IPASS: First Line IRESSA™ Versus Carboplatin/Paclitaxel in Asia

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00322452
• Collaborator: (none)
• Enrollment: 1,329
• Locations: 56
• Arms: 2
• Duration (Months): 51
• Patients Per Site: 23.7
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The purpose of this study is to compare gefitinib with carboplatin / paclitaxel doublet chemotherapy given as first line treatment in terms of progression free survival in selected NSCLC patients with the objective of demonstrating non-inferiority.

Condition or Disease	Intervention/Treatment	Phase
Non-Small Cell Lung Cancer	Drug: Gefitinib; Drug: Carboplatin; Drug: Paclitaxel	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1329 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open Label, Randomised, Parallel Group, Multicentre, Ph III Study To Assess Efficacy, Safety & Tolerability Of Gefitinib (IRESSA™) Versus Carboplatin/Paclitaxel DC As 1st-Line Treatment In Selected Patients With Stage IIIB / IV NSCLC In Asia
• Study Start Date: Mar 1, 2006
• Actual Primary Completion Date: Apr 1, 2008
• Actual Study Completion Date: Jun 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 gefitinib	Drug: Gefitinib; oral tablet; Other Names: Iressa ZD1839
Active Comparator: 2 Carboplatin/Paclitaxel	Drug: Carboplatin; IV; Drug: Paclitaxel; IV

Outcome Measures

Primary Outcome Measures

1. Median Progression Free Survival (PFS) in Months [Tumour assessments as per RECIST were performed at baseline and then every 42 days ± 7 days from randomization until data cut off (14th April 2008).]

   PFS was defined as the interval from the date of randomization to the date of objective disease progression (as per RECIST) or the date of death (from any cause) in the absence of objective disease progression. The median PFS in months is presented here.

Secondary Outcome Measures

1. Median Overall Survival (OS) in Months at OS Data Cut Off (14th June 2010) [Following the PFS DCO on 14th April 2008 information on survival status was collected every 8 weeks.]

   Overall Survival was assessed via calculation of the time to death due to any cause. If a participant was known to have died, the time to death was defined as the time from the date of randomization to the date of death. Otherwise, a participant was censored at the last date they were known to be alive. Median Overall Survival in months is presented here.

2. Objective Tumour Response Rate According to RECIST [Tumour assessments as per RECIST were performed at baseline and then every 42 days ± 7 days from randomization until data cut off (14th April 2008).]

   Number of participants with an objective response. An objective response (OR) was defined as a patient having a best overall response of either complete response (CR) or partial response (PR) according to RECIST, confirmed at least 28 days following the date of the initial response.

3. Common Toxicity Criteria (CTC) Grade 3, 4, or 5 Neutropenia [Includes events that occurred whilst a patient was receiving first-line randomized treatment: defined as date of first dose to date of last dose +1 day for gefitinib, and date of first infusion to date of last infusion + 21 days for carboplatin/paclitaxel]

   Number of patients with a neutropenia event, identified from the lab data as a worsening in absolute neutrophil count from baseline to a CTC grade 3 or above which Based on the evaluable-for-safety population, which included all patients who received at least 1 dose of study medication (gefitinib, or carboplatin or paclitaxel).

4. Common Toxicity Criteria (CTC) Grade 3, 4, or 5 Thrombocytopenia [Includes events that occurred whilst a patient was receiving first-line randomized treatment: defined as date of first dose to date of last dose +1 day for gefitinib, and date of first infusion to date of last infusion + 21 days for carboplatin/paclitaxel]

   Number of patients with a thromboctyopenia event, identified from the lab data as a worsening in platelet count from baseline to a CTC grade 3 or above. Based on the evaluable-for-safety population, which included all patients who received at least 1 dose of study medication (gefitinib, or carboplatin or paclitaxel).

5. Common Toxicity Criteria (CTC) Grade 3, 4, or 5 Leukopenia [Includes events that occurred whilst a patient was receiving first-line randomized treatment: defined as date of first dose to date of last dose +1 day for gefitinib, and date of first infusion to date of last infusion + 21 days for carboplatin/paclitaxel]

   Number of patients with a leukopenia event, identified from the lab data as a worsening in white blood cell count from baseline to a CTC grade 3 or above. Based on the evaluable for-safety-population, which included all patients who received at least 1 dose of study medication (gefitinib, or carboplatin or paclitaxel).

6. Common Toxicity Criteria (CTC) Grade 3, 4, or 5 Anaemia [Includes events that occurred whilst a patient was receiving first-line randomized treatment: defined as date of first dose to date of last dose +1 day for gefitinib, and date of first infusion to date of last infusion + 21 days for carboplatin/paclitaxel]

   Number of patients with an anaemia event, identified from the lab data as a worsening in haemoglobin from baseline to a CTC grade 3 or above. Based on the evaluable-for-safety population, which included all patients who received at least 1 dose of study medication (gefitinib, or carboplatin or paclitaxel).

7. Neurotoxicity [Includes events that occurred whilst a patient was receiving first-line randomized treatment: defined as date of first dose to date of last dose +1 day for gefitinib, and date of first infusion to date of last infusion + 21 days for carboplatin/paclitaxel]

   Number of patients with a neurotoxicity event. Based on the evaluable-for-safety population, which included all patients who received at least 1 dose of study medication (gefitinib, or carboplatin or paclitaxel)

8. Rashes/Acnes [Includes events that occurred whilst a patient was receiving first-line randomized treatment: defined as date of first dose to date of last dose +1 day for gefitinib, and date of first infusion to date of last infusion + 21 days for carboplatin/paclitaxel]

   Number of patients with a rashes/acnes event. Based on the evaluable-for-safety population, which included all patients who received at least 1 dose of study medication (gefitinib, or carboplatin or paclitaxel)

9. Diarrhoea [Includes events that occurred whilst a patient was receiving first-line randomized treatment: defined as date of first dose to date of last dose +1 day for gefitinib, and date of first infusion to date of last infusion + 21 days for carboplatin/paclitaxel]

   Number of patients with a diarrhoea event. Based on the evaluable-for-safety population, which included all patients who received at least 1 dose of study medication (gefitinib, or carboplatin or paclitaxel)

10. Nausea [Includes events that occurred whilst a patient was receiving first-line randomized treatment: defined as date of first dose to date of last dose +1 day for gefitinib, and date of first infusion to date of last infusion + 21 days for carboplatin/paclitaxel]

    Number of patients with a nausea event. Based on the evaluable for-safety-population, which included all patients who received at least 1 dose of study medication (gefitinib, or carboplatin or paclitaxel)

11. Vomiting [Includes events that occurred whilst a patient was receiving first-line randomized treatment: defined as date of first dose to date of last dose +1 day for gefitinib, and date of first infusion to date of last infusion + 21 days for carboplatin/paclitaxel]

    Number of patients with a vomiting event. Based on the evaluable-for-safety population, which included all patients who received at least 1 dose of study medication (gefitinib, or carboplatin or paclitaxel)

12. Common Toxicity Criteria (CTC) Grade 3, 4, or 5 Liver Transaminases [Includes events that occurred whilst a patient was receiving first-line randomized treatment: defined as date of first dose to date of last dose +1 day for gefitinib, and date of first infusion to date of last infusion + 21 days for carboplatin/paclitaxel]

    Number of patients with an elevated liver transaminase event, identified from the lab data as a worsening in ALT or AST from baseline to a CTC grade 3 or above. Based on the evaluable-for-safety population, which included all patients who received at least 1 dose of study medication (gefitinib, or carboplatin or paclitaxel).

13. Quality of Life (QoL) as Measured by the Total Score of the Functional Assessment of Cancer Therapy - Lung Cancer (FACT-L) Questionnaire [FACT-L data were collected at baseline, week 1, every 3 weeks (from baseline) until day 127, then every 42 days until the patient was confirmed as having objectively progressed (via RECIST), and at treatment discontinuation.]

    Number of patients improving: a patient was described as improved if they had 2 visits (at least 21 days apart) where there was an increase in FACT-L score (from baseline) of 6 or more, and there were no intervening visits showing a decrease from baseline of 6 or more. Includes all patients with QoL data at baseline & at least 1 post-baseline visit

14. Quality of Life (QoL) as Measured by the Trial Outcome Index (TOI) of the Functional Assessment of Cancer Therapy - Lung Cancer (FACT-L) Questionnaire [FACT-L data were collected at baseline, week 1, every 3 weeks (from baseline) until day 127, then every 42 days until the patient was confirmed as having objectively progressed (via RECIST), and at treatment discontinuation.]

    Number of patients improving: a patient was described as improved if they had 2 visits (at least 21 days apart) where there was an increase in TOI score (from baseline) of 6 or more, and there were no intervening visits showing a decrease from baseline of 6 or more. Includes all patients with QoL data at baseline & at least 1 post-baseline visit

15. Symptom Improvement as Measured by the Lung Cancer Subscale (LCS) of the FACT-L Questionnaire [FACT-L data were collected at baseline, week 1, every 3 weeks (from baseline) until day 127, then every 42 days until the patient was confirmed as having objectively progressed (via RECIST), and at treatment discontinuation.]

    Number of patients improving: a patient was described as improved if they had 2 visits (at least 21 days apart) where there was an increase in LCS score (from baseline) of 2 or more, and there were no intervening visits showing a decrease from baseline of 2 or more. Includes all patients with QoL data at baseline & at least 1 post-baseline visit

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Locally advanced Stage IIIB not amenable to local therapy or Stage IV (metastatic) NSCLC with adenocarcinoma histology.

• Never smokers or light ex-smokers.(ceased smoking at least 15 years before Day 1 of study treatment and 10 pack-years or fewer)

Exclusion Criteria:

• Had prior chemotherapy, biological (including targeted therapies such as EGFR and vascular epidermal growth factor (VEGF) inhibitors) or immunological therapy.

• Pre-existing idiopathic pulmonary fibrosis evidence by CT scan at baseline.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Fuzhou	Fujian	China
2	Research Site	Guangzhou	Guangdong	China
3	Research Site	Wuhan	Hubei	China
4	Research Site	Nanjing	Jiangsu	China
5	Research Site	Dalian	Liaoning	China
6	Research Site	Chongqing	Sichuan	China
7	Research Site	Beijing		China
8	Research Site	Chengdu		China
9	Research Site	Hangzhou		China
10	Research Site	Shanghai		China
11	Research Site	Hong Kong		Hong Kong
12	Research Site	Semarang	Central Java	Indonesia
13	Research Site	Malang	East Java	Indonesia
14	Research Site	Jakarta		Indonesia
15	Research Site	Solo		Indonesia
16	Research Site	Surabaya		Indonesia
17	Research Site	Yogyakarta		Indonesia
18	Research Site	Nagoya	Aichi	Japan
19	Research Site	Okazaki	Aichi	Japan
20	Research Site	Kashiwa	Chiba	Japan
21	Research Site	Matsuyama	Ehime	Japan
22	Research Site	Sapporo	Hokkaido	Japan
23	Research Site	Akashi	Hyogo	Japan
24	Research Site	Kobe	Hyogo	Japan
25	Research Site	Kanazawa	Ishikawa	Japan
26	Research Site	Yokohama	Kanagawa	Japan
27	Research Site	Omura	Nagasaki	Japan
28	Research Site	Izumisano	Osaka	Japan
29	Research Site	Osakasayama	Osaka	Japan
30	Research Site	Sakai	Osaka	Japan
31	Research Site	Sunto-gun	Shizuoka	Japan
32	Research Site	Bunkyo-ku	Tokyo	Japan
33	Research Site	Koto-ku	Tokyo	Japan
34	Research Site	Shinjuku	Tokyo	Japan
35	Research Site	Ube	Yamaguchi	Japan
36	Research Site	Fukuoka		Japan
37	Research Site	Kumamoto		Japan
38	Research Site	Okayama		Japan
39	Research Site	Osaka		Japan
40	Research Site	Kota Kinabalu	Sabah	Malaysia
41	Research Site	Kuala Lumpur		Malaysia
42	Research Site	Nilai		Malaysia
43	Research Site	Penang		Malaysia
44	Research Site	Petaling Jaya		Malaysia
45	Research Site	Cebu City		Philippines
46	Research Site	Manila		Philippines
47	Research Site	Quezon City		Philippines
48	Research Site	Singapore		Singapore
49	Research Site	Changhua		Taiwan
50	Research Site	Kaohsiung		Taiwan
51	Research Site	Taipei		Taiwan
52	Research Site	Tao-Yuan		Taiwan
53	Research Site	Bangkok		Thailand
54	Research Site	Chiang Mai		Thailand
55	Research Site	Khon Kaen		Thailand
56	Research Site	Songkla		Thailand

Sponsors and Collaborators

• AstraZeneca

Investigators

• Study Director: Alison Armour, MD, AstraZeneca

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT00322452
• Other Study ID Numbers: D791AC00007; Iressa Pan Asian Study (IPASS)
• First Posted: May 8, 2006
• Last Update Posted: Nov 7, 2013
• Last Verified: Oct 1, 2013

• Keywords provided by AstraZeneca: NSCLC; Gefitinib
• Additional relevant MeSH terms: Carcinoma, Non-Small-Cell Lung; Paclitaxel; Carboplatin; Gefitinib

Study Results

Participant Flow

Recruitment Details	Males or females that had never smoked or were light ex-smokers, who had Stage IIIB or Stage IV adenocarcinoma of the lung and had not received any previous chemotherapy excluding non-platinum based adjuvant chemotherapy were randomised between 30 March 2006 and 9 October 2007. The study was carried out in Asian countries (including Japan & China).
Pre-assignment Detail	112 patients (out of 1329) failed screening and were not randomized, the majority of patients who failed screening did not comply with inclusion / exclusion criteria. Other reasons were: patient withdrew informed consent; patient lost to follow up. One patient was not randomized for 'other' (non-specified) reason.

Arm/Group Title	Gefitinib	Carboplatin/Paclitaxel
Arm/Group Description	Gefitinib 250mg daily	Carboplatin AUC 5.0 or 6.0 and Paclitaxel 200 mg/m^2 doublet chemotherapy every 3 weeks
Period Title: Overall Study
STARTED	609	608
COMPLETED	362	332
NOT COMPLETED	247	276

Baseline Characteristics

Arm/Group Title	Gefitinib	Carboplatin/Paclitaxel	Total
Arm/Group Description	Gefitinib 250mg daily	Carboplatin AUC 5.0 or 6.0 and Paclitaxel 200 mg/m^2 doublet chemotherapy every 3 weeks	Total of all reporting groups
Overall Participants	609	608	1217
Age (Years) [Median (Full Range) ]
Median (Full Range) [Years]	57	57	57
Sex: Female, Male (Count of Participants)
Female	484 79.5%	481 79.1%	965 79.3%
Male	125 20.5%	127 20.9%	252 20.7%
Race/Ethnicity, Customized (Number) [Number]
Caucasian	3 0.5%	1 0.2%	4 0.3%
Oriental	603 99%	606 99.7%	1209 99.3%
Other	3 0.5%	1 0.2%	4 0.3%
Race/Ethnicity, Customized (Number) [Number]
Asian (other than Chinese or Japanese)	179 29.4%	184 30.3%	363 29.8%
Chinese	314 51.6%	304 50%	618 50.8%
Japanese	114 18.7%	119 19.6%	233 19.1%
Other	2 0.3%	1 0.2%	3 0.2%
Smoking history (Number) [Number]
Never Smoker	571 93.8%	569 93.6%	1140 93.7%
Light ex-smoker	37 6.1%	38 6.3%	75 6.2%
Ex-smoker (non-light)	1 0.2%	1 0.2%	2 0.2%
WHO performance status (Number) [Number]
0 (normal activity)	157 25.8%	161 26.5%	318 26.1%
1 (restricted activity)	391 64.2%	382 62.8%	773 63.5%
2 (in bed =< 50% of the time)	61 10%	65 10.7%	126 10.4%

Outcome Measures

1. Primary Outcome

Title	Median Progression Free Survival (PFS) in Months
Description	PFS was defined as the interval from the date of randomization to the date of objective disease progression (as per RECIST) or the date of death (from any cause) in the absence of objective disease progression. The median PFS in months is presented here.
Time Frame	Tumour assessments as per RECIST were performed at baseline and then every 42 days ± 7 days from randomization until data cut off (14th April 2008).

Outcome Measure Data

Analysis Population Description

Analysis was carried out on Intention-to-treat (ITT) population.

Arm/Group Title	Gefitinib	Carboplatin/Paclitaxel
Arm/Group Description	Gefitinib 250mg daily	Carboplatin AUC 5.0 or 6.0 and Paclitaxel 200 mg/m^2 doublet chemotherapy every 3 weeks
Measure Participants	609	608
Median (95% Confidence Interval) [Months]	5.7	5.8

2. Secondary Outcome

Title	Median Overall Survival (OS) in Months at OS Data Cut Off (14th June 2010)
Description	Overall Survival was assessed via calculation of the time to death due to any cause. If a participant was known to have died, the time to death was defined as the time from the date of randomization to the date of death. Otherwise, a participant was censored at the last date they were known to be alive. Median Overall Survival in months is presented here.
Time Frame	Following the PFS DCO on 14th April 2008 information on survival status was collected every 8 weeks.

Outcome Measure Data

Analysis Population Description

Analysis was carried out on Intention-to-treat (ITT) population.

Arm/Group Title	Gefitinib	Carboplatin/Paclitaxel
Arm/Group Description	Gefitinib 250mg daily	Carboplatin AUC 5.0 or 6.0 and Paclitaxel 200 mg/m^2 doublet chemotherapy every 3 weeks
Measure Participants	609	608
Median (95% Confidence Interval) [Months]	18.8	17.4

3. Secondary Outcome

Title	Objective Tumour Response Rate According to RECIST
Description	Number of participants with an objective response. An objective response (OR) was defined as a patient having a best overall response of either complete response (CR) or partial response (PR) according to RECIST, confirmed at least 28 days following the date of the initial response.
Time Frame	Tumour assessments as per RECIST were performed at baseline and then every 42 days ± 7 days from randomization until data cut off (14th April 2008).

Outcome Measure Data

Analysis Population Description

Analysis was carried out on Intention-to-treat (ITT) population.

Arm/Group Title	Gefitinib	Carboplatin/Paclitaxel
Arm/Group Description	Gefitinib 250mg daily	Carboplatin AUC 5.0 or 6.0 and Paclitaxel 200 mg/m^2 doublet chemotherapy every 3 weeks
Measure Participants	609	608
Number [Participants]	262 43%	196 32.2%

4. Secondary Outcome

Title	Common Toxicity Criteria (CTC) Grade 3, 4, or 5 Neutropenia
Description	Number of patients with a neutropenia event, identified from the lab data as a worsening in absolute neutrophil count from baseline to a CTC grade 3 or above which Based on the evaluable-for-safety population, which included all patients who received at least 1 dose of study medication (gefitinib, or carboplatin or paclitaxel).
Time Frame	Includes events that occurred whilst a patient was receiving first-line randomized treatment: defined as date of first dose to date of last dose +1 day for gefitinib, and date of first infusion to date of last infusion + 21 days for carboplatin/paclitaxel

Outcome Measure Data

Analysis Population Description

Analysis was carried out on the Evaluable-for-safety (EFS) population. The EFS population is a subset of the ITT population which includes all patients who received at least 1 dose of study medication (gefitinib, or carboplatin or paclitaxel).

Arm/Group Title	Gefitinib	Carboplatin/Paclitaxel
Arm/Group Description	Gefitinib 250mg daily	Carboplatin AUC 5.0 or 6.0 and Paclitaxel 200 mg/m^2 doublet chemotherapy every 3 weeks
Measure Participants	607	589
Number [Participants]	4 0.7%	385 63.3%

5. Secondary Outcome

Title	Common Toxicity Criteria (CTC) Grade 3, 4, or 5 Thrombocytopenia
Description	Number of patients with a thromboctyopenia event, identified from the lab data as a worsening in platelet count from baseline to a CTC grade 3 or above. Based on the evaluable-for-safety population, which included all patients who received at least 1 dose of study medication (gefitinib, or carboplatin or paclitaxel).
Time Frame	Includes events that occurred whilst a patient was receiving first-line randomized treatment: defined as date of first dose to date of last dose +1 day for gefitinib, and date of first infusion to date of last infusion + 21 days for carboplatin/paclitaxel

Outcome Measure Data

Analysis Population Description

Analysis was carried out on the Evaluable-for-safety (EFS) population. The EFS population is a subset of the ITT population which includes all patients who received at least 1 dose of study medication (gefitinib, or carboplatin or paclitaxel).

Arm/Group Title	Gefitinib	Carboplatin/Paclitaxel
Arm/Group Description	Gefitinib 250mg daily	Carboplatin AUC 5.0 or 6.0 and Paclitaxel 200 mg/m^2 doublet chemotherapy every 3 weeks
Measure Participants	607	589
Number [Participants]	5 0.8%	29 4.8%

6. Secondary Outcome

Title	Common Toxicity Criteria (CTC) Grade 3, 4, or 5 Leukopenia
Description	Number of patients with a leukopenia event, identified from the lab data as a worsening in white blood cell count from baseline to a CTC grade 3 or above. Based on the evaluable for-safety-population, which included all patients who received at least 1 dose of study medication (gefitinib, or carboplatin or paclitaxel).
Time Frame	Includes events that occurred whilst a patient was receiving first-line randomized treatment: defined as date of first dose to date of last dose +1 day for gefitinib, and date of first infusion to date of last infusion + 21 days for carboplatin/paclitaxel

Outcome Measure Data

Analysis Population Description

Analysis was carried out on the Evaluable-for-safety (EFS) population. The EFS population is a subset of the ITT population which includes all patients who received at least 1 dose of study medication (gefitinib, or carboplatin or paclitaxel).

Arm/Group Title	Gefitinib	Carboplatin/Paclitaxel
Arm/Group Description	Gefitinib 250mg daily	Carboplatin AUC 5.0 or 6.0 and Paclitaxel 200 mg/m^2 doublet chemotherapy every 3 weeks
Measure Participants	607	589
Number [Participants]	1 0.2%	202 33.2%

7. Secondary Outcome

Title	Common Toxicity Criteria (CTC) Grade 3, 4, or 5 Anaemia
Description	Number of patients with an anaemia event, identified from the lab data as a worsening in haemoglobin from baseline to a CTC grade 3 or above. Based on the evaluable-for-safety population, which included all patients who received at least 1 dose of study medication (gefitinib, or carboplatin or paclitaxel).
Time Frame	Includes events that occurred whilst a patient was receiving first-line randomized treatment: defined as date of first dose to date of last dose +1 day for gefitinib, and date of first infusion to date of last infusion + 21 days for carboplatin/paclitaxel

Outcome Measure Data

Analysis Population Description

Analysis was carried out on the Evaluable-for-safety (EFS) population. The EFS population is a subset of the ITT population which includes all patients who received at least 1 dose of study medication (gefitinib, or carboplatin or paclitaxel).

Arm/Group Title	Gefitinib	Carboplatin/Paclitaxel
Arm/Group Description	Gefitinib 250mg daily	Carboplatin AUC 5.0 or 6.0 and Paclitaxel 200 mg/m^2 doublet chemotherapy every 3 weeks
Measure Participants	607	589
Number [Participants]	11 1.8%	56 9.2%

8. Secondary Outcome

Title	Neurotoxicity
Description	Number of patients with a neurotoxicity event. Based on the evaluable-for-safety population, which included all patients who received at least 1 dose of study medication (gefitinib, or carboplatin or paclitaxel)
Time Frame	Includes events that occurred whilst a patient was receiving first-line randomized treatment: defined as date of first dose to date of last dose +1 day for gefitinib, and date of first infusion to date of last infusion + 21 days for carboplatin/paclitaxel

Outcome Measure Data

Analysis Population Description

Analysis was carried out on the Evaluable-for-safety (EFS) population. The EFS population is a subset of the ITT population which includes all patients who received at least 1 dose of study medication (gefitinib, or carboplatin or paclitaxel).

Arm/Group Title	Gefitinib	Carboplatin/Paclitaxel
Arm/Group Description	Gefitinib 250mg daily	Carboplatin AUC 5.0 or 6.0 and Paclitaxel 200 mg/m^2 doublet chemotherapy every 3 weeks
Measure Participants	607	589
Number [Participants]	30 4.9%	411 67.6%

9. Secondary Outcome

Title	Rashes/Acnes
Description	Number of patients with a rashes/acnes event. Based on the evaluable-for-safety population, which included all patients who received at least 1 dose of study medication (gefitinib, or carboplatin or paclitaxel)
Time Frame	Includes events that occurred whilst a patient was receiving first-line randomized treatment: defined as date of first dose to date of last dose +1 day for gefitinib, and date of first infusion to date of last infusion + 21 days for carboplatin/paclitaxel

Outcome Measure Data

Analysis Population Description

Analysis was carried out on the Evaluable-for-safety (EFS) population. The EFS population is a subset of the ITT population which includes all patients who received at least 1 dose of study medication (gefitinib, or carboplatin or paclitaxel).

Arm/Group Title	Gefitinib	Carboplatin/Paclitaxel
Arm/Group Description	Gefitinib 250mg daily	Carboplatin AUC 5.0 or 6.0 and Paclitaxel 200 mg/m^2 doublet chemotherapy every 3 weeks
Measure Participants	607	589
Number [Participants]	398 65.4%	132 21.7%

10. Secondary Outcome

Title	Diarrhoea
Description	Number of patients with a diarrhoea event. Based on the evaluable-for-safety population, which included all patients who received at least 1 dose of study medication (gefitinib, or carboplatin or paclitaxel)
Time Frame	Includes events that occurred whilst a patient was receiving first-line randomized treatment: defined as date of first dose to date of last dose +1 day for gefitinib, and date of first infusion to date of last infusion + 21 days for carboplatin/paclitaxel

Outcome Measure Data

Analysis Population Description

Analysis was carried out on the Evaluable-for-safety (EFS) population. The EFS population is a subset of the ITT population which includes all patients who received at least 1 dose of study medication (gefitinib, or carboplatin or paclitaxel).

Arm/Group Title	Gefitinib	Carboplatin/Paclitaxel
Arm/Group Description	Gefitinib 250mg daily	Carboplatin AUC 5.0 or 6.0 and Paclitaxel 200 mg/m^2 doublet chemotherapy every 3 weeks
Measure Participants	607	589
Number [Participants]	274 45%	128 21.1%

11. Secondary Outcome

Title	Nausea
Description	Number of patients with a nausea event. Based on the evaluable for-safety-population, which included all patients who received at least 1 dose of study medication (gefitinib, or carboplatin or paclitaxel)
Time Frame	Includes events that occurred whilst a patient was receiving first-line randomized treatment: defined as date of first dose to date of last dose +1 day for gefitinib, and date of first infusion to date of last infusion + 21 days for carboplatin/paclitaxel

Outcome Measure Data

Analysis Population Description

Analysis was carried out on the Evaluable-for-safety (EFS) population. The EFS population is a subset of the ITT population which includes all patients who received at least 1 dose of study medication (gefitinib, or carboplatin or paclitaxel).

Arm/Group Title	Gefitinib	Carboplatin/Paclitaxel
Arm/Group Description	Gefitinib 250mg daily	Carboplatin AUC 5.0 or 6.0 and Paclitaxel 200 mg/m^2 doublet chemotherapy every 3 weeks
Measure Participants	607	589
Number [Participants]	74 12.2%	260 42.8%

12. Secondary Outcome

Title	Vomiting
Description	Number of patients with a vomiting event. Based on the evaluable-for-safety population, which included all patients who received at least 1 dose of study medication (gefitinib, or carboplatin or paclitaxel)
Time Frame	Includes events that occurred whilst a patient was receiving first-line randomized treatment: defined as date of first dose to date of last dose +1 day for gefitinib, and date of first infusion to date of last infusion + 21 days for carboplatin/paclitaxel

Outcome Measure Data

Analysis Population Description

Analysis was carried out on the Evaluable-for-safety (EFS) population. The EFS population is a subset of the ITT population which includes all patients who received at least 1 dose of study medication (gefitinib, or carboplatin or paclitaxel).

Arm/Group Title	Gefitinib	Carboplatin/Paclitaxel
Arm/Group Description	Gefitinib 250mg daily	Carboplatin AUC 5.0 or 6.0 and Paclitaxel 200 mg/m^2 doublet chemotherapy every 3 weeks
Measure Participants	607	589
Number [Participants]	59 9.7%	193 31.7%

13. Secondary Outcome

Title	Common Toxicity Criteria (CTC) Grade 3, 4, or 5 Liver Transaminases
Description	Number of patients with an elevated liver transaminase event, identified from the lab data as a worsening in ALT or AST from baseline to a CTC grade 3 or above. Based on the evaluable-for-safety population, which included all patients who received at least 1 dose of study medication (gefitinib, or carboplatin or paclitaxel).
Time Frame	Includes events that occurred whilst a patient was receiving first-line randomized treatment: defined as date of first dose to date of last dose +1 day for gefitinib, and date of first infusion to date of last infusion + 21 days for carboplatin/paclitaxel

Outcome Measure Data

Analysis Population Description

Analysis was carried out on the Evaluable-for-safety (EFS) population. The EFS population is a subset of the ITT population which includes all patients who received at least 1 dose of study medication (gefitinib, or carboplatin or paclitaxel).

Arm/Group Title	Gefitinib	Carboplatin/Paclitaxel
Arm/Group Description	Gefitinib 250mg daily	Carboplatin AUC 5.0 or 6.0 and Paclitaxel 200 mg/m^2 doublet chemotherapy every 3 weeks
Measure Participants	607	589
Number [Participants]	57 9.4%	6 1%

14. Secondary Outcome

Title	Quality of Life (QoL) as Measured by the Total Score of the Functional Assessment of Cancer Therapy - Lung Cancer (FACT-L) Questionnaire
Description	Number of patients improving: a patient was described as improved if they had 2 visits (at least 21 days apart) where there was an increase in FACT-L score (from baseline) of 6 or more, and there were no intervening visits showing a decrease from baseline of 6 or more. Includes all patients with QoL data at baseline & at least 1 post-baseline visit
Time Frame	FACT-L data were collected at baseline, week 1, every 3 weeks (from baseline) until day 127, then every 42 days until the patient was confirmed as having objectively progressed (via RECIST), and at treatment discontinuation.

Outcome Measure Data

Analysis Population Description

Analysis was carried out on the Evaluable-for-QoL (EFQ) population. The EFQ population is a subset of the ITT population containing patients with an evaluable baseline QoL assessment and at least 1 evaluable post-baseline QoL assessment.

Arm/Group Title	Gefitinib	Carboplatin/Paclitaxel
Arm/Group Description	Gefitinib 250mg daily	Carboplatin AUC 5.0 or 6.0 and Paclitaxel 200 mg/m^2 doublet chemotherapy every 3 weeks
Measure Participants	590	561
Number [Participants]	283 46.5%	229 37.7%

15. Secondary Outcome

Title	Quality of Life (QoL) as Measured by the Trial Outcome Index (TOI) of the Functional Assessment of Cancer Therapy - Lung Cancer (FACT-L) Questionnaire
Description	Number of patients improving: a patient was described as improved if they had 2 visits (at least 21 days apart) where there was an increase in TOI score (from baseline) of 6 or more, and there were no intervening visits showing a decrease from baseline of 6 or more. Includes all patients with QoL data at baseline & at least 1 post-baseline visit
Time Frame	FACT-L data were collected at baseline, week 1, every 3 weeks (from baseline) until day 127, then every 42 days until the patient was confirmed as having objectively progressed (via RECIST), and at treatment discontinuation.

Outcome Measure Data

Analysis Population Description

Analysis was carried out on the Evaluable-for-QoL (EFQ) population. The EFQ population is a subset of the ITT population containing patients with an evaluable baseline QoL assessment and at least 1 evaluable post-baseline QoL assessment.

Arm/Group Title	Gefitinib	Carboplatin/Paclitaxel
Arm/Group Description	Gefitinib 250mg daily	Carboplatin AUC 5.0 or 6.0 and Paclitaxel 200 mg/m^2 doublet chemotherapy every 3 weeks
Measure Participants	590	561
Number [Participants]	274 45%	184 30.3%

16. Secondary Outcome

Title	Symptom Improvement as Measured by the Lung Cancer Subscale (LCS) of the FACT-L Questionnaire
Description	Number of patients improving: a patient was described as improved if they had 2 visits (at least 21 days apart) where there was an increase in LCS score (from baseline) of 2 or more, and there were no intervening visits showing a decrease from baseline of 2 or more. Includes all patients with QoL data at baseline & at least 1 post-baseline visit
Time Frame	FACT-L data were collected at baseline, week 1, every 3 weeks (from baseline) until day 127, then every 42 days until the patient was confirmed as having objectively progressed (via RECIST), and at treatment discontinuation.

Outcome Measure Data

Analysis Population Description

Analysis was carried out on the Evaluable-for-QoL (EFQ) population. The EFQ population is a subset of the ITT population containing patients with an evaluable baseline QoL assessment and at least 1 evaluable post-baseline QoL assessment.

Arm/Group Title	Gefitinib	Carboplatin/Paclitaxel
Arm/Group Description	Gefitinib 250mg daily	Carboplatin AUC 5.0 or 6.0 and Paclitaxel 200 mg/m^2 doublet chemotherapy every 3 weeks
Measure Participants	590	561
Number [Participants]	304 49.9%	272 44.7%

Adverse Events

Arm/Group Title	Gefitinib		Carboplatin/Paclitaxel
Arm/Group Description	Gefitinib 250mg daily		Carboplatin AUC 5.0 or 6.0 and Paclitaxel 200 mg/m^2 doublet chemotherapy every 3 weeks
All Cause Mortality
	Gefitinib		Carboplatin/Paclitaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Gefitinib		Carboplatin/Paclitaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	110/607 (18.1%)		92/589 (15.6%)
Blood and lymphatic system disorders
Anaemia	1/607 (0.2%)		5/589 (0.8%)
Bone Marrow Failure	1/607 (0.2%)		0/589 (0%)
Febrile Neutropenia	1/607 (0.2%)		0/589 (0%)
Neutropenia	0/607 (0%)		10/589 (1.7%)
Cardiac disorders
Acute Myocardial Infarction	1/607 (0.2%)		1/589 (0.2%)
Angina Pectoris	1/607 (0.2%)		1/589 (0.2%)
Cardiac Arrest	0/607 (0%)		1/589 (0.2%)
Cardiac Failure	1/607 (0.2%)		0/589 (0%)
Cardio-Respiratory Arrest	1/607 (0.2%)		0/589 (0%)
Myocardial Infarction	0/607 (0%)		1/589 (0.2%)
Pericardial Effusion	1/607 (0.2%)		0/589 (0%)
Sinus Bradycardia	1/607 (0.2%)		0/589 (0%)
Ventricular Tachycardia	0/607 (0%)		1/589 (0.2%)
Ear and labyrinth disorders
Vertigo	0/607 (0%)		1/589 (0.2%)
Eye disorders
Angle Closure Glaucoma	0/607 (0%)		1/589 (0.2%)
Pupils Unequal	1/607 (0.2%)		0/589 (0%)
Gastrointestinal disorders
Abdominal Pain	1/607 (0.2%)		0/589 (0%)
Abdominal Pain Upper	1/607 (0.2%)		0/589 (0%)
Constipation	0/607 (0%)		1/589 (0.2%)
Diarrhoea	2/607 (0.3%)		2/589 (0.3%)
Duodenitis	0/607 (0%)		1/589 (0.2%)
Dyspepsia	1/607 (0.2%)		0/589 (0%)
Gastric Ulcer Perforation	1/607 (0.2%)		0/589 (0%)
Gastrointestinal Haemorrhage	2/607 (0.3%)		2/589 (0.3%)
Ileus	1/607 (0.2%)		0/589 (0%)
Nausea	0/607 (0%)		2/589 (0.3%)
Rectal Haemorrhage	1/607 (0.2%)		0/589 (0%)
Upper Gastrointestinal Haemorrhage	0/607 (0%)		1/589 (0.2%)
Vomiting	2/607 (0.3%)		6/589 (1%)
General disorders
Chest Pain	3/607 (0.5%)		0/589 (0%)
Death	1/607 (0.2%)		1/589 (0.2%)
Fatigue	0/607 (0%)		2/589 (0.3%)
Malaise	0/607 (0%)		2/589 (0.3%)
Pain	0/607 (0%)		1/589 (0.2%)
Pyrexia	3/607 (0.5%)		2/589 (0.3%)
Hepatobiliary disorders
Cholangitis	0/607 (0%)		1/589 (0.2%)
Cholecystitis	0/607 (0%)		1/589 (0.2%)
Hepatic Failure	1/607 (0.2%)		0/589 (0%)
Hepatic Function Abnormal	4/607 (0.7%)		1/589 (0.2%)
Jaundice	0/607 (0%)		1/589 (0.2%)
Immune system disorders
Anaphylactic Shock	0/607 (0%)		1/589 (0.2%)
Drug Hypersensitivity	1/607 (0.2%)		3/589 (0.5%)
Infections and infestations
Bronchitis	1/607 (0.2%)		0/589 (0%)
Bronchopneumonia	1/607 (0.2%)		0/589 (0%)
Cellulitis	1/607 (0.2%)		0/589 (0%)
Endocarditis	1/607 (0.2%)		0/589 (0%)
Gastroenteritis	2/607 (0.3%)		0/589 (0%)
Herpes Zoster	0/607 (0%)		1/589 (0.2%)
Lower Respiratory Tract Infection	1/607 (0.2%)		1/589 (0.2%)
Lung Infection	0/607 (0%)		1/589 (0.2%)
Parotitis	0/607 (0%)		1/589 (0.2%)
Pneumonia	9/607 (1.5%)		9/589 (1.5%)
Pseudomonal Sepsis	1/607 (0.2%)		0/589 (0%)
Pyothorax	2/607 (0.3%)		0/589 (0%)
Sepsis	2/607 (0.3%)		0/589 (0%)
Septic Shock	0/607 (0%)		3/589 (0.5%)
Upper Respiratory Tract Infection	1/607 (0.2%)		0/589 (0%)
Urinary Tract Infection	1/607 (0.2%)		0/589 (0%)
Urosepsis	0/607 (0%)		1/589 (0.2%)
Injury, poisoning and procedural complications
Brain Herniation	1/607 (0.2%)		0/589 (0%)
Concussion	0/607 (0%)		1/589 (0.2%)
Femur Fracture	1/607 (0.2%)		0/589 (0%)
Radius Fracture	0/607 (0%)		1/589 (0.2%)
Spinal Compression Fracture	1/607 (0.2%)		0/589 (0%)
Tibia Fracture	1/607 (0.2%)		0/589 (0%)
Investigations
Alanine Aminotransferase Increased	1/607 (0.2%)		0/589 (0%)
Blood Alkaline Phosphatase Increased	1/607 (0.2%)		0/589 (0%)
Haemoglobin Decreased	0/607 (0%)		2/589 (0.3%)
Neutrophil Count Decreased	0/607 (0%)		2/589 (0.3%)
Metabolism and nutrition disorders
Anorexia	3/607 (0.5%)		2/589 (0.3%)
Dehydration	1/607 (0.2%)		0/589 (0%)
Hyponatraemia	2/607 (0.3%)		1/589 (0.2%)
Oral Intake Reduced	0/607 (0%)		1/589 (0.2%)
Musculoskeletal and connective tissue disorders
Back Pain	2/607 (0.3%)		0/589 (0%)
Muscular Weakness	1/607 (0.2%)		1/589 (0.2%)
Musculoskeletal Pain	2/607 (0.3%)		0/589 (0%)
Osteoporotic Fracture	1/607 (0.2%)		0/589 (0%)
Pathological Fracture	0/607 (0%)		2/589 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neuroendocrine tumour	1/607 (0.2%)		0/589 (0%)
Nervous system disorders
Altered State Of Consciousness	1/607 (0.2%)		1/589 (0.2%)
Cerebral Artery Embolism	1/607 (0.2%)		0/589 (0%)
Cerebral Haemorrhage	2/607 (0.3%)		0/589 (0%)
Depressed Level Of Consciousness	1/607 (0.2%)		0/589 (0%)
Dizziness	2/607 (0.3%)		2/589 (0.3%)
Encephalitis	1/607 (0.2%)		0/589 (0%)
Hemiplegia	1/607 (0.2%)		0/589 (0%)
Iiird Nerve Paralysis	1/607 (0.2%)		0/589 (0%)
Ischaemic Stroke	1/607 (0.2%)		0/589 (0%)
Lacunar Infarction	1/607 (0.2%)		0/589 (0%)
Sciatica	1/607 (0.2%)		0/589 (0%)
Syncope Vasovagal	0/607 (0%)		1/589 (0.2%)
Renal and urinary disorders
Calculus Urinary	2/607 (0.3%)		0/589 (0%)
Haematuria	1/607 (0.2%)		0/589 (0%)
Hydronephrosis	1/607 (0.2%)		0/589 (0%)
Renal Failure Acute	1/607 (0.2%)		1/589 (0.2%)
Urinary Retention	1/607 (0.2%)		0/589 (0%)
Reproductive system and breast disorders
Dysfunctional Uterine Bleeding	1/607 (0.2%)		0/589 (0%)
Respiratory, thoracic and mediastinal disorders
Acute Pulmonary Oedema	0/607 (0%)		1/589 (0.2%)
Acute Respiratory Distress Syndrome	1/607 (0.2%)		1/589 (0.2%)
Asthma	1/607 (0.2%)		0/589 (0%)
Dyspnoea	7/607 (1.2%)		7/589 (1.2%)
Haemoptysis	0/607 (0%)		1/589 (0.2%)
Haemothorax	1/607 (0.2%)		0/589 (0%)
Hydropneumothorax	1/607 (0.2%)		0/589 (0%)
Hyperventilation	1/607 (0.2%)		0/589 (0%)
Hypoxia	0/607 (0%)		1/589 (0.2%)
Interstitial Lung Disease	6/607 (1%)		0/589 (0%)
Laryngeal Granuloma	1/607 (0.2%)		0/589 (0%)
Pleural Effusion	1/607 (0.2%)		0/589 (0%)
Pneumonitis	0/607 (0%)		1/589 (0.2%)
Pneumothorax	0/607 (0%)		2/589 (0.3%)
Pulmonary Embolism	1/607 (0.2%)		0/589 (0%)
Pulmonary Haemorrhage	1/607 (0.2%)		1/589 (0.2%)
Respiratory Failure	2/607 (0.3%)		0/589 (0%)
Vascular disorders
Deep Vein Thrombosis	1/607 (0.2%)		0/589 (0%)
Embolism	0/607 (0%)		1/589 (0.2%)
Hypotension	0/607 (0%)		1/589 (0.2%)
Other (Not Including Serious) Adverse Events
	Gefitinib		Carboplatin/Paclitaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	574/ (NaN)		573/ (NaN)
Blood and lymphatic system disorders
Anaemia	36/607 (5.9%)		146/589 (24.8%)
Leukopenia	5/607 (0.8%)		146/589 (24.8%)
Neutropenia	3/607 (0.5%)		218/589 (37%)
Thrombocytopenia	7/607 (1.2%)		70/589 (11.9%)
Gastrointestinal disorders
Constipation	47/607 (7.7%)		170/589 (28.9%)
Diarrhoea	273/607 (45%)		127/589 (21.6%)
Dyspepsia	32/607 (5.3%)		26/589 (4.4%)
Nausea	74/607 (12.2%)		259/589 (44%)
Stomatitis	78/607 (12.9%)		42/589 (7.1%)
Vomiting	58/607 (9.6%)		190/589 (32.3%)
General disorders
Fatigue	72/607 (11.9%)		217/589 (36.8%)
Pyrexia	38/607 (6.3%)		56/589 (9.5%)
Hepatobiliary disorders
Hepatic Function Abnormal	48/607 (7.9%)		23/589 (3.9%)
Infections and infestations
Nasopharyngitis	52/607 (8.6%)		22/589 (3.7%)
Paronychia	82/607 (13.5%)		0/589 (0%)
Upper Respiratory Tract Infection	34/607 (5.6%)		23/589 (3.9%)
Investigations
Alanine Aminotransferase Increased	61/607 (10%)		31/589 (5.3%)
Aspartate Aminotransferase Increased	52/607 (8.6%)		19/589 (3.2%)
Haemoglobin Decreased	1/607 (0.2%)		30/589 (5.1%)
Neutrophil Count Decreased	0/607 (0%)		39/589 (6.6%)
White Blood Cell Count Decreased	3/607 (0.5%)		52/589 (8.8%)
Metabolism and nutrition disorders
Anorexia	92/607 (15.2%)		232/589 (39.4%)
Hypokalaemia	20/607 (3.3%)		30/589 (5.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	22/607 (3.6%)		112/589 (19%)
Back Pain	32/607 (5.3%)		26/589 (4.4%)
Myalgia	24/607 (4%)		186/589 (31.6%)
Pain In Extremity	24/607 (4%)		40/589 (6.8%)
Nervous system disorders
Dizziness	31/607 (5.1%)		35/589 (5.9%)
Headache	39/607 (6.4%)		43/589 (7.3%)
Hypoaesthesia	7/607 (1.2%)		153/589 (26%)
Neuropathy Peripheral	5/607 (0.8%)		97/589 (16.5%)
Paraesthesia	8/607 (1.3%)		30/589 (5.1%)
Peripheral Sensory Neuropathy	9/607 (1.5%)		141/589 (23.9%)
Psychiatric disorders
Insomnia	72/607 (11.9%)		107/589 (18.2%)
Respiratory, thoracic and mediastinal disorders
Cough	53/607 (8.7%)		62/589 (10.5%)
Dyspnoea	35/607 (5.8%)		49/589 (8.3%)
Pharyngolaryngeal Pain	36/607 (5.9%)		28/589 (4.8%)
Skin and subcutaneous tissue disorders
Acne	66/607 (10.9%)		4/589 (0.7%)
Alopecia	42/607 (6.9%)		343/589 (58.2%)
Dermatitis Acneiform	35/607 (5.8%)		2/589 (0.3%)
Dry Skin	144/607 (23.7%)		17/589 (2.9%)
Pruritus	103/607 (17%)		69/589 (11.7%)
Rash	308/607 (50.7%)		120/589 (20.4%)
Skin Exfoliation	31/607 (5.1%)		1/589 (0.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Principal Investigator (PI) agrees to collaborate on the contents and formation of any publication and to pay due consideration to comments and opinions offered. AstraZeneca have 30 days for final manuscript review and may require that submission for publication be delayed in order to file patent applications.