First-Line Erlotinib Therapy and the Subsequent Development of Mechanisms of Secondary Resistance in Patients With Non-Small Cell Lung Cancer and Known Sensitizing EGFR Mutations
- Histologically or cytologically confirmed non-small cell lung cancer, stage IV or
IIIB with a malignant pleural or pericardial effusion. Patients with stage I or II
non-small cell lung cancer who have undergone surgical resection but who subsequently
relapse with metastatic disease or a malignant pleural effusion are also eligible.
- Documentation of a sensitizing mutation of the epidermal growth factor receptor. In
addition, there must be a sufficient tissue for analysis of KRAS mutations and MET
- At least one measurable or evaluable site of disease as defined by revised RECIST
(version 1.1) criteria.
- 18 years of age or older
- No more than one prior systemic therapy regimen for advanced non-small cell lung
cancer. Chemotherapy delivered as part of concurrent chemoradiation will also count
as a prior systemic therapy regimen. Adjuvant therapy for resected NSCLC will not
count towards this total as long as it was completed at least 6 months prior to
enrollment and did not include therapy with an EGFR-targeted agent. Adjuvant therapy
completed less than 6 months prior to the time of screening will count as a prior
- 3 or more weeks since prior major surgery
- 2 or more weeks since prior radiation
- ECOG performance status 0-1
- Life expectancy > 8 weeks
- Adequate hematologic, renal, and hepatic function
- Willingness to undergo repeat tumor biopsy at the time of disease progression.
- Untreated and/or uncontrolled central nervous system metastases. Patients with prior
brain metastases must have had definitive treatment (radiation or surgery) and must
be clinically stable off steroids for at least 1 week prior to enrollment.
- More than one prior systemic chemotherapy for advanced non-small cell lung cancer. ,
Chemotherapy delivered as part of concurrent chemoradiation will also count as a
prior systemic therapy regimen. Adjuvant therapy for resected NSCLC willnot count
towards this total as long as it was completed at least 6 months prior to enrollment
and did not include therapy with an EGFR-targeted agent. Adjuvant therapy completed
less than 6 months prior to the time of screening will count as a prior regimen.
- Prior exposure to erlotinib or other treatments targeting the HER family axis.
- Active malignancies within the past 3 years, except for adequately treated carcinoma
of the cervix or basal or squamous cell carcinomas of the skin.
- Any process that compromises the ability to swallow and/or absorb oral medication.
- A history of any of the following autoimmune skin disorders: Sjogren's syndrome,
scleroderma, dermatomyositis, and systemic lupus erythematosus.
- Significant medical history or unstable medical conditions.
- Concurrent use of warfarin. Patients must be off warfarin for at least one week
prior to initiation of erlotinib. Other non-warfarin anticoagulants are permitted.
- Patients who require ongoing concomitant use of one of the strong inhibitors/inducers
- Pregnant or breastfeeding. Women of child-bearing potential must agree to use
adequate contraception prior to study entry and for the duration of study