Trial Outcomes & Findings for A Study to Assess Biomarkers Impact on Participants Response to Erlotinib Treatment for First-line Non-Small Cell Lung Cancer With Endothelial Growth Factor Receptor (EGFR) Activating Mutations (NCT NCT01153984)

Last Updated: 2017-04-13

Results Overview

PFS was the time from inclusion in the study to the date of first documented PD or death from any cause, whichever occurred first. Participants without event were censored at the date of the last tumor assessment where non-progression was documented. If a participant received a second anti-cancer therapy without prior documentation of disease progression, the participant was censored at the date of last tumor assessment before starting new chemotherapy. Analysis was performed using Kaplan-Meier method. PD was defined as at least a 20% increase in the sum of LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

23 participants

Primary outcome timeframe

Baseline up to approximately 4 years

Results posted on

2017-04-13

Participant Flow

Ninety participants were screened and 23 participants were enrolled.

Participant milestones

Participant milestones
Measure	Erlotinib Participants received 150 milligrams (mg) erlotinib orally daily until disease progression, unacceptable toxicity, withdrawal due to any reason or death.
Overall Study STARTED	23
Overall Study COMPLETED	21
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Erlotinib Participants received 150 milligrams (mg) erlotinib orally daily until disease progression, unacceptable toxicity, withdrawal due to any reason or death.
Overall Study Withdrawal by Subject	1
Overall Study Adverse Event	1

Baseline Characteristics

A Study to Assess Biomarkers Impact on Participants Response to Erlotinib Treatment for First-line Non-Small Cell Lung Cancer With Endothelial Growth Factor Receptor (EGFR) Activating Mutations

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Erlotinib n=23 Participants Participants received 150 mg erlotinib orally daily until disease progression, unacceptable toxicity, withdrawal due to any reason or death.
Age, Continuous	55.52 Years STANDARD_DEVIATION 11.59 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to approximately 4 years

Population: All enrolled participants.

Outcome measures

Outcome measures
Measure	Erlotinib n=23 Participants Participants received 150 mg erlotinib orally daily until disease progression, unacceptable toxicity, withdrawal due to any reason or death.
Progression-Free Survival (PFS), as Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)	387.000 days 95% Confidence Interval 85.32 • Interval 103.592 to 670.408

SECONDARY outcome

Timeframe: Baseline up to approximately 4 years

Population: All enrolled participants.

Time to disease progression was defined as the time from baseline evaluation to the first date PD was recorded. Participants without progression were censored at the date of last tumor assessment where non-progression was documented. PD was defined as at least a 20% increase in the sum of LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions.

Outcome measures

Outcome measures
Measure	Erlotinib n=23 Participants Participants received 150 mg erlotinib orally daily until disease progression, unacceptable toxicity, withdrawal due to any reason or death.
Time to Disease Progression, as Assessed by Investigator Using RECIST v1.1	193.00 days 95% Confidence Interval 70.323 • Interval 57.137 to 328.863

SECONDARY outcome

Timeframe: Baseline up to approximately 4 years

Population: All enrolled participants.

CR was defined as the disappearance of all target lesions, and PR was defined as at least a 30% decrease in the sum of the longest diameter compared to baseline.

Outcome measures

Outcome measures
Measure	Erlotinib n=23 Participants Participants received 150 mg erlotinib orally daily until disease progression, unacceptable toxicity, withdrawal due to any reason or death.
Percentage of Participants With Complete Response (CR) And Partial Response (PR) as Assessed by the Investigator Using RECIST v1.1 CR	0 percentage of participants
Percentage of Participants With Complete Response (CR) And Partial Response (PR) as Assessed by the Investigator Using RECIST v1.1 PR	8.7 percentage of participants

SECONDARY outcome

Timeframe: Year 1

Population: All enrolled participants with available data for this outcome.

Outcome measures

Outcome measures
Measure	Erlotinib n=21 Participants Participants received 150 mg erlotinib orally daily until disease progression, unacceptable toxicity, withdrawal due to any reason or death.
Percentage of Participants Who Were Alive One Year After Study Treatment Initiation	85.7 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to approximately 4 years

Population: All enrolled participants with available data for this outcome.

PD was assessed using RECIST v1.1. PD was defined as at least a 20% increase in the sum of LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions. Percentage of participants by localization of PD were reported. Localization included: Left lung inferior lobe; Para-aortic; Left lung upper lobe; Right lung inferior lobe; and Infracranial.

Outcome measures

Outcome measures
Measure	Erlotinib n=21 Participants Participants received 150 mg erlotinib orally daily until disease progression, unacceptable toxicity, withdrawal due to any reason or death.
Percentage of Participants by Localization of PD, as Assessed by Investigator Using RECIST v1.1 Left lung inferior lobe	24 percentage of participants
Percentage of Participants by Localization of PD, as Assessed by Investigator Using RECIST v1.1 Para-aortic	14 percentage of participants
Percentage of Participants by Localization of PD, as Assessed by Investigator Using RECIST v1.1 Left lung upper lobe	10 percentage of participants
Percentage of Participants by Localization of PD, as Assessed by Investigator Using RECIST v1.1 Right lung inferior lobe	14 percentage of participants
Percentage of Participants by Localization of PD, as Assessed by Investigator Using RECIST v1.1 Infracranial	38 percentage of participants

SECONDARY outcome

Timeframe: Day 1

Population: All enrolled participants.

Participants were asked: "Have you smoked at least 100 cigarettes in your entire life?" and "Do you now smoke cigarettes every day, some days, or not at all?" Responses were grouped into three categories: Current Smoker, Former Smoker, and Non-Smoker. Participants who reported smoking at least 100 cigarettes in their lifetime and who, at the time of survey, smoked either every day or some days were defined as 'Current smoker'. Participants who reported smoking at least 100 cigarettes in their lifetime and who, at the time of the survey, did not smoke at all were defined as 'Former smoker'. Participants who reported never having smoked 100 cigarettes were defined as 'Non-smoker'.

Outcome measures

Outcome measures
Measure	Erlotinib n=23 Participants Participants received 150 mg erlotinib orally daily until disease progression, unacceptable toxicity, withdrawal due to any reason or death.
Number of EGFR Positive Participants Classified Based on Smoking Status Non-smoker	17 participants
Number of EGFR Positive Participants Classified Based on Smoking Status Former smoker	3 participants
Number of EGFR Positive Participants Classified Based on Smoking Status Current smoker	3 participants

SECONDARY outcome

Timeframe: Day 1

Population: All enrolled participants.

Participants with NSCLC have tumor associated with EGFR mutations. These mutations occur within EGFR Exons 18-21, which encodes a portion of the EGFR kinase domain.

Outcome measures

Outcome measures
Measure	Erlotinib n=23 Participants Participants received 150 mg erlotinib orally daily until disease progression, unacceptable toxicity, withdrawal due to any reason or death.
Number of EGFR Positive Participants Classified Based on Type of EGFR Mutations Exon 19 deletions	20 participants
Number of EGFR Positive Participants Classified Based on Type of EGFR Mutations Exon 21 L858R mutations	3 participants

SECONDARY outcome

Timeframe: Baseline up to approximately 4 years

Population: No participants were analyzed for this outcome as no plasma samples were collected during the study.

Outcome measures

Outcome data not reported

Adverse Events

Erlotinib

Serious events: 5 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Erlotinib n=23 participants at risk Participants received 150 mg erlotinib orally daily until disease progression, unacceptable toxicity, withdrawal due to any reason or death.
Nervous system disorders Hemiparesis	4.3% 1/23 • Baseline up to approximately 4 years Safety analysis population included all participants who receive at least one dose of treatment and had at least one monthly assessment.
Nervous system disorders Brain neoplasm malignant	4.3% 1/23 • Baseline up to approximately 4 years Safety analysis population included all participants who receive at least one dose of treatment and had at least one monthly assessment.
Infections and infestations Respiratory tract infection	4.3% 1/23 • Baseline up to approximately 4 years Safety analysis population included all participants who receive at least one dose of treatment and had at least one monthly assessment.
Cardiac disorders Atrial fibrillation	4.3% 1/23 • Baseline up to approximately 4 years Safety analysis population included all participants who receive at least one dose of treatment and had at least one monthly assessment.
Cardiac disorders Pericardial effusion	4.3% 1/23 • Baseline up to approximately 4 years Safety analysis population included all participants who receive at least one dose of treatment and had at least one monthly assessment.
Respiratory, thoracic and mediastinal disorders Pleural effusion	4.3% 1/23 • Baseline up to approximately 4 years Safety analysis population included all participants who receive at least one dose of treatment and had at least one monthly assessment.
Vascular disorders Ischemic stroke	4.3% 1/23 • Baseline up to approximately 4 years Safety analysis population included all participants who receive at least one dose of treatment and had at least one monthly assessment.

Other adverse events

Other adverse events
Measure	Erlotinib n=23 participants at risk Participants received 150 mg erlotinib orally daily until disease progression, unacceptable toxicity, withdrawal due to any reason or death.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	4.3% 1/23 • Baseline up to approximately 4 years Safety analysis population included all participants who receive at least one dose of treatment and had at least one monthly assessment.
Gastrointestinal disorders Vomiting	4.3% 1/23 • Baseline up to approximately 4 years Safety analysis population included all participants who receive at least one dose of treatment and had at least one monthly assessment.
Gastrointestinal disorders Diarrhoea	13.0% 3/23 • Baseline up to approximately 4 years Safety analysis population included all participants who receive at least one dose of treatment and had at least one monthly assessment.
Gastrointestinal disorders Nausea	4.3% 1/23 • Baseline up to approximately 4 years Safety analysis population included all participants who receive at least one dose of treatment and had at least one monthly assessment.
Gastrointestinal disorders Abdominal pain	4.3% 1/23 • Baseline up to approximately 4 years Safety analysis population included all participants who receive at least one dose of treatment and had at least one monthly assessment.
Gastrointestinal disorders Dyspepsia	4.3% 1/23 • Baseline up to approximately 4 years Safety analysis population included all participants who receive at least one dose of treatment and had at least one monthly assessment.
Nervous system disorders Headache	4.3% 1/23 • Baseline up to approximately 4 years Safety analysis population included all participants who receive at least one dose of treatment and had at least one monthly assessment.
Reproductive system and breast disorders Vaginal hemorrhages	4.3% 1/23 • Baseline up to approximately 4 years Safety analysis population included all participants who receive at least one dose of treatment and had at least one monthly assessment.
Respiratory, thoracic and mediastinal disorders Cough	4.3% 1/23 • Baseline up to approximately 4 years Safety analysis population included all participants who receive at least one dose of treatment and had at least one monthly assessment.
Respiratory, thoracic and mediastinal disorders Pharyngeal inflammation	4.3% 1/23 • Baseline up to approximately 4 years Safety analysis population included all participants who receive at least one dose of treatment and had at least one monthly assessment.
Respiratory, thoracic and mediastinal disorders Dyspnea	4.3% 1/23 • Baseline up to approximately 4 years Safety analysis population included all participants who receive at least one dose of treatment and had at least one monthly assessment.
Injury, poisoning and procedural complications Arthropod bite	4.3% 1/23 • Baseline up to approximately 4 years Safety analysis population included all participants who receive at least one dose of treatment and had at least one monthly assessment.
General disorders Fatigue	4.3% 1/23 • Baseline up to approximately 4 years Safety analysis population included all participants who receive at least one dose of treatment and had at least one monthly assessment.
General disorders Pyrexia	34.8% 8/23 • Baseline up to approximately 4 years Safety analysis population included all participants who receive at least one dose of treatment and had at least one monthly assessment.
General disorders Chest pain	4.3% 1/23 • Baseline up to approximately 4 years Safety analysis population included all participants who receive at least one dose of treatment and had at least one monthly assessment.
Musculoskeletal and connective tissue disorders Back pain	4.3% 1/23 • Baseline up to approximately 4 years Safety analysis population included all participants who receive at least one dose of treatment and had at least one monthly assessment.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	4.3% 1/23 • Baseline up to approximately 4 years Safety analysis population included all participants who receive at least one dose of treatment and had at least one monthly assessment.
Investigations Transaminases increased	4.3% 1/23 • Baseline up to approximately 4 years Safety analysis population included all participants who receive at least one dose of treatment and had at least one monthly assessment.
Skin and subcutaneous tissue disorders Rash	30.4% 7/23 • Baseline up to approximately 4 years Safety analysis population included all participants who receive at least one dose of treatment and had at least one monthly assessment.
Eye disorders Conjunctivitis	4.3% 1/23 • Baseline up to approximately 4 years Safety analysis population included all participants who receive at least one dose of treatment and had at least one monthly assessment.
Cardiac disorders Syncope	4.3% 1/23 • Baseline up to approximately 4 years Safety analysis population included all participants who receive at least one dose of treatment and had at least one monthly assessment.
Respiratory, thoracic and mediastinal disorders Pneumonitis	4.3% 1/23 • Baseline up to approximately 4 years Safety analysis population included all participants who receive at least one dose of treatment and had at least one monthly assessment.
Endocrine disorders Menorrhagia	4.3% 1/23 • Baseline up to approximately 4 years Safety analysis population included all participants who receive at least one dose of treatment and had at least one monthly assessment.

Additional Information

Medical Communications

Hoffmann-La Roche

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