supplemental digital content

Page 33 of 35 SUPPLEMENTAL DIGITAL CONTENT

Supplemental Digital Content 1. Table that reports the time-to-event outcomes in pemetrexed/carboplatin- and docetaxel/carboplatin-treated patients in the intention-to- treat population.

Supplemental Digital Content 2. Table that reports the frequency of clinically important drug-related treatment-emergent adverse events of grade 3 or 4 toxicity in the intention- to-treat population.

SUPPLEMENTAL DIGITAL CONTENT 1

TABLE. Time-to-event Outcomes in Pemetrexed/Carboplatin-treated and Docetaxel/Carboplatin- treated Patients in the ITT population

Outcome Unadjusted HR^a (95% CI) Adjusted HR^b (95% CI)

Pem/Carb vs Doc/Carb

p Pem/Carb vs

Doc/Carb

p

SWT, grade 3 or 4 toxicity^c 0.48 (0.36-0.62) < 0.001

0.48 (0.36-0.63) < 0.001

OS 0.95 (0.70-1.30) 0.760 0.92 (0.67-1.25) 0.587

PFS 0.91 (0.70-1.20) 0.519 0.88 (0.66-1.15) 0.345

a Calculated using unadjusted Cox proportional hazard models.

b Cox proportional hazard models were adjusted for the following baseline covariates: gender;

country of origin (East Asian vs other); smoking status (never vs ever); disease stage (IIIB vs IV);

and Eastern Cooperative Oncology Group (ECOG) performance status (0 or 1 vs 2).

c Classified according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.³¹

Carb, carboplatin; CI, confidence interval; Doc, docetaxel; HR, hazard ratio; Pem, pemetrexed; OS, overall survival; PFS, progression-free survival; ITT, intention-to-treat population (all randomized 1

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Page 34 of 35 patients who received at least one dose of the study drug assigned at randomization); SWT, survival without treatment-emergent toxicity.

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Page 35 of 35 SUPPLEMENTAL DIGITAL CONTENT 2

TABLE. Frequency (n, %) of Clinically Important, Drug-related^a Treatment-emergent Adverse Events of Grade 3 or 4 Toxicity^b in the ITT population

Treatment-emergent Adverse Event

Pem/Carb (N = 118)

Doc/Carb (N = 127)

p

Hematologic events

Neutropenia 38 (32.2) 80 (60.3) < 0.001

Leukopenia 20 (16.9) 49 (38.6) < 0.001

Anemia 16 (13.6) 2 (1.6) < 0.001

Thrombocytopenia 11 (9.3) 3 (2.4) 0.026

Febrile neutropenia 0 (0.0) 11 (8.7) < 0.001

Non-hematologic events

Diarrhea 1 (0.8) 4 (3.1) 0.372

Peripheral sensory neuropathy 3 (2.5) 2 (1.6) 0.674

Vomiting 1 (0.8) 2 (1.6) 1.000

Nausea 1 (0.8) 1 (1.8) 1.000

Stomatitis 1 (0.8) 0 (0.0) 0.482

a Considered by the investigator to be possibly related to the patient’s study treatment.

b Classified according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.³¹

Carb, carboplatin; Doc, docetaxel; Pem, pemetrexed.

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