Trial Outcomes & Findings for Hypofractionated Image-Guided Radiation Therapy (IGRT) in Patients With Stage II-III Non-Small Cell Lung Cancer (NCT NCT01459497)

Last Updated: 2024-01-17

Results Overview

Percentage of participants with overall survival at 1 year. To compare the efficacy by overall survival of standard radiation versus accelerated, hypofractionated, image-guided conformal radiotherapy in treatment of stage II-III or recurrent NSCLC in patients with poor performance status. Overall survival time will be estimated using the Kaplan-Meier approach. The stratified log-rank test will be used to test for a statistically significant difference in survival distributions. The Cox proportional hazard regression model will be used to determine hazard ratios and 95% confidence intervals for the treatment difference in overall survival. Unadjusted ratios and ratios adjusted for stratification variables and other covariates of interest will be computed.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

103 participants

Primary outcome timeframe

1 year

Results posted on

2024-01-17

Participant Flow

Participant milestones

Participant milestones
Measure	Radiation Therapy Arm A:Image-Guided Radiation Therapy (IGRT), 60 Gy in 15 fractions in 3 weeks Radiation Therapy: Image-Guided Radiation Therapy (IGRT)60 Gy in 15 fractions in 3 weeks	Conventional Radiation Arm B: Conventional radiation 60-66 Gy in 30-33 fractions in 6-7 weeks Conventional radiation: Conventional radiation 60-66 Gy in 30-33 fractions in 6-7 weeks
Overall Study STARTED	52	51
Overall Study COMPLETED	50	46
Overall Study NOT COMPLETED	2	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Radiation Therapy Arm A:Image-Guided Radiation Therapy (IGRT), 60 Gy in 15 fractions in 3 weeks Radiation Therapy: Image-Guided Radiation Therapy (IGRT)60 Gy in 15 fractions in 3 weeks	Conventional Radiation Arm B: Conventional radiation 60-66 Gy in 30-33 fractions in 6-7 weeks Conventional radiation: Conventional radiation 60-66 Gy in 30-33 fractions in 6-7 weeks
Overall Study Inability to meet trial constraints.	1	0
Overall Study Physician Decision	1	1
Overall Study Hospitalization.	0	3
Overall Study Disease progression.	0	1

Baseline Characteristics

Hypofractionated Image-Guided Radiation Therapy (IGRT) in Patients With Stage II-III Non-Small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Radiation Therapy n=50 Participants Arm A:Image-Guided Radiation Therapy (IGRT), 60 Gy in 15 fractions in 3 weeks Radiation Therapy: Image-Guided Radiation Therapy (IGRT)60 Gy in 15 fractions in 3 weeks	Conventional Radiation n=46 Participants Arm B: Conventional radiation 60-66 Gy in 30-33 fractions in 6-7 weeks Conventional radiation: Conventional radiation 60-66 Gy in 30-33 fractions in 6-7 weeks	Total n=96 Participants Total of all reporting groups
Age, Customized Ages 50-59 years	6 Participants n=5 Participants	9 Participants n=7 Participants	15 Participants n=5 Participants
Age, Customized Ages 60-69 years	13 Participants n=5 Participants	12 Participants n=7 Participants	25 Participants n=5 Participants
Age, Customized Ages 70-79 years	18 Participants n=5 Participants	17 Participants n=7 Participants	35 Participants n=5 Participants
Age, Customized Ages 80-90 years	13 Participants n=5 Participants	8 Participants n=7 Participants	21 Participants n=5 Participants
Sex: Female, Male Female	20 Participants n=5 Participants	13 Participants n=7 Participants	33 Participants n=5 Participants
Sex: Female, Male Male	30 Participants n=5 Participants	33 Participants n=7 Participants	63 Participants n=5 Participants
Race/Ethnicity, Customized White	31 Participants n=5 Participants	30 Participants n=7 Participants	61 Participants n=5 Participants
Race/Ethnicity, Customized Black	18 Participants n=5 Participants	16 Participants n=7 Participants	34 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	50 number of participants n=5 Participants	46 number of participants n=7 Participants	96 number of participants n=5 Participants
Baseline performance status 0	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Baseline performance status 1	16 Participants n=5 Participants	13 Participants n=7 Participants	29 Participants n=5 Participants
Baseline performance status 2	28 Participants n=5 Participants	29 Participants n=7 Participants	57 Participants n=5 Participants
Baseline performance status 3	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants

PRIMARY outcome

Timeframe: 1 year

Outcome measures

Outcome measures
Measure	Radiation Therapy n=50 Participants Arm A:Image-Guided Radiation Therapy (IGRT), 60 Gy in 15 fractions in 3 weeks Radiation Therapy: Image-Guided Radiation Therapy (IGRT)60 Gy in 15 fractions in 3 weeks	Conventional Radiation n=46 Participants Arm B: Conventional radiation 60-66 Gy in 30-33 fractions in 6-7 weeks Conventional radiation: Conventional radiation 60-66 Gy in 30-33 fractions in 6-7 weeks
Overall Survival of Standard Radiation (CFRT) Versus Accelerated, Hypofractionated, Image-guided Conformal Radiotherapy (IGRT) in Treatment of Stage II-III NSCLC in Patients With Poor Performance Status at 1 Year.	37.7 percentage of participants Interval 24.2 to 51.0	44.6 percentage of participants Interval 29.9 to 58.3

SECONDARY outcome

Timeframe: 60 months

To compare toxicity of two radiotherapy treatment regimens in patient with stage II-III Non-Small Cell Lung Cancer (NSCLC) and poor performance status. Toxicity will be assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 4.0.

Outcome measures

Outcome measures
Measure	Radiation Therapy n=50 Participants Arm A:Image-Guided Radiation Therapy (IGRT), 60 Gy in 15 fractions in 3 weeks Radiation Therapy: Image-Guided Radiation Therapy (IGRT)60 Gy in 15 fractions in 3 weeks	Conventional Radiation n=46 Participants Arm B: Conventional radiation 60-66 Gy in 30-33 fractions in 6-7 weeks Conventional radiation: Conventional radiation 60-66 Gy in 30-33 fractions in 6-7 weeks
Toxicities of Two Radiotherapy Treatment Regimens in Patients With Stage II-III Non-Small Cell Lung Cancer (NSCLC) and Poor Performance Status	144 events	120 events

SECONDARY outcome

Timeframe: 60 months

The time to disease progression and time to local regression will be estimated using the Kaplan-Meier approach. The stratified log-rank test will be used to test for a statistically significant difference in PFS (progression-free survival) and time to local progression distributions. The Cox proportional hazard regression model will be used to determine hazard ratios and 95% confidence intervals for the treatment difference in progression-free survival and time to local progression. Time to progression will be measured from the date of study enrollment to the date of documented local progression as determined by clinical exam and imaging studies.

Outcome measures

Outcome measures
Measure	Radiation Therapy n=50 Participants Arm A:Image-Guided Radiation Therapy (IGRT), 60 Gy in 15 fractions in 3 weeks Radiation Therapy: Image-Guided Radiation Therapy (IGRT)60 Gy in 15 fractions in 3 weeks	Conventional Radiation n=46 Participants Arm B: Conventional radiation 60-66 Gy in 30-33 fractions in 6-7 weeks Conventional radiation: Conventional radiation 60-66 Gy in 30-33 fractions in 6-7 weeks
Time to Local Progression of Two Radiotherapy Treatment Regimens in Patients With Stage II-III NSCLC and Poor Performance Status	6.4 months Interval 4.1 to 7.8	7.3 months Interval 5.0 to 10.6

SECONDARY outcome

Timeframe: 60 months

Percentage of patients with disease-free survival at 60 months. To compare disease-free survival of two radiotherapy treatment regimens in patients with stage II-III NSCLC and poor performance status. Unlike progression-free survival in the advanced cancer setting, which refers to time from treatment to disease progression (or death) in patients who already have measurable cancer in their bodies, DFS (disease-free survival) refers to time from treatment until the recurrence of disease (or death) after undergoing curative-intent treatment.

Outcome measures

Outcome measures
Measure	Radiation Therapy n=50 Participants Arm A:Image-Guided Radiation Therapy (IGRT), 60 Gy in 15 fractions in 3 weeks Radiation Therapy: Image-Guided Radiation Therapy (IGRT)60 Gy in 15 fractions in 3 weeks	Conventional Radiation n=46 Participants Arm B: Conventional radiation 60-66 Gy in 30-33 fractions in 6-7 weeks Conventional radiation: Conventional radiation 60-66 Gy in 30-33 fractions in 6-7 weeks
Disease-free Survival of Two Radiotherapy Treatment Regimens in Patients With Stage II-III NSCLC and Poor Performance Status.	4 percentage of participants	2 percentage of participants

SECONDARY outcome

Timeframe: 6 months

Population: Data was not collected due to patient compliance.

Patient-reported functional status will be assessed with the lung cancer subscales of the Functional Assessment of Cancer Therapy-Lung (FACT-L). The FACT-L is a 36-item questionnaire that uses 5-point Likert-type response choices (0 = not at all; 1 = a little bit; 2 =somewhat; 3 = quite a bit; 4 = very much).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2 years

Population: Due to patient compliance with questionnaire completion, only 23 patients from Arm A and 29 patients from Arm B were analyzed. Sample size was too small for meaningful cost comparison.

For the primary analysis, we will estimate cost accumulated within 2 years. An inverse-probability weighting method to calculate average costs for each treatment group will be used to analyze.

Outcome measures

Outcome measures
Measure	Radiation Therapy n=23 Participants Arm A:Image-Guided Radiation Therapy (IGRT), 60 Gy in 15 fractions in 3 weeks Radiation Therapy: Image-Guided Radiation Therapy (IGRT)60 Gy in 15 fractions in 3 weeks	Conventional Radiation n=29 Participants Arm B: Conventional radiation 60-66 Gy in 30-33 fractions in 6-7 weeks Conventional radiation: Conventional radiation 60-66 Gy in 30-33 fractions in 6-7 weeks
Cost Effectiveness of Two Radiotherapy Treatment Regimens in Patients With Stage II-III NSCLC and Poor Performance Status.	26,984 Cost of Treatment (in USD) Interval 14714.0 to 39253.0	33,723 Cost of Treatment (in USD) Interval 12188.0 to 55256.0

SECONDARY outcome

Timeframe: 20 months

The quality-adjusted survival time is just an integration of the utility measures over a patient's survival time, or until the time limit similar as the cost calculation, whichever occurs earlier. To estimate quality adjusted survival time, data from EQ-5D (EuroQol- 5 Dimension a descriptive system for health-related quality of life states in adults), each of which has five severity levels that are described by statements appropriate to that dimension) will first be translated into utility measures. These measures are obtained at discrete time points, so they will be interpolated into the time intervals between the visits. Accordingly, we will use the inverse-probability weighted method of Zhao and Tsiatis to carry out the survival time analysis.

Outcome measures

Outcome measures
Measure	Radiation Therapy n=23 Participants Arm A:Image-Guided Radiation Therapy (IGRT), 60 Gy in 15 fractions in 3 weeks Radiation Therapy: Image-Guided Radiation Therapy (IGRT)60 Gy in 15 fractions in 3 weeks	Conventional Radiation n=29 Participants Arm B: Conventional radiation 60-66 Gy in 30-33 fractions in 6-7 weeks Conventional radiation: Conventional radiation 60-66 Gy in 30-33 fractions in 6-7 weeks
Quality Adjusted Life Survival Time of Two Radiotherapy Treatment Regimens in Patients With Stage II-III NSCLC and Poor Performance Status.	100 days Interval 70.0 to 130.0	81 days Interval 48.0 to 115.0

SECONDARY outcome

Timeframe: 20 months

The quality-adjusted survival time is just an integration of the utility measures over a patient's survival time, or until the time limit similar as the cost calculation, whichever occurs earlier. To estimate quality adjusted survival time, data from the VAS (visual analogue scale: the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine') of EQ-5D (EuroQol- 5 Dimension a descriptive system for health-related quality of life states in adults), each of which has five severity levels that are described by statements appropriate to that dimension) will first be translated into utility measures. These measures are obtained at discrete time points, so they will be interpolated into the time intervals between the visits. Accordingly, we will use the inverse-probability weighted method of Zhao and Tsiatis to carry out the survival time analysis.

Outcome measures

Outcome measures
Measure	Radiation Therapy n=23 Participants Arm A:Image-Guided Radiation Therapy (IGRT), 60 Gy in 15 fractions in 3 weeks Radiation Therapy: Image-Guided Radiation Therapy (IGRT)60 Gy in 15 fractions in 3 weeks	Conventional Radiation n=29 Participants Arm B: Conventional radiation 60-66 Gy in 30-33 fractions in 6-7 weeks Conventional radiation: Conventional radiation 60-66 Gy in 30-33 fractions in 6-7 weeks
Quality Adjusted Life Survival Time of Two Radiotherapy Treatment Regimens in Patients With Stage II-III NSCLC and Poor Performance Status.	106 adjusted days of follow up Interval 73.0 to 139.0	83 adjusted days of follow up Interval 45.0 to 122.0

Adverse Events

Radiation Therapy

Serious events: 0 serious events

Other events: 28 other events

Deaths: 32 deaths

Conventional Radiation

Serious events: 0 serious events

Other events: 23 other events

Deaths: 26 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Dr. Puneeth Iyengar

University of Texas Southwestern Medical Center

Phone: 214-645-7603

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Other adverse events
Measure	Radiation Therapy n=50 participants at risk Arm A:Image-Guided Radiation Therapy (IGRT), 60 Gy in 15 fractions in 3 weeks Radiation Therapy: Image-Guided Radiation Therapy (IGRT)60 Gy in 15 fractions in 3 weeks	Conventional Radiation n=46 participants at risk Arm B: Conventional radiation 60-66 Gy in 30-33 fractions in 6-7 weeks Conventional radiation: Conventional radiation 60-66 Gy in 30-33 fractions in 6-7 weeks
Cardiac disorders Pericardial Effusion	0.00% 0/50 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event	2.2% 1/46 • Number of events 1 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event
Cardiac disorders SVC (Superior vena cava) Syndrome	0.00% 0/50 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event	2.2% 1/46 • Number of events 1 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event
Nervous system disorders Fatigue	46.0% 23/50 • Number of events 23 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event	50.0% 23/46 • Number of events 23 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event
Gastrointestinal disorders Anorexia	14.0% 7/50 • Number of events 7 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event	21.7% 10/46 • Number of events 10 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event
Gastrointestinal disorders Dysphagia	24.0% 12/50 • Number of events 12 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event	21.7% 10/46 • Number of events 10 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event
Gastrointestinal disorders Esophagitis	40.0% 20/50 • Number of events 20 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event	34.8% 16/46 • Number of events 16 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event
Gastrointestinal disorders Nausea	2.0% 1/50 • Number of events 1 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event	4.3% 2/46 • Number of events 2 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event
Musculoskeletal and connective tissue disorders Back Pain	2.0% 1/50 • Number of events 1 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event	0.00% 0/46 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event
Musculoskeletal and connective tissue disorders Chest Wall Pain	8.0% 4/50 • Number of events 4 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event	6.5% 3/46 • Number of events 3 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event
Respiratory, thoracic and mediastinal disorders ARDS (Acute respiratory distress syndrome)	2.0% 1/50 • Number of events 1 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event	0.00% 0/46 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event
Respiratory, thoracic and mediastinal disorders Atelectasis	4.0% 2/50 • Number of events 2 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event	2.2% 1/46 • Number of events 1 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event
Respiratory, thoracic and mediastinal disorders Bronchitis	0.00% 0/50 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event	2.2% 1/46 • Number of events 1 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event
Respiratory, thoracic and mediastinal disorders Cough	16.0% 8/50 • Number of events 8 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event	23.9% 11/46 • Number of events 11 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event
Respiratory, thoracic and mediastinal disorders DLCO (Diffusion capacity of carbon monoxide) decline	6.0% 3/50 • Number of events 3 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event	0.00% 0/46 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event
Respiratory, thoracic and mediastinal disorders Dyspnea	56.0% 28/50 • Number of events 28 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event	28.3% 13/46 • Number of events 13 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event
Respiratory, thoracic and mediastinal disorders FEV (forced expiratory volume) decline	4.0% 2/50 • Number of events 2 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event	0.00% 0/46 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event
Respiratory, thoracic and mediastinal disorders Hemoptysis	0.00% 0/50 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event	6.5% 3/46 • Number of events 3 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event
Respiratory, thoracic and mediastinal disorders Pleural effusion	18.0% 9/50 • Number of events 9 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event	10.9% 5/46 • Number of events 5 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event
Respiratory, thoracic and mediastinal disorders Pneumonia	4.0% 2/50 • Number of events 2 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event	8.7% 4/46 • Number of events 4 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event
Respiratory, thoracic and mediastinal disorders Pneumonitis	10.0% 5/50 • Number of events 5 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event	6.5% 3/46 • Number of events 3 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event
Respiratory, thoracic and mediastinal disorders Pulmonary fibrosis	2.0% 1/50 • Number of events 1 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event	0.00% 0/46 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event
Respiratory, thoracic and mediastinal disorders Wheezing	8.0% 4/50 • Number of events 4 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event	2.2% 1/46 • Number of events 1 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event
Skin and subcutaneous tissue disorders Dermatitis	16.0% 8/50 • Number of events 8 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event	13.0% 6/46 • Number of events 6 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event
Skin and subcutaneous tissue disorders Dryness	0.00% 0/50 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event	2.2% 1/46 • Number of events 1 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event
Skin and subcutaneous tissue disorders Hyperpigmentation	2.0% 1/50 • Number of events 1 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event	6.5% 3/46 • Number of events 3 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event
Skin and subcutaneous tissue disorders Pruritis	2.0% 1/50 • Number of events 1 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event	0.00% 0/46 • 60 months Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event