Trial Outcomes & Findings for Safety and Efficacy Study of Avastin in Locally Advanced Metastatic or Recurrent Non-small Lung Cancer (NSLC) Participants (NCT NCT02596958)

Last Updated: 2016-04-04

Results Overview

ADRs were defined as any response to a drug which was noxious and unintended, and which occurred at dose normally used related to the pharmacological properties. Serious ADRs were defined as any untoward medical occurrence or effect that at any dose resulted in death or life-threatening conditions or required hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, congenital anomaly or birth defect or medically important condition. Toxicity was defined as an adverse event that had an attribution (the relationship to investigational agent) of possible, probable or definite. Avastin-related ADRs (an adverse event with a possible relationship or a relationship to the treatment with AVASTIN) were due to Avastin. ADRs includes serious as well as non-serious ADRs.

Recruitment status

COMPLETED

Target enrollment

996 participants

Primary outcome timeframe

Up to 74 months

Results posted on

2016-04-04

Participant Flow

Participant milestones

Participant milestones
Measure	Bevacizumab Participants received bevacizumab (Avastin) in addition to platinum based chemotherapy for up to 6 cycles (21-day cycles) followed by bevacizumab as a single agent until disease progression. The dose and administration schedule was at the discretion of the treating physician and as per the recommendations given in the current summary of product characteristics (SmPC).
Overall Study STARTED	996
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	996

Reasons for withdrawal

Reasons for withdrawal
Measure	Bevacizumab Participants received bevacizumab (Avastin) in addition to platinum based chemotherapy for up to 6 cycles (21-day cycles) followed by bevacizumab as a single agent until disease progression. The dose and administration schedule was at the discretion of the treating physician and as per the recommendations given in the current summary of product characteristics (SmPC).
Overall Study Serious Adverse Drug Reactions	44
Overall Study Cancer Progression	441
Overall Study Death From Cancer	112
Overall Study Death From Other Cause	33
Overall Study Refusal of Treatment/Poor Cooperation	61
Overall Study Administrative Reasons/Other	231
Overall Study Lost to Follow-up	33
Overall Study Missing	32
Overall Study Excluded Due to Second Line Treatment	9

Baseline Characteristics

Safety and Efficacy Study of Avastin in Locally Advanced Metastatic or Recurrent Non-small Lung Cancer (NSLC) Participants

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bevacizumab n=987 Participants Participants received bevacizumab (Avastin) in addition to platinum based chemotherapy for up to 6 cycles (21-day cycles) followed by bevacizumab as a single agent until disease progression. The dose and administration schedule was at the discretion of the treating physician and as per the recommendations given in the current SmPC.
Age, Continuous	61.5 years STANDARD_DEVIATION 9.8 • n=5 Participants
Sex/Gender, Customized Female	396 participants n=5 Participants
Sex/Gender, Customized Male	590 participants n=5 Participants
Sex/Gender, Customized Missing	1 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 74 months

Population: Analysis population was defined as all participants included in the observational study, regardless of whether they finished it or not.

Outcome measures

Outcome measures
Measure	Bevacizumab n=987 Participants Participants received bevacizumab (Avastin) in addition to platinum based chemotherapy for up to 6 cycles (21-day cycles) followed by bevacizumab as a single agent until disease progression. The dose and administration schedule was at the discretion of the treating physician and as per the recommendations given in the current SmPC.
Percentage of Participants With Adverse Drug Reactions (ADRs), Toxicities, Avastin-Related ADRs, and Serious ADRs ADRs	88.6 percentage of participants
Percentage of Participants With Adverse Drug Reactions (ADRs), Toxicities, Avastin-Related ADRs, and Serious ADRs Toxicities	88.2 percentage of participants
Percentage of Participants With Adverse Drug Reactions (ADRs), Toxicities, Avastin-Related ADRs, and Serious ADRs Avastin-related ADR	27.0 percentage of participants
Percentage of Participants With Adverse Drug Reactions (ADRs), Toxicities, Avastin-Related ADRs, and Serious ADRs Serious ADR	11.1 percentage of participants

SECONDARY outcome

Timeframe: Up to 74 months

Population: Analysis population was defined as all participants included in the observational study, regardless of whether they finished it.

Percentage of participants who withdrew treatment or experienced at least 1 dose deviation in relation to the planned Avastin therapy were reported.

Outcome measures

Outcome measures
Measure	Bevacizumab n=987 Participants Participants received bevacizumab (Avastin) in addition to platinum based chemotherapy for up to 6 cycles (21-day cycles) followed by bevacizumab as a single agent until disease progression. The dose and administration schedule was at the discretion of the treating physician and as per the recommendations given in the current SmPC.
Percentage of Participants Who Withdrew or Modified Treatment	8.8 percentage of participants

SECONDARY outcome

Timeframe: Up to 74 months

Population: Analysis population was defined as all participants included in the observational study, regardless of whether they finished it.

Number of cycles of systemic therapy was the mean number of cycles received by participants in combination therapy with Avastin and chemotherapy and with Avastin monotherapy (maintenance).

Outcome measures

Outcome measures
Measure	Bevacizumab n=987 Participants Participants received bevacizumab (Avastin) in addition to platinum based chemotherapy for up to 6 cycles (21-day cycles) followed by bevacizumab as a single agent until disease progression. The dose and administration schedule was at the discretion of the treating physician and as per the recommendations given in the current SmPC.
Number of Cycles of Systemic Therapy Total number of cycles	7.6 cycles Standard Deviation 7.0
Number of Cycles of Systemic Therapy Number of cycles with combination therapy	4.2 cycles Standard Deviation 1.8
Number of Cycles of Systemic Therapy Number of cycles with maintenance therapy	3.4 cycles Standard Deviation 6.2

SECONDARY outcome

Timeframe: Up to 74 months

Population: Analysis population was defined as all participants included in the observational study, regardless of whether they finished it. Here, number of participants analyzed = participants with non-missing tumor response data.

Best tumor response (assessed as per clinical routine of the individual center) was categorized according to the following criteria at the investigator discretion: complete response (CR: commonly defined as disappearance of all target lesions, all non-target lesions, and no new lesion), partial response (PR: commonly defined as at least a 30 percent \[%\] decrease in the sum of the longest diameter \[LD\] of target lesions, no progression in non-target lesion, and no new lesion), stable disease (SD: commonly defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease \[PD\], in addition to no new target lesions). PD: commonly defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started and not evaluable (NE).

Outcome measures

Outcome measures
Measure	Bevacizumab n=976 Participants Participants received bevacizumab (Avastin) in addition to platinum based chemotherapy for up to 6 cycles (21-day cycles) followed by bevacizumab as a single agent until disease progression. The dose and administration schedule was at the discretion of the treating physician and as per the recommendations given in the current SmPC.
Percentage of Participants With Best Tumor Response Over Time PR	43.3 percentage of participants
Percentage of Participants With Best Tumor Response Over Time CR	2.3 percentage of participants
Percentage of Participants With Best Tumor Response Over Time SD	29.4 percentage of participants
Percentage of Participants With Best Tumor Response Over Time PD	10.1 percentage of participants
Percentage of Participants With Best Tumor Response Over Time NE	14.9 percentage of participants

SECONDARY outcome

Timeframe: Up to 74 months

ECOG Performance Status measured on-therapy (time between first dose and last dose date with a 30-day lag) assessed participant's performance status on 5 point scale: 0 is equal to (=) fully active/able to carry on all pre-disease activities without restriction; 1=restricted in physically strenuous activity, ambulatory/able to carry out light or sedentary work; 2=ambulatory (greater than \[\>\] 50% of waking hours \[hrs\]), capable of all self care, unable to carry out any work activities; 3=capable of only limited self care, confined to bed/chair \>50% of waking hrs; 4=completely disabled, cannot carry on any self care, totally confined to bed/chair; 5=dead.

Outcome measures

Outcome measures
Measure	Bevacizumab n=806 Participants Participants received bevacizumab (Avastin) in addition to platinum based chemotherapy for up to 6 cycles (21-day cycles) followed by bevacizumab as a single agent until disease progression. The dose and administration schedule was at the discretion of the treating physician and as per the recommendations given in the current SmPC.
Percentage of Participants With Eastern Cooperative Group(ECOG) Performance Status Grades Grade 0	18.7 percentage of participants
Percentage of Participants With Eastern Cooperative Group(ECOG) Performance Status Grades Grade 1	50.1 percentage of participants
Percentage of Participants With Eastern Cooperative Group(ECOG) Performance Status Grades Grade 2	23.2 percentage of participants
Percentage of Participants With Eastern Cooperative Group(ECOG) Performance Status Grades Grade 3	6.2 percentage of participants
Percentage of Participants With Eastern Cooperative Group(ECOG) Performance Status Grades Grade 4	1.7 percentage of participants

SECONDARY outcome

Timeframe: Up to 74 months

Disease control was defined as having achieved CR (commonly defined as disappearance of all target lesions, all non-target lesions, and no new lesion), PR (commonly defined as at least a 30% decrease in the sum of the LD of target lesions, no progression in non-target lesion, and no new lesion), or SD (commonly defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, in addition to no new target lesions) during the course of observation which were assessed as per investigator discretion. PD: commonly defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started and NE.

Outcome measures

Outcome measures
Measure	Bevacizumab n=976 Participants Participants received bevacizumab (Avastin) in addition to platinum based chemotherapy for up to 6 cycles (21-day cycles) followed by bevacizumab as a single agent until disease progression. The dose and administration schedule was at the discretion of the treating physician and as per the recommendations given in the current SmPC.
Percentage of Participants With Disease Control	75.0 percentage of participants

SECONDARY outcome

Timeframe: Up to 74 months

PFS was defined as the time (months) between the start of therapy and progression (unequivocal progression of existing non-target lesions) or death. Progression: at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started. PFS was estimated using Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Bevacizumab n=941 Participants Participants received bevacizumab (Avastin) in addition to platinum based chemotherapy for up to 6 cycles (21-day cycles) followed by bevacizumab as a single agent until disease progression. The dose and administration schedule was at the discretion of the treating physician and as per the recommendations given in the current SmPC.
Progression Free Survival (PFS)	7.4 months Interval 7.1 to 8.4

SECONDARY outcome

Timeframe: Up to 74 months

Outcome measures

Outcome measures
Measure	Bevacizumab n=975 Participants Participants received bevacizumab (Avastin) in addition to platinum based chemotherapy for up to 6 cycles (21-day cycles) followed by bevacizumab as a single agent until disease progression. The dose and administration schedule was at the discretion of the treating physician and as per the recommendations given in the current SmPC.
Percentage of Participants Who Died	17.5 percentage of participants

SECONDARY outcome

Timeframe: Up to 74 months

Population: Analysis population was defined as all participants included in the observational study, regardless of whether they finished it. Here 'number of participants analyzed' = participants assessed for this outcome measure.

Overall survival was defined as the time (months) between the start of therapy and the date of death.

Outcome measures

Outcome measures
Measure	Bevacizumab n=975 Participants Participants received bevacizumab (Avastin) in addition to platinum based chemotherapy for up to 6 cycles (21-day cycles) followed by bevacizumab as a single agent until disease progression. The dose and administration schedule was at the discretion of the treating physician and as per the recommendations given in the current SmPC.
Overall Survival	18.4 months Standard Deviation 0.5

Adverse Events

Bevacizumab

Serious events: 110 serious events

Other events: 851 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Bevacizumab n=987 participants at risk Participants received bevacizumab (Avastin) in addition to platinum based chemotherapy for up to 6 cycles (21-day cycles) followed by bevacizumab as a single agent until disease progression. The dose and administration schedule was at the discretion of the treating physician and as per the recommendations given in the current SmPC.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.5% 15/987 • Up to the end of study (median duration of 170.8 days)
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.71% 7/987 • Up to the end of study (median duration of 170.8 days)
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.51% 5/987 • Up to the end of study (median duration of 170.8 days)
Respiratory, thoracic and mediastinal disorders Acquired tracheo-oesophageal fistula	0.10% 1/987 • Up to the end of study (median duration of 170.8 days)
Respiratory, thoracic and mediastinal disorders Bronchial haemorrhage	0.10% 1/987 • Up to the end of study (median duration of 170.8 days)
Respiratory, thoracic and mediastinal disorders Oesophagobronchial fistula	0.10% 1/987 • Up to the end of study (median duration of 170.8 days)
Respiratory, thoracic and mediastinal disorders Pleural fistula	0.10% 1/987 • Up to the end of study (median duration of 170.8 days)
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	0.10% 1/987 • Up to the end of study (median duration of 170.8 days)
Vascular disorders Hypertension	1.5% 15/987 • Up to the end of study (median duration of 170.8 days)
Vascular disorders Haemorrhage	0.10% 1/987 • Up to the end of study (median duration of 170.8 days)
Infections and infestations Pneumonia	0.91% 9/987 • Up to the end of study (median duration of 170.8 days)
Infections and infestations Sepsis	0.41% 4/987 • Up to the end of study (median duration of 170.8 days)
Infections and infestations Peritonitis	0.30% 3/987 • Up to the end of study (median duration of 170.8 days)
Gastrointestinal disorders Large intestine perforation	0.41% 4/987 • Up to the end of study (median duration of 170.8 days)
Gastrointestinal disorders Nausea	0.30% 3/987 • Up to the end of study (median duration of 170.8 days)
Gastrointestinal disorders Gastrointestinal haemorrhage	0.10% 1/987 • Up to the end of study (median duration of 170.8 days)
Gastrointestinal disorders Gastrointestinal perforation	0.10% 1/987 • Up to the end of study (median duration of 170.8 days)
Gastrointestinal disorders Large intestinal haemorrhage	0.10% 1/987 • Up to the end of study (median duration of 170.8 days)
Gastrointestinal disorders Rectal haemorrhage	0.10% 1/987 • Up to the end of study (median duration of 170.8 days)
Gastrointestinal disorders Vomiting	0.10% 1/987 • Up to the end of study (median duration of 170.8 days)
General disorders Death	0.41% 4/987 • Up to the end of study (median duration of 170.8 days)
Blood and lymphatic system disorders Leukopenia	0.51% 5/987 • Up to the end of study (median duration of 170.8 days)
Blood and lymphatic system disorders Anaemia	0.41% 4/987 • Up to the end of study (median duration of 170.8 days)
Blood and lymphatic system disorders Febrile neutropenia	0.20% 2/987 • Up to the end of study (median duration of 170.8 days)
Blood and lymphatic system disorders Neutropenia	0.20% 2/987 • Up to the end of study (median duration of 170.8 days)
Blood and lymphatic system disorders Pancytopenia	0.20% 2/987 • Up to the end of study (median duration of 170.8 days)
Blood and lymphatic system disorders Thrombocytopenia	0.20% 2/987 • Up to the end of study (median duration of 170.8 days)
Blood and lymphatic system disorders Splenic infarction	0.10% 1/987 • Up to the end of study (median duration of 170.8 days)
Nervous system disorders Cerebral haemorrhage	0.30% 3/987 • Up to the end of study (median duration of 170.8 days)
Nervous system disorders Cerebral ischaemia	0.10% 1/987 • Up to the end of study (median duration of 170.8 days)
Cardiac disorders Cardiac failure	0.41% 4/987 • Up to the end of study (median duration of 170.8 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	0.41% 4/987 • Up to the end of study (median duration of 170.8 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	0.20% 2/987 • Up to the end of study (median duration of 170.8 days)
Renal and urinary disorders Proteinuria	0.30% 3/987 • Up to the end of study (median duration of 170.8 days)
Musculoskeletal and connective tissue disorders Fistula	0.20% 2/987 • Up to the end of study (median duration of 170.8 days)

Other adverse events

Other adverse events
Measure	Bevacizumab n=987 participants at risk Participants received bevacizumab (Avastin) in addition to platinum based chemotherapy for up to 6 cycles (21-day cycles) followed by bevacizumab as a single agent until disease progression. The dose and administration schedule was at the discretion of the treating physician and as per the recommendations given in the current SmPC.
Blood and lymphatic system disorders Anaemia	60.2% 594/987 • Up to the end of study (median duration of 170.8 days)
Blood and lymphatic system disorders Leukopenia	49.8% 492/987 • Up to the end of study (median duration of 170.8 days)
Blood and lymphatic system disorders Neutropenia	31.5% 311/987 • Up to the end of study (median duration of 170.8 days)
Blood and lymphatic system disorders Thrombocytopenia	31.1% 307/987 • Up to the end of study (median duration of 170.8 days)
General disorders Pain	17.3% 171/987 • Up to the end of study (median duration of 170.8 days)
General disorders Pyrexia	10.3% 102/987 • Up to the end of study (median duration of 170.8 days)
General disorders Chest pain	6.7% 66/987 • Up to the end of study (median duration of 170.8 days)
Vascular disorders Hypertension	13.6% 134/987 • Up to the end of study (median duration of 170.8 days)
Musculoskeletal and connective tissue disorders Pain in extremity	6.9% 68/987 • Up to the end of study (median duration of 170.8 days)
Musculoskeletal and connective tissue disorders Back pain	5.1% 50/987 • Up to the end of study (median duration of 170.8 days)
Nervous system disorders Peripheral sensory neuropathy	11.2% 111/987 • Up to the end of study (median duration of 170.8 days)
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	10.0% 99/987 • Up to the end of study (median duration of 170.8 days)
Respiratory, thoracic and mediastinal disorders Epistaxis	6.2% 61/987 • Up to the end of study (median duration of 170.8 days)
Renal and urinary disorders Proteinuria	5.7% 56/987 • Up to the end of study (median duration of 170.8 days)
Gastrointestinal disorders Nausea	46.5% 459/987 • Up to the end of study (median duration of 170.8 days)
Gastrointestinal disorders Vomiting	18.7% 185/987 • Up to the end of study (median duration of 170.8 days)
Gastrointestinal disorders Diarrhoea	10.0% 99/987 • Up to the end of study (median duration of 170.8 days)

Additional Information

Medical Communications

Hoffmann-LaRoche

Phone: 800-821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER