Trial Outcomes & Findings for Erlotinib Hydrochloride With or Without Bevacizumab in Treating Patients With Stage IV Non-small Cell Lung Cancer With Epidermal Growth Factor Receptor Mutations (NCT NCT01532089)

NCT ID: NCT01532089

Last Updated: 2020-10-06

Results Overview

Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as at least a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

88 participants

Primary outcome timeframe

Time from randomization to disease progression and death of any cause, whichever comes first, assessed up to 6 years

Results posted on

2020-10-06

Participant Flow

Participant milestones

Participant milestones
Measure	Arm A (Erlotinib Hydrochloride) Patients receive 150 mg erlotinib hydrochloride PO QD on days 1-21.	Arm B (Erlotinib Hydrochloride, Bevacizumab) Patients receive 150 mg erlotinib hydrochloride as in Arm A and 15 mg/kg bevacizumab IV over 30-90 minutes on day 1.
Overall Study STARTED	45	43
Overall Study COMPLETED	45	43
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Erlotinib Hydrochloride With or Without Bevacizumab in Treating Patients With Stage IV Non-small Cell Lung Cancer With Epidermal Growth Factor Receptor Mutations

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A (Erlotinib Hydrochloride) n=45 Participants Patients receive 150 mg erlotinib hydrochloride PO QD on days 1-21.	Arm B (Erlotinib Hydrochloride, Bevacizumab) n=43 Participants Patients receive 150 mg erlotinib hydrochloride as in Arm A and 15 mg/kg bevacizumab IV over 30-90 minutes on day 1.	Total n=88 Participants Total of all reporting groups
Age, Continuous	63 years n=5 Participants	65 years n=7 Participants	63.5 years n=5 Participants
Sex: Female, Male Female	31 Participants n=5 Participants	31 Participants n=7 Participants	62 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	12 Participants n=7 Participants	26 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) White	39 Participants n=5 Participants	36 Participants n=7 Participants	75 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
ECOG Performance Status 0	19 Participants n=5 Participants	24 Participants n=7 Participants	43 Participants n=5 Participants
ECOG Performance Status 1	26 Participants n=5 Participants	19 Participants n=7 Participants	45 Participants n=5 Participants
EGFR exon mutation Exon 19 deletion	30 Participants n=5 Participants	29 Participants n=7 Participants	59 Participants n=5 Participants
EGFR exon mutation Exon 21 L858R mutation	15 Participants n=5 Participants	14 Participants n=7 Participants	29 Participants n=5 Participants

PRIMARY outcome

Timeframe: Time from randomization to disease progression and death of any cause, whichever comes first, assessed up to 6 years

Outcome measures

Outcome measures
Measure	Arm A (Erlotinib Hydrochloride) n=45 Participants Patients receive 150 mg erlotinib hydrochloride PO QD on days 1-21.	Arm B (Erlotinib Hydrochloride, Bevacizumab) n=43 Participants Patients receive 150 mg erlotinib hydrochloride as in Arm A and 15 mg/kg bevacizumab IV over 30-90 minutes on day 1.
Progression Free Survival (PFS)	13.5 months Interval 8.8 to 21.6	17.9 months Interval 13.3 to 24.1

SECONDARY outcome

Timeframe: Time from randomization to death of any causes, assessed up to 6 years

Overall survival time is defined as the time from randomization to death due to any cause. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.

Outcome measures

Outcome measures
Measure	Arm A (Erlotinib Hydrochloride) n=45 Participants Patients receive 150 mg erlotinib hydrochloride PO QD on days 1-21.	Arm B (Erlotinib Hydrochloride, Bevacizumab) n=43 Participants Patients receive 150 mg erlotinib hydrochloride as in Arm A and 15 mg/kg bevacizumab IV over 30-90 minutes on day 1.
Overall Survival	50.6 months Interval 49.4 to The 95% CI upper limit was not reached (insufficient number of participants with events).	32.4 months Interval 26.9 to 54.4

SECONDARY outcome

Timeframe: Up to 6 years

Population: Patients with tumor response data available were included in this analysis.

The response rate (percentage) is the percent of patients whose best response was Complete Response (CR) or Partial Response (PR) as defined by RECIST 1.1 criteria. Percentage of successes will be estimated by 100 times the number of successes divided by the total number of evaluable patients. (CR: Disappearance of all evidence of disease, PR: Regression of measurable disease and no new sites).

Outcome measures

Outcome measures
Measure	Arm A (Erlotinib Hydrochloride) n=42 Participants Patients receive 150 mg erlotinib hydrochloride PO QD on days 1-21.	Arm B (Erlotinib Hydrochloride, Bevacizumab) n=43 Participants Patients receive 150 mg erlotinib hydrochloride as in Arm A and 15 mg/kg bevacizumab IV over 30-90 minutes on day 1.
Response Rate (Complete or Partial) to Each Treatment, Evaluated Using the New International Criteria Proposed by the Revised Response Evaluation Criteria in Solid Tumors Guidelines (Version 1.1)	83 percentage of patients Interval 69.0 to 93.0	81 percentage of patients Interval 67.0 to 92.0

SECONDARY outcome

Timeframe: From the date of randomization to the date of disease progression or death of any cause, whichever comes first, assessed up to 6 years

Population: This analysis includes all patients with EGFR exon mutation data available and primary endpoint data available.

Outcome measures

Outcome measures
Measure	Arm A (Erlotinib Hydrochloride) n=59 Participants Patients receive 150 mg erlotinib hydrochloride PO QD on days 1-21.	Arm B (Erlotinib Hydrochloride, Bevacizumab) n=29 Participants Patients receive 150 mg erlotinib hydrochloride as in Arm A and 15 mg/kg bevacizumab IV over 30-90 minutes on day 1.
Progression Free Survival of Patients With Different Mutation Types (Exon Deletion 19 Versus Exon 21 L858R)	17.9 months Interval 13.5 to 23.9	12.6 months Interval 9.0 to 24.1

SECONDARY outcome

Timeframe: Up to 42 days after treatment discontinuation

The number of patients experiencing toxicity defined as grade 3 or higher adverse events (using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0) considered at least possibly related to treatment is reported below.

Outcome measures

Outcome measures
Measure	Arm A (Erlotinib Hydrochloride) n=45 Participants Patients receive 150 mg erlotinib hydrochloride PO QD on days 1-21.	Arm B (Erlotinib Hydrochloride, Bevacizumab) n=43 Participants Patients receive 150 mg erlotinib hydrochloride as in Arm A and 15 mg/kg bevacizumab IV over 30-90 minutes on day 1.
Number of Patients Experiencing Toxicity	13 Participants	31 Participants

Adverse Events

Arm A (Erlotinib Hydrochloride)

Serious events: 12 serious events

Other events: 43 other events

Deaths: 23 deaths

Arm B (Erlotinib Hydrochloride, Bevacizumab)

Serious events: 17 serious events

Other events: 43 other events

Deaths: 27 deaths

Serious adverse events

Other adverse events

Additional Information

Thomas E. Stinchcombe, M.D.

Duke University

Phone: 507/284-4565

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Arm A (Erlotinib Hydrochloride) n=45 participants at risk Patients receive 150 mg erlotinib hydrochloride PO QD on days 1-21.	Arm B (Erlotinib Hydrochloride, Bevacizumab) n=43 participants at risk Patients receive 150 mg erlotinib hydrochloride as in Arm A and 15 mg/kg bevacizumab IV over 30-90 minutes on day 1.
Cardiac disorders Acute coronary syndrome	0.00% 0/45 • Up to 42 days after treatment discontinuation	2.3% 1/43 • Number of events 1 • Up to 42 days after treatment discontinuation
Cardiac disorders Chest pain - cardiac	2.2% 1/45 • Number of events 1 • Up to 42 days after treatment discontinuation	2.3% 1/43 • Number of events 1 • Up to 42 days after treatment discontinuation
Gastrointestinal disorders Abdominal pain	2.2% 1/45 • Number of events 1 • Up to 42 days after treatment discontinuation	2.3% 1/43 • Number of events 1 • Up to 42 days after treatment discontinuation
Gastrointestinal disorders Anal hemorrhage	0.00% 0/45 • Up to 42 days after treatment discontinuation	2.3% 1/43 • Number of events 1 • Up to 42 days after treatment discontinuation
Gastrointestinal disorders Diarrhea	4.4% 2/45 • Number of events 2 • Up to 42 days after treatment discontinuation	2.3% 1/43 • Number of events 1 • Up to 42 days after treatment discontinuation
General disorders Sudden death NOS	2.2% 1/45 • Number of events 1 • Up to 42 days after treatment discontinuation	0.00% 0/43 • Up to 42 days after treatment discontinuation
Infections and infestations Kidney infection	0.00% 0/45 • Up to 42 days after treatment discontinuation	2.3% 1/43 • Number of events 1 • Up to 42 days after treatment discontinuation
Infections and infestations Lung infection	4.4% 2/45 • Number of events 3 • Up to 42 days after treatment discontinuation	0.00% 0/43 • Up to 42 days after treatment discontinuation
Infections and infestations Nail infection	0.00% 0/45 • Up to 42 days after treatment discontinuation	2.3% 1/43 • Number of events 1 • Up to 42 days after treatment discontinuation
Infections and infestations Rash pustular	0.00% 0/45 • Up to 42 days after treatment discontinuation	2.3% 1/43 • Number of events 1 • Up to 42 days after treatment discontinuation
Injury, poisoning and procedural complications Fall	0.00% 0/45 • Up to 42 days after treatment discontinuation	2.3% 1/43 • Number of events 1 • Up to 42 days after treatment discontinuation
Investigations Alanine aminotransferase increased	2.2% 1/45 • Number of events 2 • Up to 42 days after treatment discontinuation	0.00% 0/43 • Up to 42 days after treatment discontinuation
Investigations Aspartate aminotransferase increased	2.2% 1/45 • Number of events 2 • Up to 42 days after treatment discontinuation	0.00% 0/43 • Up to 42 days after treatment discontinuation
Investigations Blood bilirubin increased	2.2% 1/45 • Number of events 1 • Up to 42 days after treatment discontinuation	2.3% 1/43 • Number of events 1 • Up to 42 days after treatment discontinuation
Investigations Cardiac troponin I increased	2.2% 1/45 • Number of events 1 • Up to 42 days after treatment discontinuation	0.00% 0/43 • Up to 42 days after treatment discontinuation
Metabolism and nutrition disorders Dehydration	0.00% 0/45 • Up to 42 days after treatment discontinuation	4.7% 2/43 • Number of events 2 • Up to 42 days after treatment discontinuation
Metabolism and nutrition disorders Hyponatremia	0.00% 0/45 • Up to 42 days after treatment discontinuation	2.3% 1/43 • Number of events 1 • Up to 42 days after treatment discontinuation
Nervous system disorders Cognitive disturbance	2.2% 1/45 • Number of events 1 • Up to 42 days after treatment discontinuation	0.00% 0/43 • Up to 42 days after treatment discontinuation
Nervous system disorders Dizziness	2.2% 1/45 • Number of events 1 • Up to 42 days after treatment discontinuation	0.00% 0/43 • Up to 42 days after treatment discontinuation
Nervous system disorders Syncope	0.00% 0/45 • Up to 42 days after treatment discontinuation	2.3% 1/43 • Number of events 1 • Up to 42 days after treatment discontinuation
Psychiatric disorders Confusion	0.00% 0/45 • Up to 42 days after treatment discontinuation	2.3% 1/43 • Number of events 1 • Up to 42 days after treatment discontinuation
Renal and urinary disorders Proteinuria	0.00% 0/45 • Up to 42 days after treatment discontinuation	2.3% 1/43 • Number of events 1 • Up to 42 days after treatment discontinuation
Renal and urinary disorders Urinary retention	2.2% 1/45 • Number of events 1 • Up to 42 days after treatment discontinuation	0.00% 0/43 • Up to 42 days after treatment discontinuation
Respiratory, thoracic and mediastinal disorders Bronchopulmonary hemorrhage	0.00% 0/45 • Up to 42 days after treatment discontinuation	2.3% 1/43 • Number of events 2 • Up to 42 days after treatment discontinuation
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/45 • Up to 42 days after treatment discontinuation	2.3% 1/43 • Number of events 1 • Up to 42 days after treatment discontinuation
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/45 • Up to 42 days after treatment discontinuation	2.3% 1/43 • Number of events 1 • Up to 42 days after treatment discontinuation
Skin and subcutaneous tissue disorders Erythema multiforme	0.00% 0/45 • Up to 42 days after treatment discontinuation	2.3% 1/43 • Number of events 1 • Up to 42 days after treatment discontinuation
Skin and subcutaneous tissue disorders Pain of skin	0.00% 0/45 • Up to 42 days after treatment discontinuation	2.3% 1/43 • Number of events 1 • Up to 42 days after treatment discontinuation
Skin and subcutaneous tissue disorders Rash acneiform	2.2% 1/45 • Number of events 1 • Up to 42 days after treatment discontinuation	7.0% 3/43 • Number of events 3 • Up to 42 days after treatment discontinuation
Vascular disorders Hypertension	8.9% 4/45 • Number of events 4 • Up to 42 days after treatment discontinuation	4.7% 2/43 • Number of events 3 • Up to 42 days after treatment discontinuation
Vascular disorders Thromboembolic event	4.4% 2/45 • Number of events 2 • Up to 42 days after treatment discontinuation	2.3% 1/43 • Number of events 2 • Up to 42 days after treatment discontinuation