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Table 2 Clinical trials in terms of the predictive value of RAS mutational status to treatment response

From: Emerging strategies to target RAS signaling in human cancer therapy

Study

No. Total

No. Mut

Tumor stage

Treat

OS (mon)

HR (95%CI)

P

PFS (mon)

HR (95%CI)

P

References

Targeted therapy

Lievre, A., et al

89

24

mCRC

Cetuximab for KMP vs KWP

10.1 vs 14.3

ND

.026

2.4 vs 7.3

ND

.0001

[11]

NCT00079066

572

164

mCRC

Cetuximab + BSC vs BSC For KMP

4.5 vs 4.6

0.98 (0.70–1.37)

.89

1.8 vs 1.8

0.99 (0.73–1.35)

.96

[211]

Amado, R. G., et al

427

184

mCRC

Panitumumab + BSC vs BSC For KMP

4.9 vs 4.4

1.02 (0.75–1.39)

ND

1.7 vs 1.7

0.99 (0.73–1.36)

ND

[212]

OPUS

337

99

mCRC

Cetuximab + FOLFOX4 vs FOLFOX4 for KMP

NA

ND

ND

5.5 vs 8.6

1.83 (1.10–3.05)

.0192

[213]

NCT00154102

1198

397

mCRC

Cetuximab + FOLFIRI vs FOLFIRI for KMP

16.2 vs 16.7

1.035 (0.834–1.284)

.75

7.4 vs 7.7

1.17 (.887–1.544)

.26

[214]

NCT00364013

1096

440

mCRC

Panitumumab + FOLFOX4 vs FOLFOX4 for KMP and NMP

15.6 vs 19.2

1.25 (1.02–1.55)

.03

7.3 vs 8

1.31 (1.07–1.60)

ND

[41]

NCT00339183

1083

486

mCRC

Panitumumab + FOLFIRI vs FOLFIRI for KMP

11.8 vs 11.1

ND

ND

5.0 vs 4.9

ND

.14

[215]

NCT00145314

1064

195

mCRCIV

Cetuximab + FLOX vs FLOX KMP for KMP

21.1 vs 20.4

1.03 (0.68–1.57)

.89

9.2 vs 7.8

0.71 (0.50–1.03)

.07

[216]

NCT01000025

720

78

NSCLC IV

Dacomitinib vs placebo for KMP

5.82 vs 8.28

2.10 (1.05–4.22)

NA

1.61 vs 1.86

1.34 (0.78–2.29)

ND

[217]

NCT00637910

219

51

NSCLC IV

Docetaxel vs Erlotinib for KMP

NA

0.81 (0.45–1.47)

ND

NA

0.89 (0.51–1.57)

ND

[218, 219]

TRIBUTE

274

55

NSCLC IIIB or IV

Erlotinib + CP vs CP for KMP

4.4 vs 13.5

NA

.019

NA

ND

ND

[44]

TRUST

311

17

NSCLC IIIB or IV

Erlotinib for KMP vs KWP

NA

1.64 (0.97–2.80)

.064

NA

1.56 (0.92–2.65)

.094

[220]

NCIC CTG PA.3

569

92

aPC

Erlotinib + Gem vs placebo + Gem for KMP

6.0 vs 7.4

1.07 (0.68–1.66)

.78

NA

ND

ND

[221, 222]

NCT00440167

281

121

aPC

Gem + Erlotinib/Cap or Cap + Erlotinib/Gem for KWP vs KMP

7.9 vs 5.7

1.68 (1.17–2.41)

.005

NA

ND

ND

[223]

NCT01267344

122

44

aBTC

Gem, Ox + Cetuximab vs Gem, Ox For KMP

NA

0.73 (0.39–1.35)

.313

NA

ND

ND

[224]

Chemotherapy

CALGB 89803

508

178

CRC III

FU/LV or IFL for KMP vs KWP

NA

0.86 (0.60–1.23)

ND

NA

0.95 (0.70–1.28)

ND

[225]

TRIBUTE

274

55

NSCLC IIIB or IV

CP for KMP vs KWP

13.5 vs 11.3

ND

ND

NA

ND

ND

[44]

OPUS

337

99

mCRC

FOLFOX4 for KMP vs KWP

NA

ND

ND

8.6 vs 7.2

1.404 (0.867–2.271)

ND

[213]

  1. KMP KRAS-mutant patients, NMP NRAS-mutant patients, KWP wild-type KRAS patients, BSC best supportive care, mCRC metastatic colorectal cancer, NSCLC non-small-cell lung carcinoma, aPC advanced pancreatic cancer, aBTC advanced biliary tract cancer, FOLFOX4 oxaliplatin, fluorouracil, and leucovorin, FOLFIRI 5-fluorouracil, folinic acid, and irinotecan, Gem gemcitabine, CP carboplatin and paclitaxel, Cap capecitabine, Ox oxaliplatin, IFL fluorouracil [5-FU], leucovorin, and irinotecan, FU/LV 5FU + leucovorin, NA none, ND not determined