This phase II trial studies how well osimertinib, surgery, and radiation therapy work in treating patients with stage IIIB or IV non-small cell lung cancer with EGFR mutations. Osimertinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving osimertinib, surgery, and radiation therapy may work better at treating non-small cell lung cancer with EGFR mutations.
Name: Osimertinib
Name: Radiation Therapy
Name: Therapeutic Conventional Surgery
Description: Will be estimated using Kaplan-Meier method. The stratified log-rank test will be performed to test the difference in time-to-event distributions between treatment groups. Stratified Cox proportional hazards model will be utilized to include multiple covariates in the time-to-event analysis and to estimate hazard ratios.
Measure: Progression free survival (PFS) Time: From the start date of osimertinib assessed up to 4 yearsDescription: Will be estimated using Kaplan-Meier method. The stratified log-rank test will be performed to test the difference in time-to-event distributions between treatment groups. Stratified Cox proportional hazards model will be utilized to include multiple covariates in the time-to-event analysis and to estimate hazard ratios.
Measure: Overall survival Time: From the treatment start date assessed up to 4 yearsDescription: Will be estimated using Kaplan-Meier method. The stratified log-rank test will be performed to test the difference in time-to-event distributions between treatment groups. Stratified Cox proportional hazards model will be utilized to include multiple covariates in the time-to-event analysis and to estimate hazard ratios.
Measure: Time to progression of target lesions Time: Up to 4 yearsDescription: Will be estimated using Kaplan-Meier method. The stratified log-rank test will be performed to test the difference in time-to-event distributions between treatment groups. Stratified Cox proportional hazards model will be utilized to include multiple covariates in the time-to-event analysis and to estimate hazard ratios.
Measure: Time to appearance of new metastases Time: Up to 4 yearsDescription: Will be estimated using Kaplan-Meier method. The stratified log-rank test will be performed to test the difference in time-to-event distributions between treatment groups. Stratified Cox proportional hazards model will be utilized to include multiple covariates in the time-to-event analysis and to estimate hazard ratios.
Measure: PFS in oligometastatic subgroup Time: Up to 4 yearsDescription: Toxicity data related to the treatments will be summarized by frequency tables. The association between the types and severity of toxicity and the treatment groups will be evaluated.
Measure: Incidence of adverse events Time: Up to 30 days post treatmentAllocation: Randomized
Parallel Assignment
There are 3 SNPs
To determine whether osimertinib plus LCT improves progression-free survival compared with osimertinib alone in TKI naive EGFR (L8585R/exon 19 deletion) mutant metastatic NSCLC. --- L8585R ---
The association between the types and severity of toxicity and the treatment groups will be evaluated.. Inclusion Criteria: - Histologically or cytologically confirmed non-small cell lung cancer - Stage IIIB/IV or recurrent non-small cell lung cancer which is not amenable to curative intent therapy - Patients must have one of the following: - NSCLC which harbors EGFR exon 19 deletion or L858R mutation. --- L858R ---
In addition, these lesions will be counted towards the total number of metastases, and will also be counted as target lesions Inclusion Criteria: - Histologically or cytologically confirmed non-small cell lung cancer - Stage IIIB/IV or recurrent non-small cell lung cancer which is not amenable to curative intent therapy - Patients must have one of the following: - NSCLC which harbors EGFR exon 19 deletion or L858R mutation. --- L858R ---
This subset of patients must be TKI naive; OR - NSCLC which harbors an EGFR T790M mutation that was acquired following progression on erlotinib, gefitinib or afatinib. --- T790M ---
In addition, these lesions will be counted towards the total number of metastases, and will also be counted as target lesions EGFR Exon 19 Deletion Mutation EGFR NP_005219.2:p.L858R EGFR NP_005219.2:p.T790M Lung Non-Small Cell Carcinoma Recurrent Lung Non-Small Cell Carcinoma Stage IIIB Lung Cancer AJCC v8 Stage IV Lung Cancer AJCC v8 Stage IVA Lung Cancer AJCC v8 Stage IVB Lung Cancer AJCC v8 Carcinoma Lung Neoplasms Carcinoma, Non-Small-Cell Lung PRIMARY OBJECTIVES: I. To determine whether, in patients with tyrosine kinase inhibitor (TKI) naive or TKI resistant (acquired T790M) metastatic EGFR mutant non-small cell lung cancer (NSCLC) who do not progress after 6-12 weeks of induction osimertinib, local consolidative therapy (LCT; radiotherapy +/- surgical resection) followed by osimertinib prolongs progression-free survival (PFS) compared with osimertinib alone. --- T790M ---
To determine whether osimertinib plus LCT improves progression-free survival compared with osimertinib alone in TKI resistant (acquired T790M) EGFR mutant NSCLC. --- T790M ---