The recommended adjuvant therapy for stage Ⅱa-Ⅲb Non-small cell lung cancer (NSCLC) were perioperative chemotherapy. The adjuvant or neoadjuvant chemotherapy for early stage lung cancer improved about 5% 5-year survival. As for advanced NSCLC with epidermal growth factor receptor (EGFR) activating mutation, epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) combination with chemotherapy had improved progression-free survival (PFS) compared with EGFR-TKI alone. We propose this trial of Neoadjuvant Afatinib Combination With Chemotherapy for Stage Ⅱa-Ⅲb NSCLC With EGFR Activating Mutation, which would maximize benefit early in a patient's treatment course. At the same time, dynamic 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET) was used to evaluate the standardized uptake value (SUV) and uptake rate constant (Ki) changes of lesions before and after treatment, so as to accurately and quantitatively monitor the tumor response of different therapy.
The prognosis of stage Ⅱa-Ⅲb Non-small cell lung cancer (NSCLC) was worse, with 5-year survival rate between 26%-60%. The recommended adjuvant therapy for stage Ⅱa-Ⅲb NSCLC were adjuvant or neoadjuvant chemotherapy. As for advanced NSCLC with EGFR activating mutation, EGFR-TKI combination with chemotherapy had improved survival compared with EGFR-TKI alone. The Chinese Thoracic Oncology Group-1103 (CTONG-1103) trial showed that neoadjuvant erlotinib has better PFS than neoadjuvant chemotherapy. The investigators propose that neoadjuvant EGFR-TKI combination with chemotherapy for stage Ⅱa-Ⅲb NSCLC with EGFR activating mutation might have better pathological response and disease-free survival (DFS) than chemotherapy alone, and maximize benefit early in a patient's treatment course. At the same time, dynamic 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET) was used to evaluate the standardized uptake value (SUV) and uptake rate constant (Ki) changes of lesions before and after treatment, so as to accurately and quantitatively monitor the tumor response of different therapy.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
① Eligible patients with non-squamous cell lung cancer will receive pemetrexed 500mg/m2, IV on day 1 and cisplatin 75mg/m2 or carboplatin area under curve (AUC) =5, on day 1 of a 3-week schedule for 3 cycles. ② Eligible patients with squamous cell lung cancer will receive gemcitabine 1250mg/m2 IV on day 1 and day 8, and cisplatin 75mg/m2 or carboplatin AUC =5 on day 1 of a 3-week schedule for 3 cycles . ③Patient will take afatinib at dosage of 30mg per day 48 hours after chemotherapy and will stop 24 hours before next cycle of chemotherapy.
The patients who respond to neoadjuvant treatment (CR+PR) and the patients who do not respond to therapy but could still undergo surgery (SD and PD) will receive radical lung resection 3-4 weeks later after neoadjuvant.
The CR, PR and SD patients who have been treated surgically will take afatinib at a dosage of 30mg per day for 2 year.
Major pathological response
10% or less residual viable tumor cells
Time frame: up to 12 weeks; analysis of surgical resected tumor samples after neoadjuvant therapy
Objective response rate
Image assessment of tumor response according to RECIST 1.1 criteria
Time frame: up to 12 weeks; after neoadjuvant therapy
Progression free survival
Time from enrollment to disease progression or death from any cause, whichever occurred first
Time frame: Pts after surgery will receive long-term follow-up including chest CT scan, abdominal ultrasound every 3 months, brain MRI every 6 months, bone scan (ECT) every 12 months for up to 3 years
Overall survival
From date of randomization until the date of date of death from any cause, whichever came first, assessed up to 100 months
Time frame: up to 100 months
R0 resection
the proportion of patients with negative surgical margin and no residual found under microscope after resection in all patients who have completed the treatment
Time frame: up to 12 weeks; analysis of surgical resected tumor samples
Treatment related adverse events
the number of adverse events related to afatinib or platinum-based chemotherapy as evaluated according to CTCAE v4.0.
Time frame: 12 weeks
standardized uptake value (SUV) changes
standardized uptake value (SUV) changes before and after neoadjuvant therapy
Time frame: up to 12 weeks; before and after neoadjuvant therapy
uptake rate constant (Ki) changes
uptake rate constant (Ki) changes before and after neoadjuvant therapy
Time frame: up to 12 weeks; before and after neoadjuvant therapy
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