A Randomized Phase 2 Study of Atezolizumab (an Engineered Anti-PDL1 Antibody) Compared With Docetaxel in Participants With Locally Advanced or Metastatic Non-Small Cell Lung Cancer Who Have Failed Platinum Therapy - "POPLAR"

• ClinicalTrials.gov Identifier: NCT01903993
• Recruitment Status: Completed
• First Posted: July 19, 2013
• Results First Posted: May 23, 2017
• Last Update Posted: October 2, 2019
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non-Small Cell Lung Cancer
• Interventions: Drug: Docetaxel; Drug: Atezolizumab
• Enrollment: 287

Participant Flow

Recruitment Details
Pre-assignment Details	A total of 527 participants were screened, of whom 287 participants were randomized. 143 participants to the docetaxel arm and 144 participants to the atezolizumab arm. Overall, 10 participants (8 in the docetaxel arm and 2 in the atezolizumab arm) did not receive any study treatment.

Arm/Group Title	Docetaxel	Atezolizumab
Arm/Group Description	Participants received docetaxel 75 milligram per squared meters (mg/m^2) administered intravenously on Day 1 of each 21 day cycle until disease progression or unacceptable toxicity or death.	Participants were administered atezolizumab intravenously on Day 1 of each 21 day cycle at a fixed dose of 1200 mg. Atezolizumab treatment were to continued as long as participants were experiencing clinical benefit as assessed by the investigator.
Period Title: Overall Study
Started	143	144
Received Treatment [1]	135	142
Completed [2]	0	0
Not Completed	143	144
Reason Not Completed
Death	118	121
Withdrawal by Subject	15	4
Lost to Follow-up	2	3
Study Terminated by Sponsor	8	14
Terminated by Sponsor After 31 Aug 2018	0	2
[1] Two patients in the docetaxel arm crossed over to receive atezolizumab treatment.; [2] Study terminated by Sponsor participants either discontinued or enrolled in extension study

Baseline Characteristics

Arm/Group Title		Docetaxel	Atezolizumab	Total
Arm/Group Description		Participants received docetaxel 75 milligram per squared meters (mg/m^2) administered intravenously on Day 1 of each 21 day cycle until disease progression or unacceptable toxicity or death.	Participants were administered atezolizumab intravenously on Day 1 of each 21 day cycle at a fixed dose of 1200 mg. Atezolizumab treatment were to continued as long as participants were experiencing clinical benefit as assessed by the investigator.	Total of all reporting groups
Overall Number of Baseline Participants		143	144	287
Baseline Analysis Population Description		Intent to treat (ITT) population for efficacy analyses included all randomized participants, regardless of whether they received any study drug. In the efficacy analyses, the ITT population, participants were grouped according to the treatment arm to which they were assigned.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	143 participants	144 participants	287 participants
		61.8 (9.4)	61.5 (9.2)	61.6 (9.3)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	143 participants	144 participants	287 participants
	Female	67 46.9%	51 35.4%	118 41.1%
	Male	76 53.1%	93 64.6%	169 58.9%

Outcome Measures

1. Primary Outcome

Title	Overall Survival (OS)
Description	Overall Survival (OS) was defined as the time from the date of randomization to the date of death due to any cause. Data for participants who were not reported as dead at the time of analysis was censored at the date when they were last known to be alive.
Time Frame	From the time of randomization to the date of death due to any cause or up to data cut off date: 01 Dec 2015 (up to 28 months)

Outcome Measure Data

Analysis Population Description

ITT population for efficacy analyses included all randomized participants, regardless of whether they received any study drug. In the efficacy analyses, the ITT population, participants were grouped according to the treatment arm to which they were assigned.

Arm/Group Title	Docetaxel	Atezolizumab
Arm/Group Description:	Participants received docetaxel 75 milligram per squared meters (mg/m^2) administered intravenously on Day 1 of each 21 day cycle until disease progression or unacceptable toxicity or death.	Participants were administered atezolizumab intravenously on Day 1 of each 21 day cycle at a fixed dose of 1200 mg. Atezolizumab treatment were to continued as long as participants were experiencing clinical benefit as assessed by the investigator.
Overall Number of Participants Analyzed	143	144
Median (95% Confidence Interval); Unit of Measure: months
	9.7; (8.6 to 12.0)	12.6; (9.7 to 16.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Docetaxel, Atezolizumab
	Comments	Hazard ratios (HR) were estimated by a Cox regression model.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	= 0.0106
	Comments	[Not Specified]
	Method	Log rank (Stratified)
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.69
	Confidence Interval	(2-Sided) 95%; 0.52 to 0.92
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Objective Response Rate (ORR)
Description	ORR was defined as the percentage of participants with confirmed objective tumor response, complete response (CR) or partial response (PR), as determined by investigator using RECIST v1.1 criteria. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Time Frame	Baseline until date of death due to any cause or up to data cut off date: 01 Dec 2015 (up to 28 months)

Outcome Measure Data

Analysis Population Description

ITT population for efficacy analyses included all randomized participants, regardless of whether they received any study drug. In the efficacy analyses, the ITT population, participants were grouped according to the treatment arm to which they were assigned.

Arm/Group Title	Docetaxel	Atezolizumab
Arm/Group Description:	Participants received docetaxel 75 milligram per squared meters (mg/m^2) administered intravenously on Day 1 of each 21 day cycle until disease progression or unacceptable toxicity or death.	Participants were administered atezolizumab intravenously on Day 1 of each 21 day cycle at a fixed dose of 1200 mg. Atezolizumab treatment were to continued as long as participants were experiencing clinical benefit as assessed by the investigator.
Overall Number of Participants Analyzed	143	144
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	14.7; (9.33 to 21.57)	15.3; (9.83 to 22.21)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Docetaxel, Atezolizumab
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	= 0.8884
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	0.59
	Confidence Interval	(2-Sided) 95%; -7.67 to 8.85
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Progression-Free Survival (PFS)
Description	PFS was defined as the time (in months) between the date of randomization and the date of first documented disease progression or death, whichever occurs first. Disease progression was determined based on investigator assessment using response evaluation criteria In solid tumors (RECIST) v1.1. Progressive disease (PD): at least a 20% increase in the sum of diameters of target lesions including baseline In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.
Time Frame	From the time of randomization to the date of death due to any cause or up to data cut off date: 01 Dec 2015 (up to 28 months)

Outcome Measure Data

Analysis Population Description

ITT population for efficacy analyses included all randomized participants, regardless of whether they received any study drug. In the efficacy analyses, the ITT population, participants were grouped according to the treatment arm to which they were assigned.

Arm/Group Title	Docetaxel	Atezolizumab
Arm/Group Description:	Participants received docetaxel 75 milligram per squared meters (mg/m^2) administered intravenously on Day 1 of each 21 day cycle until disease progression or unacceptable toxicity or death.	Participants were administered atezolizumab intravenously on Day 1 of each 21 day cycle at a fixed dose of 1200 mg. Atezolizumab treatment were to continued as long as participants were experiencing clinical benefit as assessed by the investigator.
Overall Number of Participants Analyzed	143	144
Median (95% Confidence Interval); Unit of Measure: months
	3.4; (2.8 to 4.1)	2.7; (2.0 to 4.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Docetaxel, Atezolizumab
	Comments	HR were estimated by a Cox regression model. The two treatment comparison was based on a stratified log-rank test.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	=0.5563
	Comments	[Not Specified]
	Method	Log rank (Stratified)
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.92
	Confidence Interval	(2-Sided) 95%; 0.71 to 1.20
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Duration of Response (DOR)
Description	DOR was defined as the duration from the first tumor assessment that supports the participant's objective response (CR or PR, whichever is first recorded) to disease progression or death due to any cause, whichever occurs first.
Time Frame	From the time of randomization to the date of death due to any cause or up to data cut off date: 01 Dec 2015 (up to 28 months)

Outcome Measure Data

Analysis Population Description

ITT population for efficacy analyses included all randomized participants, regardless of whether they received any study drug. Here, number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.

Arm/Group Title	Docetaxel	Atezolizumab
Arm/Group Description:	Participants received docetaxel 75 milligram per squared meters (mg/m^2) administered intravenously on Day 1 of each 21 day cycle until disease progression or unacceptable toxicity or death.	Participants were administered atezolizumab intravenously on Day 1 of each 21 day cycle at a fixed dose of 1200 mg. Atezolizumab treatment were to continued as long as participants were experiencing clinical benefit as assessed by the investigator.
Overall Number of Participants Analyzed	21	21
Median (95% Confidence Interval); Unit of Measure: months
	7.2; (5.6 to 12.5)	18.6 [1]; (11.6 to NA)

[1]

Upper limit of confidence interval (CI) was not achieved due to low number of participants with event.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Docetaxel, Atezolizumab
	Comments	HR were estimated by a unstratified Cox regression model.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	= 0.0028
	Comments	[Not Specified]
	Method	Log rank (unstratified)
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.32
	Confidence Interval	(2-Sided) 95%; 0.15 to 0.70
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	ORR (Modified RECIST)
Description	ORR was defined as the percentage of participants with confirmed objective tumor response, CR or PR, as determined by investigator using modified RECIST criteria. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to l< 10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Time Frame	From the time of randomization to the date of death due to any cause or up to data cut off date: 08 May 2015 (up to 21 months)

Outcome Measure Data

Analysis Population Description

ITT population for efficacy analyses included all randomized participants, regardless of whether they received any study drug. In the efficacy analyses, the ITT population, participants were grouped according to the treatment arm to which they were assigned. The data was planned to be reported for Atezolizumab arm only

Arm/Group Title	Atezolizumab
Arm/Group Description:	Participants were administered atezolizumab intravenously on Day 1 of each 21 day cycle at a fixed dose of 1200 mg. Atezolizumab treatment were to continued as long as participants were experiencing clinical benefit as assessed by the investigator.
Overall Number of Participants Analyzed	144
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	16.7; (10.98 to 23.78)

6. Secondary Outcome

Title	PFS (Modified RECIST)
Description	PFS was defined as the time (in months) between the date of randomization and the date of first documented disease progression or death, whichever occurs first. Disease progression was determined based on investigator assessment using modified RECIST criteria. PD: at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.
Time Frame	From the time of randomization to the date of death due to any cause or up to data cut off date: 08 May 2015 (up to 21 months)

Outcome Measure Data

Analysis Population Description

ITT population for efficacy analyses included all randomized participants, regardless of whether they received any study drug. In the efficacy analyses, the ITT population, participants were grouped according to the treatment arm to which they were assigned. The data was planned to be reported for Atezolizumab arm only

Arm/Group Title	Atezolizumab
Arm/Group Description:	Participants were administered atezolizumab intravenously on Day 1 of each 21 day cycle at a fixed dose of 1200 mg. Atezolizumab treatment were to continued as long as participants were experiencing clinical benefit as assessed by the investigator.
Overall Number of Participants Analyzed	144
Median (95% Confidence Interval); Unit of Measure: months
	4.2; (3.9 to 6.9)

7. Secondary Outcome

Title	DOR (Modified RECIST)
Description	DOR was defined as the duration from the first tumor assessment that supports the participant's objective response (CR or PR, whichever is first recorded) to disease progression or death due to any cause, whichever occurs first.
Time Frame	From the time of randomization to the date of death due to any cause or up to data cut off date: 08 May 2015 (up to 21 months)

Outcome Measure Data

Analysis Population Description

ITT population for efficacy analyses included all randomized participants, regardless of whether they received any study drug. Here, number of participants analyzed signifies the number of participants who were evaluable for this outcome measure. The data was planned to be reported for Atezolizumab arm only.

Arm/Group Title	Atezolizumab
Arm/Group Description:	Participants were administered atezolizumab intravenously on Day 1 of each 21 day cycle at a fixed dose of 1200 mg. Atezolizumab treatment were to continued as long as participants were experiencing clinical benefit as assessed by the investigator.
Overall Number of Participants Analyzed	24
Median (95% Confidence Interval); Unit of Measure: months
	14.9 [1]; (11.6 to NA)

[1]

Upper limit of CI was not achieved due to low number of participants with event.

Adverse Events

Time Frame	From the first study drug to the data cutoff date: 31 August 2018
Adverse Event Reporting Description	Treatment-emergent adverse events are reported here and they include all adverse events that occurred on or after first dose of study drug until 30 days after last administration of study drug or initiation of another non-protocol anti-cancer therapy after the last administration of study drug, or clinical data cutoff date, whichever occurs first. Adverse Events reporting is for the Safety Evaluable Population, defined as patients who received any amount of any component of study treatment.
Arm/Group Title	Docetaxel		Atezolizumab
Arm/Group Description	Participants received docetaxel 75 milligram per squared meters (mg/m^2) administered intravenously on Day 1 of each 21 day cycle until disease progression or unacceptable toxicity or death.		Participants were administered atezolizumab intravenously on Day 1 of each 21 day cycle at a fixed dose of 1200 mg. Atezolizumab treatment were to continued as long as participants were experiencing clinical benefit as assessed by the investigator.
All-Cause Mortality
	Docetaxel		Atezolizumab
	Affected / at Risk (%)		Affected / at Risk (%)
Total	118/143 (82.52%)		121/144 (84.03%)
Serious Adverse Events
	Docetaxel		Atezolizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	46/135 (34.07%)		53/142 (37.32%)
Blood and lymphatic system disorders
Anaemia † 1	1/135 (0.74%)	3	0/142 (0.00%)	0
Febrile neutropenia † 1	7/135 (5.19%)	7	0/142 (0.00%)	0
Lymphadenopathy † 1	0/135 (0.00%)	0	1/142 (0.70%)	1
Neutropenia † 1	2/135 (1.48%)	3	0/142 (0.00%)	0
Cardiac disorders
Acute myocardial infarction † 1	1/135 (0.74%)	1	0/142 (0.00%)	0
Atrial fibrillation † 1	1/135 (0.74%)	1	0/142 (0.00%)	0
Cardiac failure † 1	0/135 (0.00%)	0	1/142 (0.70%)	2
Cardiac tamponade † 1	0/135 (0.00%)	0	2/142 (1.41%)	2
Pericardial effusion † 1	1/135 (0.74%)	1	0/142 (0.00%)	0
Sinus tachycardia † 1	1/135 (0.74%)	1	0/142 (0.00%)	0
Myocarditis † 1	0/135 (0.00%)	0	1/142 (0.70%)	1
Gastrointestinal disorders
Abdominal pain † 1	1/135 (0.74%)	1	0/142 (0.00%)	0
Colitis † 1	0/135 (0.00%)	0	1/142 (0.70%)	1
Constipation † 1	1/135 (0.74%)	1	0/142 (0.00%)	0
Diarrhoea † 1	1/135 (0.74%)	1	1/142 (0.70%)	1
Dysphagia † 1	0/135 (0.00%)	0	2/142 (1.41%)	2
Haemorrhoids thrombosed † 1	0/135 (0.00%)	0	1/142 (0.70%)	1
Large intestine perforation † 1	0/135 (0.00%)	0	1/142 (0.70%)	1
Nausea † 1	0/135 (0.00%)	0	1/142 (0.70%)	1
Small intestinal obstruction † 1	0/135 (0.00%)	0	1/142 (0.70%)	1
Upper gastrointestinal haemorrhage † 1	1/135 (0.74%)	1	0/142 (0.00%)	0
General disorders
Asthenia † 1	1/135 (0.74%)	1	0/142 (0.00%)	0
Death † 1	2/135 (1.48%)	2	1/142 (0.70%)	1
Fatigue † 1	1/135 (0.74%)	1	0/142 (0.00%)	0
Influenza like illness † 1	0/135 (0.00%)	0	1/142 (0.70%)	1
Oedema peripheral † 1	0/135 (0.00%)	0	1/142 (0.70%)	1
Pain † 1	0/135 (0.00%)	0	1/142 (0.70%)	1
Pyrexia † 1	1/135 (0.74%)	1	3/142 (2.11%)	3
Ulcer haemorrhage † 1	0/135 (0.00%)	0	1/142 (0.70%)	2
Immune system disorders
Contrast Media Allergy † 1	0/135 (0.00%)	0	1/142 (0.70%)	1
Drug Hypersensitivity † 1	0/135 (0.00%)	0	1/142 (0.70%)	1
Infections and infestations
Bronchitis † 1	0/135 (0.00%)	0	1/142 (0.70%)	1
Cellulitis † 1	0/135 (0.00%)	0	1/142 (0.70%)	1
H1N1 influenza † 1	0/135 (0.00%)	0	1/142 (0.70%)	1
Infectious pleural effusion † 1	0/135 (0.00%)	0	1/142 (0.70%)	1
Lower respiratory tract infection † 1	0/135 (0.00%)	0	1/142 (0.70%)	1
Lung infection † 1	0/135 (0.00%)	0	1/142 (0.70%)	1
Pharyngitis † 1	0/135 (0.00%)	0	1/142 (0.70%)	1
Pneumonia † 1	3/135 (2.22%)	3	10/142 (7.04%)	13
Respiratory tract infection † 1	0/135 (0.00%)	0	1/142 (0.70%)	1
Respiratory tract infection bacterial † 1	0/135 (0.00%)	0	1/142 (0.70%)	1
Sepsis † 1	3/135 (2.22%)	5	0/142 (0.00%)	0
Osteomyelitis † 1	0/135 (0.00%)	0	1/142 (0.70%)	1
Injury, poisoning and procedural complications
Radiation pneumonitis † 1	1/135 (0.74%)	1	0/142 (0.00%)	0
Investigations
Alanine aminotransferase increased † 1	0/135 (0.00%)	0	1/142 (0.70%)	1
Aspartate aminotransferase increased † 1	0/135 (0.00%)	0	2/142 (1.41%)	2
Neutrophil count decreased † 1	1/135 (0.74%)	1	0/142 (0.00%)	0
Urine output decreased † 1	1/135 (0.74%)	1	0/142 (0.00%)	0
Metabolism and nutrition disorders
Dehydration † 1	1/135 (0.74%)	1	0/142 (0.00%)	0
Hyperglycaemia † 1	1/135 (0.74%)	1	0/142 (0.00%)	0
Type 2 diabetes mellitus † 1	1/135 (0.74%)	1	0/142 (0.00%)	0
Cachexia † 1	0/135 (0.00%)	0	1/142 (0.70%)	1
Musculoskeletal and connective tissue disorders
Arthralgia † 1	0/135 (0.00%)	0	1/142 (0.70%)	1
Back pain † 1	1/135 (0.74%)	1	0/142 (0.00%)	0
Myalgia † 1	0/135 (0.00%)	0	1/142 (0.70%)	1
Spinal osteoarthritis † 1	0/135 (0.00%)	0	1/142 (0.70%)	1
Thoracic Spinal Stenosis † 1	1/135 (0.74%)	1	0/142 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain † 1	1/135 (0.74%)	1	0/142 (0.00%)	0
Tumour associated fever † 1	1/135 (0.74%)	1	0/142 (0.00%)	0
Nervous system disorders
Hypoaesthesia † 1	1/135 (0.74%)	1	0/142 (0.00%)	0
Paraesthesia † 1	1/135 (0.74%)	1	0/142 (0.00%)	0
Peripheral sensory neuropathy † 1	0/135 (0.00%)	0	1/142 (0.70%)	1
Headache † 1	0/135 (0.00%)	0	1/142 (0.70%)	1
Cerebrovascular Accident † 1	0/135 (0.00%)	0	1/142 (0.70%)	1
Product Issues
Device Dislocation † 1	0/135 (0.00%)	0	1/142 (0.70%)	1
Psychiatric disorders
Confusional state † 1	0/135 (0.00%)	0	1/142 (0.70%)	1
Delirium † 1	1/135 (0.74%)	1	0/142 (0.00%)	0
Renal and urinary disorders
Acute kidney injury † 1	1/135 (0.74%)	1	1/142 (0.70%)	1
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome † 1	1/135 (0.74%)	2	0/142 (0.00%)	0
Chronic obstructive pulmonary disease † 1	2/135 (1.48%)	2	0/142 (0.00%)	0
Dyspnoea † 1	1/135 (0.74%)	1	8/142 (5.63%)	8
Haemoptysis † 1	3/135 (2.22%)	3	1/142 (0.70%)	1
Hypoxia † 1	0/135 (0.00%)	0	2/142 (1.41%)	2
Pleural effusion † 1	0/135 (0.00%)	0	4/142 (2.82%)	4
Pleurisy † 1	0/135 (0.00%)	0	1/142 (0.70%)	1
Pneumonitis † 1	0/135 (0.00%)	0	1/142 (0.70%)	2
Pneumothorax † 1	0/135 (0.00%)	0	2/142 (1.41%)	3
Pulmonary embolism † 1	6/135 (4.44%)	6	2/142 (1.41%)	2
Skin and subcutaneous tissue disorders
Rash † 1	0/135 (0.00%)	0	2/142 (1.41%)	2
Vascular disorders
Embolism † 1	0/135 (0.00%)	0	1/142 (0.70%)	1
Peripheral embolism † 1	1/135 (0.74%)	1	0/142 (0.00%)	0
Peripheral ischaemia † 1	1/135 (0.74%)	2	0/142 (0.00%)	0
Superior vena cava syndrome † 1	0/135 (0.00%)	0	1/142 (0.70%)	1
Venous stenosis † 1	0/135 (0.00%)	0	1/142 (0.70%)	1
1 Term from vocabulary, MedDRA (21.1); † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Docetaxel		Atezolizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	125/135 (92.59%)		127/142 (89.44%)
Blood and lymphatic system disorders
Anaemia † 1	27/135 (20.00%)	38	28/142 (19.72%)	53
Neutropenia † 1	15/135 (11.11%)	23	3/142 (2.11%)	4
Endocrine disorders
Hypothyroidism † 1	0/135 (0.00%)	0	13/142 (9.15%)	14
Eye disorders
Lacrimation increased † 1	7/135 (5.19%)	9	1/142 (0.70%)	1
Gastrointestinal disorders
Constipation † 1	32/135 (23.70%)	34	32/142 (22.54%)	33
Diarrhoea † 1	38/135 (28.15%)	51	25/142 (17.61%)	38
Dyspepsia † 1	7/135 (5.19%)	7	4/142 (2.82%)	4
Gastrooesophageal reflux disease † 1	7/135 (5.19%)	8	8/142 (5.63%)	12
Nausea † 1	45/135 (33.33%)	64	32/142 (22.54%)	45
Stomatitis † 1	9/135 (6.67%)	9	3/142 (2.11%)	3
Vomiting † 1	18/135 (13.33%)	20	20/142 (14.08%)	26
General disorders
Asthenia † 1	22/135 (16.30%)	28	16/142 (11.27%)	26
Chest pain † 1	6/135 (4.44%)	8	12/142 (8.45%)	13
Fatigue † 1	55/135 (40.74%)	87	55/142 (38.73%)	82
Oedema peripheral † 1	13/135 (9.63%)	18	9/142 (6.34%)	11
Pain † 1	10/135 (7.41%)	11	6/142 (4.23%)	7
Pyrexia † 1	16/135 (11.85%)	19	23/142 (16.20%)	28
Influenza like illness † 1	2/135 (1.48%)	2	8/142 (5.63%)	10
Chills † 1	4/135 (2.96%)	4	8/142 (5.63%)	9
Infections and infestations
Upper respiratory tract infection † 1	3/135 (2.22%)	5	12/142 (8.45%)	17
Investigations
Weight decreased † 1	11/135 (8.15%)	11	20/142 (14.08%)	24
Alanine Aminotransferase Increased † 1	0/135 (0.00%)	0	8/142 (5.63%)	16
Aspartate Aminotransferase Increased † 1	1/135 (0.74%)	1	10/142 (7.04%)	21
Metabolism and nutrition disorders
Decreased appetite † 1	29/135 (21.48%)	37	51/142 (35.92%)	60
Dehydration † 1	11/135 (8.15%)	11	6/142 (4.23%)	8
Hypokalaemia † 1	4/135 (2.96%)	4	9/142 (6.34%)	12
Hyponatraemia † 1	4/135 (2.96%)	4	9/142 (6.34%)	15
Hypomagnesaemia † 1	6/135 (4.44%)	7	10/142 (7.04%)	15
Musculoskeletal and connective tissue disorders
Arthralgia † 1	12/135 (8.89%)	16	23/142 (16.20%)	28
Back pain † 1	10/135 (7.41%)	11	21/142 (14.79%)	22
Musculoskeletal chest pain † 1	4/135 (2.96%)	5	9/142 (6.34%)	13
Musculoskeletal pain † 1	8/135 (5.93%)	8	20/142 (14.08%)	20
Myalgia † 1	18/135 (13.33%)	24	9/142 (6.34%)	10
Pain in extremity † 1	14/135 (10.37%)	19	10/142 (7.04%)	12
Nervous system disorders
Dizziness † 1	11/135 (8.15%)	12	10/142 (7.04%)	16
Headache † 1	10/135 (7.41%)	10	15/142 (10.56%)	18
Neuropathy peripheral † 1	17/135 (12.59%)	21	4/142 (2.82%)	7
Peripheral sensory neuropathy † 1	12/135 (8.89%)	21	1/142 (0.70%)	2
Psychiatric disorders
Insomnia † 1	11/135 (8.15%)	12	24/142 (16.90%)	26
Respiratory, thoracic and mediastinal disorders
Cough † 1	33/135 (24.44%)	40	45/142 (31.69%)	61
Dyspnoea † 1	27/135 (20.00%)	32	35/142 (24.65%)	41
Dyspnoea exertional † 1	3/135 (2.22%)	3	11/142 (7.75%)	12
Haemoptysis † 1	6/135 (4.44%)	10	15/142 (10.56%)	21
Productive cough † 1	2/135 (1.48%)	2	10/142 (7.04%)	14
Skin and subcutaneous tissue disorders
Alopecia † 1	52/135 (38.52%)	57	3/142 (2.11%)	3
Dry skin † 1	10/135 (7.41%)	10	5/142 (3.52%)	6
Nail disorder † 1	9/135 (6.67%)	9	1/142 (0.70%)	1
Pruritus † 1	6/135 (4.44%)	6	16/142 (11.27%)	26
Rash † 1	16/135 (11.85%)	19	15/142 (10.56%)	30
Vascular disorders
Hypotension † 1	4/135 (2.96%)	4	9/142 (6.34%)	9
1 Term from vocabulary, MedDRA (21.1); † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.

Results Point of Contact

• Name/Title: Medical Communications
• Organization: Hoffmann-La Roche
• Phone: 800 821 ext 8590
• EMail: genentech@druginfo.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Shemesh CS, Chan P, Legrand FA, Shames DS, Das Thakur M, Shi J, Bailey L, Vadhavkar S, He X, Zhang W, Bruno R. Pan-cancer population pharmacokinetics and exposure-safety and -efficacy analyses of atezolizumab in patients with high tumor mutational burden. Pharmacol Res Perspect. 2020 Dec;8(6):e00685. doi: 10.1002/prp2.685.

Chalabi M, Cardona A, Nagarkar DR, Dhawahir Scala A, Gandara DR, Rittmeyer A, Albert ML, Powles T, Kok M, Herrera FG; imCORE working group of early career investigators. Efficacy of chemotherapy and atezolizumab in patients with non-small-cell lung cancer receiving antibiotics and proton pump inhibitors: pooled post hoc analyses of the OAK and POPLAR trials. Ann Oncol. 2020 Apr;31(4):525-531. doi: 10.1016/j.annonc.2020.01.006. Epub 2020 Jan 16.

Fehlings M, Jhunjhunwala S, Kowanetz M, O'Gorman WE, Hegde PS, Sumatoh H, Lee BH, Nardin A, Becht E, Flynn S, Ballinger M, Newell EW, Yadav M. Late-differentiated effector neoantigen-specific CD8+ T cells are enriched in peripheral blood of non-small cell lung carcinoma patients responding to atezolizumab treatment. J Immunother Cancer. 2019 Sep 12;7(1):249. doi: 10.1186/s40425-019-0695-9.

Fehrenbacher L, Spira A, Ballinger M, Kowanetz M, Vansteenkiste J, Mazieres J, Park K, Smith D, Artal-Cortes A, Lewanski C, Braiteh F, Waterkamp D, He P, Zou W, Chen DS, Yi J, Sandler A, Rittmeyer A; POPLAR Study Group. Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet. 2016 Apr 30;387(10030):1837-46. doi: 10.1016/S0140-6736(16)00587-0. Epub 2016 Mar 10.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01903993
• Other Study ID Numbers: GO28753; 2013-001142-34 ( EudraCT Number )
• First Submitted: July 17, 2013
• First Posted: July 19, 2013
• Results First Submitted: November 16, 2016
• Results First Posted: May 23, 2017
• Last Update Posted: October 2, 2019