Table 3 Open in new tab Summary of the...

		KRAS exons 2, 3, and 4 wild type	KRAS exons 2,3,4 mutation
Adelstein [40] (n = 8,924)	P/C vs. SOC or P/C + SOC vs. SOC Interaction: KRASwt/KRASmt	0.80 [0.64–0.99] 0.71 [0.57–0.90]	n.d.	1.11 [0.97–1.27]	n.d.
Dahabreh [41] (n=1,945)	P/C +‐ SOC vs. BSC or SOC Interaction: KRASmt/KRASwt	n.d.	n.d.	n.d. 2.22 [1.74–2.55]	n.d. 1.30 [0.95–1.78]
Lin [42] (n = 5,325)	P/C +SOC vs. SOC	0.66 [0.53–0.82]	n.d.	1.07 [0.91–1.27]	n.d.
Loupakis [43] (n = 6,609)	P/C+ SOC vs. SOC	0.91 [0.84–0.99]	0.95 [0.87–1.04]	1.13 [1.03–1.25]	1.04 [0.95–1.13]
Petrelli [44] (n = 484)	P/C+ SOC vs. SOC	0.68 [0.53–0.87]	0.88 [0.65–1.20]	n.d.	n.d.
Petrelli [45] (n = 3,254)	P/C+ SOC vs. SOC	0.65 [0.51–0.83]	0.84 [0.73–0.98]	n.d.	n.d.
Qiu [46] (n = 2,188)	C + SOC vs. SOC Interaction: KRASmt/KRASwt	5.8 1.94 [1.62–2.33]	6.9 2.17 [1.72–2.74]	3.0	13.5
Vale [47] (n = 5,966)	P/C+ SOC vs. SOC Interaction: KRASwt/KRASmt	0.83 [0.76–0.90] 0.78 [0.68–0.89]	0.89 [0.82–0.97] 1.04 [0.95–1.15]	1.06 [0.96–1.17]	1.04 [0.95–1.15]
Zhang [48] (n = 2,912)	P/C+ SOC vs. SOC	0.64 [0.50–0.84]	0.84 [0.64–1.11]	1.37 [0.81–2.31]	1.03 [0.74–1.44]
Ibrahim [49] (n = 2,115)	P + SOC vs. SOC	0.58 [0.36–0.93]	0.90 [0.76–1.05]	n.d.	n.d.

KRAS exons 2, 3, and 4 wild type

KRAS exons 2,3,4 mutation

Study [Ref] (n)

Treatment

HR PFS

HR OS

HR PFS

HR OS

Adelstein [40] (n = 8,924)

P/C vs. SOC or

P/C + SOC vs. SOC

Interaction: KRASwt/KRASmt

0.80 [0.64–0.99]

0.71 [0.57–0.90]

n.d.

1.11 [0.97–1.27]

n.d.

Dahabreh [41]

(n=1,945)

P/C +‐ SOC vs.

BSC or SOC

Interaction: KRASmt/KRASwt

n.d.

2.22

[1.74–2.55]

n.d.

1.30

[0.95–1.78]

Lin [42]

(n = 5,325)

P/C +SOC vs. SOC

0.66 [0.53–0.82]

n.d.

1.07 [0.91–1.27]

n.d.

Loupakis [43] (n = 6,609)

P/C+ SOC vs. SOC

0.91

[0.84–0.99]

0.95

[0.87–1.04]

1.13

[1.03–1.25]

1.04

[0.95–1.13]

Petrelli [44]

(n = 484)

P/C+ SOC vs. SOC

0.68

[0.53–0.87]

0.88

[0.65–1.20]

n.d.

Petrelli [45]

(n = 3,254)

P/C+ SOC vs. SOC

0.65

[0.51–0.83]

0.84

[0.73–0.98]

n.d.

Qiu [46]

(n = 2,188)

C + SOC vs. SOC

Interaction: KRASmt/KRASwt

5.8

1.94

[1.62–2.33]

6.9

2.17

[1.72–2.74]

3.0

13.5

Vale [47]

(n = 5,966)

P/C+ SOC vs. SOC

Interaction: KRASwt/KRASmt

0.83

[0.76–0.90]

0.78

[0.68–0.89]

0.89

[0.82–0.97]

1.04

[0.95–1.15]

1.06

[0.96–1.17]

1.04

[0.95–1.15]

Zhang [48]

(n = 2,912)

P/C+ SOC vs. SOC

0.64

[0.50–0.84]

0.84

[0.64–1.11]

1.37

[0.81–2.31]

1.03

[0.74–1.44]

Ibrahim [49]

(n = 2,115)

P + SOC vs. SOC

0.58

[0.36–0.93]

0.90

[0.76–1.05]

n.d.

		KRAS exons 2, 3, and 4 wild type	KRAS exons 2,3,4 mutation
Adelstein [40] (n = 8,924)	P/C vs. SOC or P/C + SOC vs. SOC Interaction: KRASwt/KRASmt	0.80 [0.64–0.99] 0.71 [0.57–0.90]	n.d.	1.11 [0.97–1.27]	n.d.
Dahabreh [41] (n=1,945)	P/C +‐ SOC vs. BSC or SOC Interaction: KRASmt/KRASwt	n.d.	n.d.	n.d. 2.22 [1.74–2.55]	n.d. 1.30 [0.95–1.78]
Lin [42] (n = 5,325)	P/C +SOC vs. SOC	0.66 [0.53–0.82]	n.d.	1.07 [0.91–1.27]	n.d.
Loupakis [43] (n = 6,609)	P/C+ SOC vs. SOC	0.91 [0.84–0.99]	0.95 [0.87–1.04]	1.13 [1.03–1.25]	1.04 [0.95–1.13]
Petrelli [44] (n = 484)	P/C+ SOC vs. SOC	0.68 [0.53–0.87]	0.88 [0.65–1.20]	n.d.	n.d.
Petrelli [45] (n = 3,254)	P/C+ SOC vs. SOC	0.65 [0.51–0.83]	0.84 [0.73–0.98]	n.d.	n.d.
Qiu [46] (n = 2,188)	C + SOC vs. SOC Interaction: KRASmt/KRASwt	5.8 1.94 [1.62–2.33]	6.9 2.17 [1.72–2.74]	3.0	13.5
Vale [47] (n = 5,966)	P/C+ SOC vs. SOC Interaction: KRASwt/KRASmt	0.83 [0.76–0.90] 0.78 [0.68–0.89]	0.89 [0.82–0.97] 1.04 [0.95–1.15]	1.06 [0.96–1.17]	1.04 [0.95–1.15]
Zhang [48] (n = 2,912)	P/C+ SOC vs. SOC	0.64 [0.50–0.84]	0.84 [0.64–1.11]	1.37 [0.81–2.31]	1.03 [0.74–1.44]
Ibrahim [49] (n = 2,115)	P + SOC vs. SOC	0.58 [0.36–0.93]	0.90 [0.76–1.05]	n.d.	n.d.

Table 3

Open in new tab

Summary of the data from meta‐analyses addressing the effect of KRAS exons 2, 3, and 4 mutations referred to in the American Society of Clinical Oncology's clinical opinion update 2015 [1]

		KRAS exons 2, 3, and 4 wild type		KRAS exons 2,3,4 mutation
Study [Ref] (n)	Treatment	HR PFS	HR OS	HR PFS	HR OS
Adelstein [40] (n = 8,924)	P/C vs. SOC or P/C + SOC vs. SOC Interaction: KRASwt/KRASmt	0.80 [0.64–0.99] 0.71 [0.57–0.90]	n.d.	1.11 [0.97–1.27]	n.d.
Dahabreh [41] (n=1,945)	P/C +‐ SOC vs. BSC or SOC Interaction: KRASmt/KRASwt	n.d.	n.d.	n.d. 2.22 [1.74–2.55]	n.d. 1.30 [0.95–1.78]
Lin [42] (n = 5,325)	P/C +SOC vs. SOC	0.66 [0.53–0.82]	n.d.	1.07 [0.91–1.27]	n.d.
Loupakis [43] (n = 6,609)	P/C+ SOC vs. SOC	0.91 [0.84–0.99]	0.95 [0.87–1.04]	1.13 [1.03–1.25]	1.04 [0.95–1.13]
Petrelli [44] (n = 484)	P/C+ SOC vs. SOC	0.68 [0.53–0.87]	0.88 [0.65–1.20]	n.d.	n.d.
Petrelli [45] (n = 3,254)	P/C+ SOC vs. SOC	0.65 [0.51–0.83]	0.84 [0.73–0.98]	n.d.	n.d.
Qiu [46] (n = 2,188)	C + SOC vs. SOC Interaction: KRASmt/KRASwt	5.8 1.94 [1.62–2.33]	6.9 2.17 [1.72–2.74]	3.0	13.5
Vale [47] (n = 5,966)	P/C+ SOC vs. SOC Interaction: KRASwt/KRASmt	0.83 [0.76–0.90] 0.78 [0.68–0.89]	0.89 [0.82–0.97] 1.04 [0.95–1.15]	1.06 [0.96–1.17]	1.04 [0.95–1.15]
Zhang [48] (n = 2,912)	P/C+ SOC vs. SOC	0.64 [0.50–0.84]	0.84 [0.64–1.11]	1.37 [0.81–2.31]	1.03 [0.74–1.44]
Ibrahim [49] (n = 2,115)	P + SOC vs. SOC	0.58 [0.36–0.93]	0.90 [0.76–1.05]	n.d.	n.d.

		KRAS exons 2, 3, and 4 wild type		KRAS exons 2,3,4 mutation
Study [Ref] (n)	Treatment	HR PFS	HR OS	HR PFS	HR OS
Adelstein [40] (n = 8,924)	P/C vs. SOC or P/C + SOC vs. SOC Interaction: KRASwt/KRASmt	0.80 [0.64–0.99] 0.71 [0.57–0.90]	n.d.	1.11 [0.97–1.27]	n.d.
Dahabreh [41] (n=1,945)	P/C +‐ SOC vs. BSC or SOC Interaction: KRASmt/KRASwt	n.d.	n.d.	n.d. 2.22 [1.74–2.55]	n.d. 1.30 [0.95–1.78]
Lin [42] (n = 5,325)	P/C +SOC vs. SOC	0.66 [0.53–0.82]	n.d.	1.07 [0.91–1.27]	n.d.
Loupakis [43] (n = 6,609)	P/C+ SOC vs. SOC	0.91 [0.84–0.99]	0.95 [0.87–1.04]	1.13 [1.03–1.25]	1.04 [0.95–1.13]
Petrelli [44] (n = 484)	P/C+ SOC vs. SOC	0.68 [0.53–0.87]	0.88 [0.65–1.20]	n.d.	n.d.
Petrelli [45] (n = 3,254)	P/C+ SOC vs. SOC	0.65 [0.51–0.83]	0.84 [0.73–0.98]	n.d.	n.d.
Qiu [46] (n = 2,188)	C + SOC vs. SOC Interaction: KRASmt/KRASwt	5.8 1.94 [1.62–2.33]	6.9 2.17 [1.72–2.74]	3.0	13.5
Vale [47] (n = 5,966)	P/C+ SOC vs. SOC Interaction: KRASwt/KRASmt	0.83 [0.76–0.90] 0.78 [0.68–0.89]	0.89 [0.82–0.97] 1.04 [0.95–1.15]	1.06 [0.96–1.17]	1.04 [0.95–1.15]
Zhang [48] (n = 2,912)	P/C+ SOC vs. SOC	0.64 [0.50–0.84]	0.84 [0.64–1.11]	1.37 [0.81–2.31]	1.03 [0.74–1.44]
Ibrahim [49] (n = 2,115)	P + SOC vs. SOC	0.58 [0.36–0.93]	0.90 [0.76–1.05]	n.d.	n.d.

All meta‐analyses included RCTs only, except for Qui [46] and Dahabrabeh et al. [41] who included also retrospective and observational studies.

Abbreviations: BSC, best supportive care; C, cetuximab; HR, hazard ratio; KRAS, Kirsten rat sarcoma viral oncogene homolog; n, number of patients; n.d., not described; OS, overall survival; P, panitumumab; PFS, progression‐free survival; RCT, randomized controlled trial; SOC, standard of care.

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