Supplementary appendix - The Lancet

Supplementary appendix This appendix formed part of the original submission and has been peer reviewed. We post it as supplied by the authors. Supplement to: Garon EB, Ciuleanu T-E, Arrieta O, et al. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Lancet 2014; published online June 2. http://dx.doi.org/10.1016/S0140-6736(14)60845-X.

 

SUPPLEMENTARY APPENDIX Supplement to: Ramucirumab-Docetaxel versus Placebo-Docetaxel for Second-line Treatment of Stage IV Non-Small Cell Lung Cancer Following Disease Progression after Platinum-Based Therapy (REVEL): a Global, Randomised Phase 3 Trial

Table of Contents

Page number

Table 1S. Subsequent systemic antineoplastic therapy

2

Table 2S. Objective tumour response for ITT population and nonsquamous and squamous subgroups

3

Table 3S. Pre-specified sensitivity analyses of the primary and key secondary endpoints in the ITT patient population.

4

Table 4S. Multivariable Cox regression analysis of overall survival time

5

Table 5S. Multivariable Cox regression analysis of progression-free survival

6

Table 6S. Dose delivery

7

Table 7S. Adverse events of special interest by NSCLC histology subtype, regardless of causality

8

Figure 1S. Kaplan-Meier estimates of overall survival for histology subgroups

10

Figure 2S. Kaplan-Meier estimates of progression-free survival for histology subgroups

12

Figure 3S. Forest plot for subgroup analyses of overall survival and progression-free survival in the two study arms

14

Figure 4S. Kaplan-Meier time to deterioration for LCSS by treatment group

16

Inclusion and exclusion criteria

17

Dose reduction scheme

21

Interim futility analysis

22

Preplanned subgroups for analysis

22

List of investigators

23

1    

  Table 1S. Subsequent systemic antineoplastic therapy. Ramucirumab-Docetaxel Arm (N=628)

Placebo-Docetaxel Arm (N=625)

n

(%)

n

(%)

Patients with at least 1 post-discontinuation therapy

320

(51·0)

343

(54·9)

Radiotherapy (adjuvant, neoadjuvant, or palliative)

99

(15·8)

103

(16·5)

Surgery (curative or palliative)

8

(1·3)

11

(1·8)

285

(45·4)

302

(48·3)

EGFR TKI

118

(18·8)

133

(21·3)

Gemcitabine

77

(12·3)

73

(11·7)

Vinorelbine

59

(9·4)

64

(10·2)

Pemetrexed

66

(10·5)

46

(7·4)

Platinum

58

(9·2)

49

(7·8)

Taxanes

38

(6·1)

45

(7·2)

Bevacizumab

12

(1·9)

9

(1·4)

Alk inhibitor

6

(1·0)

6

(1·0)

Systemic therapy (adjuvant, neoadjuvant, maintenance, palliative)

Abbreviations: Alk inhibitor=anaplastic lymphoma kinase inhibitor; EGFR TKI= epidermal growth factor receptor tyrosine kinase inhibitor

2    

  Table 2S. Objective tumour response for ITT population and nonsquamous and squamous subgroups. ITT Population

Ramucirumab-Docetaxel Arm (N=628)

Placebo-Docetaxel Arm (N=625)

n

(%)

n

(%)

3

(0·5)

2

(0·3)

Partial response (PR)

141

(22·5)

83

(13·3)

Stable disease (SD)

258

(41·1)

244

(39·0)

Progressive disease

128

(20·4)

206

(33·0)

Unknown / Not assessed

98

(15·6)

90

(14·4)

144

(22·9)

85

(13·6)

P-value*

Best Overall Response Complete response (CR)

Objective Response rate: CR + PR (95% CI) Disease control rate: CR + PR + SD

(19·7, 26·4) 402

(95% CI) Nonsquamous subpopulation