

118

8.19 [6.36, 10.55]

<0.00001

61%

 CHER-Lob

82

46

36

8.25 [6.42, 10.61]

<0.00001

61%

 EORTC 10054

103

50

53

8.31 [6.46, 10.67]

<0.00001

62%

 LPT109096

63

31

32

8.35 [6.50, 10.72]

<0.00001

62%

 NeoALTTO

297

149

148

8.25 [6.38, 10.67]

<0.00001

62%

 NSABP B-41

351

173

178

8.11 [6.27, 10.49]

<0.00001

60%

 TRIO-US B07

92

58

34

8.30 [6.46, 10.67]

<0.00001

62%

 Pooled estimate

9512

4761

4751

8.32 [6.49, 10.68]

<0.00001

57%

Diarrhea (L vs. T)

 ALTTO

4133

2057

2076

3.81 [2.78, 5.21]

<0.00001

76%

 CALGB 40601

182

64

118

5.48 [4.28, 7.02]

<0.00001

82%

 CEREBEL

536

269

267

7.62 [5.73, 10.11]

<0.00001

11%

 CHER-Lob

75

39

36

5.52 [4.32, 7.05]

<0.00001

82%

 EORTC 10054

75

22

53

5.63 [4.41, 7.19]

<0.00001

83%

 GeparQuinto

615

308

307

5.76 [4.45, 7.46]

<0.00001

83%

 LPT109096

66

34

32

5.63 [4.41, 7.19]

<0.00001

83%

 NeoALTTO

299

151

148

5.40 [4.20, 6.95]

<0.00001

82%

 NSABP B-41

351

173

178

5.43 [4.22, 6.98]

<0.00001

82%

 TRIO-US B07

70

36

34

5.64 [4.41, 7.20]

<0.00001

83%

 WJOG6110B/ELTOP

86

43

43

5.85 [4.55, 7.51]

<0.00001

81%

 Pooled estimate

6488

3196

3292

5.62 [4.41, 7.17]

<0.00001

81%

Neutropenia (T+L vs. T)

 EORTC 10054

103

50

53

1.19 [0.81, 1.74]

0.39

22%

 LPT109096

63

31

32

1.20 [0.89, 1.62]

0.23

0%

 NeoALTTO

297

149

148

1.04 [0.76, 1.41]

0.82

0%

 NSABP B-41

351

173

178

1.27 [0.87, 1.85]

0.22

18%

 TRIO-US B07

92

58

34

1.16 [0.85, 1.57]

0.35

23%

 Pooled estimate

906

461

445

1.16 [0.86, 1.56]

0.33

0%

Neutropenia (L vs. T)

 CEREBEL

536

269

267

1.01 [0.91, 1.11]

0.86

64%

 EORTC 10054

75

22

53

0.98 [0.89, 1.09]

0.76

65%

 GeparQuinto

615

308

307

1.17 [0.88, 1.56]

0.28

61%

 LPT109096

66

34

32

1.00 [0.90, 1.10]

0.98

62%

 NeoALTTO

299

151

148

0.92 [0.83, 1.02]

0.10

0%

 NSABP B-41

351

173

178

0.99 [0.89, 1.09]

0.82

65%

 TRIO-US B07

70

36

34

0.99 [0.89, 1.09]

0.78

65%

 WJOG6110B/ELTOP

86

43

43

0.99 [0.90, 1.10]

0.87

65%

 Pooled estimate

2098

1036

1062

0.99 [0.89, 1.09]

0.82

59%

Fatigue (T+L vs. T)

 CHER-Lob

82

46

36

0.73 [0.34, 1.57]

0.42

0%

 EORTC 10054

103

50

53

0.95 [0.46, 1.94]

0.88

0%

 NSABP B-41

351

173

178

0.87 [0.30, 2.48]

0.79

0%

 TRIO-US B07

92

58

34

0.84 [0.40, 1.76]

0.64

0%

 Pooled estimate

628

327

301

0.84 [0.42, 1.67]

0.62

0%

Fatigue (L vs. T)

 CEREBEL

536

269

267

1.43 [0.95, 2.15]

0.09

0%

 CHER-Lob

75

39

36

1.44 [0.97, 2.14]

0.07

0%

 EORTC 10054

75

22

53

1.41 [0.95, 2.09]

0.09

0%

 GeparQuinto

615

308

307

1.45 [0.83, 2.54]

0.20

0%

 NSABP B-41

351

173

178

1.47 [0.94, 2.29]

0.09

0%

 TRIO-US B07

70

36

34

1.44 [0.97, 2.14]

0.07

0%

 Pooled estimate

1722

847

875

1.44 [0.97, 2.11]

0.07

0%

Rash/Skin toxicity (T+L vs. T)

 ALTTO

4137

2061

2076

5.75 [3.57, 9.24]

<0.00001

0%

 ALTTOa

4152

2076

2076

6.80 [4.25, 10.87]

<0.00001

11%

 CALGB 40601

235

117

118

6.66 [4.54, 9.77]

<0.00001

9%

 CHER-Lob

82

46

36

7.11 [4.85, 10.44]

<0.00001

0%

 EORTC 10054

103

50

53

7.08 [4.84, 10.38]

<0.00001

0%

 NeoALTTO

297

149

148

6.74 [4.63, 9.82]

<0.00001

11%

 NSABP B-41

351

173

178

6.77 [4.66, 9.84]

<0.00001

10%

 Pooled estimate

9357

4672

4685

6.75 [4.66, 9.77]

<0.00001

0%

Rash/Skin toxicity (L vs. T)

 ALTTO

4133

2057

2076

6.45 [3.38, 12.29]

<0.00001

0%

 CALGB 40601

182

64

118

8.67 [5.51, 13.65]

<0.00001

0%

 CEREBEL

536

269

267

8.93 [5.73, 13.93]

<0.00001

0%

 CHER-Lob

75

39

36

9.33 [5.91, 14.72]

<0.00001

0%

 EORTC 10054

75

22

53

9.31 [5.94, 14.58]

<0.00001

0%

 GeparQuinto

615

308

307

8.48 [5.37, 13.38]

<0.00001

0%

 NeoALTTO

299

151

148

8.75 [5.61, 13.65]

<0.00001

0%

 NSABP B-41

351

173

178

8.55 [5.51, 13.28]

<0.00001

0%

 WJOG6110B/ELTOP

86

43

43

8.75 [5.63, 13.58]

<0.00001

0%

 Pooled estimate

6352

3126

3226

8.71 [5.64, 13.45]

<0.00001

0%

Vomiting (T+L vs. T)

 CHER-Lob

82

46

36

2.27 [0.80, 6.44]

0.12

0%

 EORTC 10054

103

50

53

2.10 [0.85, 5.19]

0.11

0%

 LPT109096

63

31

32

2.11 [0.85, 5.21]

0.11

0%

 NSABP B-41

351

173

178

2.31 [0.64, 8.37]

0.20

0%

 Pooled estimate

599

300

299

2.17 [0.91, 5.19]

0.08

0%

Vomiting (L vs. T)

 CEREBEL

536

269

267

1.39 [0.68, 2.84]

0.37

0%

 CHER-Lob

75

39

36

1.28 [0.65, 2.53]

0.48

0%

 EORTC 10054

75

22

53

1.29 [0.69, 2.43]

0.42

0%

 GeparQuinto

615

308

307

1.56 [0.73, 3.33]

0.25

0%

 LPT109096

66

34

32

1.24 [0.65, 2.38]

0.51

0%

 NSABP B-41

351

173

178

1.05 [0.49, 2.26]

0.89

0%

 Pooled estimate

1718

845

873

1.29 [0.69, 2.43]

0.42

0%

Nausea (T+L vs. T)

 CHER-Lob

82

46

36

1.45 [0.46, 4.55]

0.52

12%

 EORTC 10054

103

50

53

2.33 [0.80, 6.76]

0.12

0%

 LPT109096

63

31

32

1.50 [0.57, 3.96]

0.41

7%

 NSABP B-41

351

173

178

1.24 [0.40, 3.91]

0.71

0%

 Pooled estimate

599

300

299

1.61 [0.64, 4.06]

0.31

0%

Nausea (L vs. T)

 CEREBEL

536

269

267

1.03 [0.56, 1.89]

0.94

0%

 CHER-Lob

75

39

36

0.98 [0.54, 1.80]

0.96

0%

 EORTC 10054

75

22

53

0.94 [0.52, 1.72]

0.85

0%

 GeparQuinto

615

308

307

1.43 [0.60, 3.37]

0.42

0%

 LPT109096

66

34

32

1.02 [0.58, 1.80]

0.94

0%

 NSABP B-41

351

173

178

0.97 [0.53, 1.77]

0.92

0%

 Pooled estimate

1718

845

873

1.02 [0.58, 1.80]

0.94

0%