Trial Outcomes & Findings for Radiation Therapy in Treating Patients With Stage I Non-Small Cell Lung Cancer (NCT NCT00960999)

Last Updated: 2020-03-04

Results Overview

Number of patients with ≥ grade 3 AE occurring within 1 year of treatment (TRT) start and reported as DPPRT among this subset of CTCAE v4: pericardial effusion, pericarditis, restrictive cardiomyopathy, dysphagia, esophagitis, esophageal fistula/obstruction/perforation/stenosis/ulcer/hemorrhage, rib fracture, brachial plexopathy, recurrent laryngeal nerve palsy, myelitis, atelectasis, bronchopulmonary/mediastinal/pleural/tracheal hemorrhage, bronchial/pulmonary/bronchopleural/tracheal fistula, hypoxia, bronchial/tracheal obstruction, pleural effusion, pneumonitis, pulmonary fibrosis, skin ulceration (thorax only), FEV1 (Forced Expiratory Volume) or FVC (forced vital capacity) decline, or grade 5 related to TRT. Each arm is considered independently. For each arm, \>=5 of 38 analyzable subjects experiencing a grade ≥ 3 AE during the 1st year following TRT start would determine the respective TRT excessively toxic. For each arm this design provides 88% power with a 0.10 type I error rate.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

94 participants

Primary outcome timeframe

From start of treatment to 1 year

Results posted on

2020-03-04

Participant Flow

Participant milestones

Participant milestones
Measure	Single-fraction SBRT (34 Gy) Single-fraction stereotactic body radiation therapy (SBRT) of 34 Gy	Multiple-fraction SBRT (48 Gy) Multiple-fraction stereotactic body radiation therapy (SBRT) given in four daily 12 Gy fractions for a total dose of 48 Gy
Overall Study STARTED	47	47
Overall Study Eligible	39	45
Overall Study Started Protocol Treatment	39	45
Overall Study Primary Endpoint Population	38	38
Overall Study Peak SUV at 8 Weeks	3	11
Overall Study Peak SUV at 1 Year	4	7
Overall Study Normalized SUV at 8 Weeks	3	9
Overall Study Normalized SUV at 1 Year	4	7
Overall Study FEV1 by Best Response	26	33
Overall Study DLCO by Best Response	23	28
Overall Study COMPLETED	39	45
Overall Study NOT COMPLETED	8	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Single-fraction SBRT (34 Gy) Single-fraction stereotactic body radiation therapy (SBRT) of 34 Gy	Multiple-fraction SBRT (48 Gy) Multiple-fraction stereotactic body radiation therapy (SBRT) given in four daily 12 Gy fractions for a total dose of 48 Gy
Overall Study Withdrawal by Subject	1	0
Overall Study Protocol Violation	5	2
Overall Study RT dose constraints not met	2	0

Baseline Characteristics

Radiation Therapy in Treating Patients With Stage I Non-Small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Single-fraction SBRT (34 Gy) n=39 Participants Single-fraction stereotactic body radiation therapy (SBRT) of 34 Gy	Multiple-fraction SBRT (48 Gy) n=45 Participants Multiple-fraction stereotactic body radiation therapy (SBRT) given in four daily 12 Gy fractions for a total dose of 48 Gy	Total n=84 Participants Total of all reporting groups
Age, Continuous	75 years n=5 Participants	75 years n=7 Participants	75 years n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants	23 Participants n=7 Participants	46 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	22 Participants n=7 Participants	38 Participants n=5 Participants

PRIMARY outcome

Timeframe: From start of treatment to 1 year

Population: First 38 eligible patients per arm who started treatment

Outcome measures

Outcome measures
Measure	Single-fraction SBRT (34 Gy) n=38 Participants Single-fraction stereotactic body radiation therapy (SBRT) of 34 Gy	Multiple-fraction SBRT (48 Gy) n=38 Participants Multiple-fraction stereotactic body radiation therapy (SBRT) given in four daily 12 Gy fractions for a total dose of 48 Gy
Counts of ≥ Grade 3 Adverse Events (AE) Graded by CTCAE v4 (Common Terminology Criteria for Adverse Events) That Are Definitely, Probably, or Possibly Related to Treatment (DPPRT)	3 participants	6 participants

SECONDARY outcome

Timeframe: From start of treatment to 1 year

Population: Eligible participants

Primary tumor control is defined as the lack of primary tumor failure. Primary tumor failure is defined as the development of in-field or marginal failure. Primary tumor control time is defined as time from randomization to the the date of primary tumor failure, last known follow-up (censored), or death without failure (competing risk). Primary tumor control rates are estimated using the cumulative incidence method.

Outcome measures

Outcome measures
Measure	Single-fraction SBRT (34 Gy) n=39 Participants Single-fraction stereotactic body radiation therapy (SBRT) of 34 Gy	Multiple-fraction SBRT (48 Gy) n=45 Participants Multiple-fraction stereotactic body radiation therapy (SBRT) given in four daily 12 Gy fractions for a total dose of 48 Gy
1-year Primary Tumor Control Rate	97.1 percentage of participants Interval 85.1 to 99.9	97.6 percentage of participants Interval 87.1 to 99.9

SECONDARY outcome

Timeframe: From start of treatment to 1 year

Population: Eligible participants

Overall survival time is defined as time from registration/randomization to the date of death from any cause or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Single-fraction SBRT (34 Gy) n=39 Participants Single-fraction stereotactic body radiation therapy (SBRT) of 34 Gy	Multiple-fraction SBRT (48 Gy) n=45 Participants Multiple-fraction stereotactic body radiation therapy (SBRT) given in four daily 12 Gy fractions for a total dose of 48 Gy
1-year Overall Survival Rate	85.4 percentage of participants Interval 70.3 to 93.1	91.1 percentage of participants Interval 78.0 to 96.6

SECONDARY outcome

Timeframe: From start of treatment to 1 year

Population: Eligible participants

Disease-free survival is defined as being alive without experiencing in-field, marginal, involved lobe, regional or metastatic failure, development of a second primary, or death due to any cause. Disease-free survival time is defined as time from randomization to the the date of first failure or last known follow-up (censored). Disease-free survival rates are estimated using the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Single-fraction SBRT (34 Gy) n=39 Participants Single-fraction stereotactic body radiation therapy (SBRT) of 34 Gy	Multiple-fraction SBRT (48 Gy) n=45 Participants Multiple-fraction stereotactic body radiation therapy (SBRT) given in four daily 12 Gy fractions for a total dose of 48 Gy
1-year Disease-free Survival Rate	78.0 percentage of participants Interval 62.1 to 87.9	84.4 percentage of participants Interval 70.1 to 92.3

SECONDARY outcome

Timeframe: Baseline and 12 weeks post-radiotherapy

Population: eligible patients with PET SUV data at at baseline and 12 weeks

Standardized uptake value (SUV) describes the level of biologic activity in a particular spot compared to activity elsewhere in the body. An SUV reading of 1 is considered normal cellular activity, with higher values indicating increased activity. Peak SUV is an average SUV computed within a fixed-size volume of interest (VOI), most often containing (and not necessarily centered on) the hottest pixel value. Peak SUV was measured from whole-body FDG-PET (fluorodeoxyglucose - positron emission tomography) scans that were required at baseline and requested (not required) at 12 weeks and 12 months post-radiotherapy. Change from baseline is calculated by subtracting the follow-up value from the baseline value. A positive change from baseline indicates decreased SUV.

Outcome measures

Outcome measures
Measure	Single-fraction SBRT (34 Gy) n=3 Participants Single-fraction stereotactic body radiation therapy (SBRT) of 34 Gy	Multiple-fraction SBRT (48 Gy) n=11 Participants Multiple-fraction stereotactic body radiation therapy (SBRT) given in four daily 12 Gy fractions for a total dose of 48 Gy
Change in Peak Standardized Uptake Value (SUV) at 12 Weeks Post-radiotherapy	2.8 SUV Interval -1.3 to 5.0	1.4 SUV Interval -3.4 to 10.5

SECONDARY outcome

Timeframe: Baseline and one year

Population: eligible patients with PET SUV data at at baseline and one year

Standardized uptake value (SUV) describes the level of biologic activity in a particular spot compared to activity elsewhere in the body. An SUV reading of 1 is considered normal cellular activity, with higher values indicating increased activity. Peak SUV is an average SUV computed within a fixed-size volume of interest (VOI), most often containing (and not necessarily centered on) the hottest pixel value. Peak SUV was measured from whole-body FDG-PET scans that were required at baseline and requested (not required) at 12 weeks and 12 months post-radiotherapy. Change from baseline is calculated by subtracting the follow-up value from the baseline value. A positive change from baseline indicates decreased SUV. SUV does not have a unit.

Outcome measures

Outcome measures
Measure	Single-fraction SBRT (34 Gy) n=4 Participants Single-fraction stereotactic body radiation therapy (SBRT) of 34 Gy	Multiple-fraction SBRT (48 Gy) n=7 Participants Multiple-fraction stereotactic body radiation therapy (SBRT) given in four daily 12 Gy fractions for a total dose of 48 Gy
Change in Peak Standardized Uptake Value (SUV) at One Year Post-radiotherapy	-0.8 SUV Interval -5.2 to 2.4	3.6 SUV Interval -1.2 to 12.9

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: eligible patients with normalized SUV at baseline and 12 weeks

Standardized uptake value (SUV) describes the level of biologic activity in a particular spot compared to activity elsewhere in the body. An SUV reading of 1 is considered normal cellular activity, with higher values indicating increased activity. SUV was measured from whole-body FDG-PET scans that were required at baseline and requested (not required) at 12 weeks and 12 months post-radiotherapy. Normalized SUV = peak SUV of regions of interest / mean SUV of the aortic arch. Change from baseline is calculated by subtracting the follow-up value from the baseline value. A positive change from baseline indicates decreased SUV. SUV does not have a unit.

Outcome measures

Outcome measures
Measure	Single-fraction SBRT (34 Gy) n=3 Participants Single-fraction stereotactic body radiation therapy (SBRT) of 34 Gy	Multiple-fraction SBRT (48 Gy) n=9 Participants Multiple-fraction stereotactic body radiation therapy (SBRT) given in four daily 12 Gy fractions for a total dose of 48 Gy
Change in Normalized Standardized Uptake Value (SUV) at 12 Weeks	3.9 SUV Interval 1.1 to 4.2	1.4 SUV Interval -2.5 to 7.2

SECONDARY outcome

Timeframe: Baseline and one year

Population: eligible patients with normalized SUV at baseline and one year

Standardized uptake value (SUV) describes the level of biologic activity in a particular spot compared to activity elsewhere in the body. An SUV reading of 1 is considered normal cellular activity, with higher values indicating increased activity. SUV was measured from whole-body FDG-PET scans that were required at baseline and requested (not required) at 12 weeks and 12 months post-radiotherapy. Normalized SUV = peak SUV of regions of interest / mean SUV of the aortic arch. Change from baseline is calculated by subtracting the follow-up value from the baseline value. A positive change from baseline indicates decreased SUV. SUV does not have a unit.

Outcome measures

Outcome measures
Measure	Single-fraction SBRT (34 Gy) n=4 Participants Single-fraction stereotactic body radiation therapy (SBRT) of 34 Gy	Multiple-fraction SBRT (48 Gy) n=7 Participants Multiple-fraction stereotactic body radiation therapy (SBRT) given in four daily 12 Gy fractions for a total dose of 48 Gy
Change in Normalized Standardized Uptake Value (SUV) at One Year	1.0 SUV Interval -0.7 to 4.1	3.9 SUV Interval -1.6 to 9.4

SECONDARY outcome

Timeframe: From start of treatment to 6 months post-radiotherapy

Population: Eligible patients with FEV1 at baseline and 6 months, and with best tumor response of complete response, partial response, or stable disease

Forced expiratory volume (FEV1), a measure of pulmonary function, was reported as percentage of the value that would be expected for the normal general population of the same height, age, and sex. Change from baseline is calculated by subtracting the follow-up value from the baseline value. A positive change from baseline indicates decreased FEV1. Best observed tumor response was evaluated using the Revised Response Evaluation Criteria in Solid Tumors (RECIST) criteria v1.1 (http://ctep.cancer.gov/protocolDevelopment/docs/recist\_guideline.pdf).

Outcome measures

Outcome measures
Measure	Single-fraction SBRT (34 Gy) n=26 Participants Single-fraction stereotactic body radiation therapy (SBRT) of 34 Gy	Multiple-fraction SBRT (48 Gy) n=33 Participants Multiple-fraction stereotactic body radiation therapy (SBRT) given in four daily 12 Gy fractions for a total dose of 48 Gy
Change in Percentage of Expected Forced Expiratory Volume in 1 Second (FEV1) by Best Observed Tumor Response at 6 Months Post-radiotherapy [Forced Expiratory Volume in 1 Second (FEV1)] Complete Response	-2.0 percentage of predicted value Standard Deviation 10.8	-12.4 percentage of predicted value Standard Deviation 28.0
Change in Percentage of Expected Forced Expiratory Volume in 1 Second (FEV1) by Best Observed Tumor Response at 6 Months Post-radiotherapy [Forced Expiratory Volume in 1 Second (FEV1)] Partial Response	-0.7 percentage of predicted value Standard Deviation 7.9	5.9 percentage of predicted value Standard Deviation 9.0
Change in Percentage of Expected Forced Expiratory Volume in 1 Second (FEV1) by Best Observed Tumor Response at 6 Months Post-radiotherapy [Forced Expiratory Volume in 1 Second (FEV1)] Stable Disease	-0.5 percentage of predicted value Standard Deviation 7.6	-6.1 percentage of predicted value Standard Deviation 11.0

SECONDARY outcome

Timeframe: From start of treatment to 6 months post-radiotherapy

Population: Eligible patients with DLCO at baseline and 6 months, and with best tumor response of complete response, partial response, or stable disease

Carbon monoxide diffusing capacity (DLCO), a measure of pulmonary function, was reported as percentage of the value that would be expected for the normal general population of the same height, age, and sex. Change from baseline is calculated by subtracting the follow-up value from the baseline value. A positive change from baseline indicates decreased DLCO. Best observed tumor response was evaluated using the Revised Response Evaluation Criteria in Solid Tumors (RECIST) criteria v1.1 (http://ctep.cancer.gov/protocolDevelopment/docs/recist\_guideline.pdf).

Outcome measures

Outcome measures
Measure	Single-fraction SBRT (34 Gy) n=23 Participants Single-fraction stereotactic body radiation therapy (SBRT) of 34 Gy	Multiple-fraction SBRT (48 Gy) n=28 Participants Multiple-fraction stereotactic body radiation therapy (SBRT) given in four daily 12 Gy fractions for a total dose of 48 Gy
Change in Percentage of Expected Carbon Monoxide Diffusing Capacity (DLCO) by Best Observed Tumor Response at 6 Months Post-radiotherapy Complete Response	0.1 percentage of predicted value Standard Deviation 23.1	-2.7 percentage of predicted value Standard Deviation 20.5
Change in Percentage of Expected Carbon Monoxide Diffusing Capacity (DLCO) by Best Observed Tumor Response at 6 Months Post-radiotherapy Partial Response	4.1 percentage of predicted value Standard Deviation 9.8	2.6 percentage of predicted value Standard Deviation 9.1
Change in Percentage of Expected Carbon Monoxide Diffusing Capacity (DLCO) by Best Observed Tumor Response at 6 Months Post-radiotherapy Stable Disease	12.7 percentage of predicted value Standard Deviation 10.7	-28.0 percentage of predicted value Standard Deviation 30.6

SECONDARY outcome

Timeframe: From start of treatment to 1 year

Population: The protocol did not provide sufficient detail to meet National Cancer Institute requirements for release of specimens from the NRG tissue bank for the protocol-specified analysis, therefore no assays were performed and no data were collected for this outcome measure. Specimen use will require federal approval and funding separate from this trial.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From start of treatment to 1 year

Outcome measures

Outcome data not reported

Adverse Events

Single-fraction SBRT (34 Gy)

Serious events: 3 serious events

Other events: 27 other events

Deaths: 0 deaths

Multiple-fraction SBRT (48 Gy)

Serious events: 3 serious events

Other events: 30 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Single-fraction SBRT (34 Gy) n=39 participants at risk Single-fraction stereotactic body radiation therapy (SBRT) of 34 Gy	Multiple-fraction SBRT (48 Gy) n=45 participants at risk Multiple-fraction stereotactic body radiation therapy (SBRT) given in four daily 12 Gy fractions for a total dose of 48 Gy
Cardiac disorders Heart failure	2.6% 1/39 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/45 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.
General disorders Death NOS	2.6% 1/39 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/45 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.
Respiratory, thoracic and mediastinal disorders Adult respiratory distress syndrome	2.6% 1/39 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/45 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/39 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.	2.2% 1/45 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/39 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.	2.2% 1/45 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/39 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.	2.2% 1/45 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.

Other adverse events

Additional Information

Wendy Seiferheld

NRG Oncology

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee PI's are required to abide by the sponsor's publication guidelines which require review by coauthors and subsequent review and approval by the sponsor.
Publication restrictions are in place

Restriction type: OTHER

Measure	Single-fraction SBRT (34 Gy) n=39 participants at risk Single-fraction stereotactic body radiation therapy (SBRT) of 34 Gy	Multiple-fraction SBRT (48 Gy) n=45 participants at risk Multiple-fraction stereotactic body radiation therapy (SBRT) given in four daily 12 Gy fractions for a total dose of 48 Gy
Cardiac disorders Pericardial effusion	5.1% 2/39 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.	2.2% 1/45 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.
Gastrointestinal disorders Dysphagia	2.6% 1/39 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.	6.7% 3/45 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.
Gastrointestinal disorders Nausea	0.00% 0/39 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.	6.7% 3/45 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.
Gastrointestinal disorders Vomiting	0.00% 0/39 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.	8.9% 4/45 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.
General disorders Fatigue	17.9% 7/39 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.	22.2% 10/45 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.
Infections and infestations Lung infection	5.1% 2/39 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.	2.2% 1/45 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.
Injury, poisoning and procedural complications Fracture	17.9% 7/39 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.	4.4% 2/45 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.
Investigations Carbon monoxide diffusing capacity decreased	12.8% 5/39 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.	2.2% 1/45 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.
Investigations Forced expiratory volume decreased	7.7% 3/39 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.	4.4% 2/45 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.
Investigations Vital capacity abnormal	5.1% 2/39 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.	2.2% 1/45 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.
Investigations Weight loss	0.00% 0/39 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.	6.7% 3/45 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.
Metabolism and nutrition disorders Anorexia	2.6% 1/39 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.	6.7% 3/45 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.
Musculoskeletal and connective tissue disorders Chest wall pain	20.5% 8/39 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.	4.4% 2/45 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other	5.1% 2/39 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/45 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.
Respiratory, thoracic and mediastinal disorders Atelectasis	17.9% 7/39 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.	13.3% 6/45 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.
Respiratory, thoracic and mediastinal disorders Cough	10.3% 4/39 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.	15.6% 7/45 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.
Respiratory, thoracic and mediastinal disorders Dyspnea	17.9% 7/39 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.	11.1% 5/45 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.
Respiratory, thoracic and mediastinal disorders Hypoxia	2.6% 1/39 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.	13.3% 6/45 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.
Respiratory, thoracic and mediastinal disorders Pleural effusion	25.6% 10/39 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.	26.7% 12/45 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.
Respiratory, thoracic and mediastinal disorders Pneumonitis	15.4% 6/39 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.	17.8% 8/45 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.
Respiratory, thoracic and mediastinal disorders Productive cough	5.1% 2/39 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.	4.4% 2/45 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.
Respiratory, thoracic and mediastinal disorders Pulmonary fibrosis	23.1% 9/39 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.	15.6% 7/45 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.
Respiratory, thoracic and mediastinal disorders Wheezing	5.1% 2/39 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/45 Eligible participants who started protocol treatment. Participants experiencing more than one of a given adverse event are counted only once for that adverse event.