This research study is studying a combination of two drugs as a possible treatment for Non-Small Cell Lung Cancer (NSCLC) with an EGFR mutation. The interventions involved in this study are: - Osimertinib (Tagrisso) - Gefitinib (Iressa)
Name: Gefitinib
Description: gefitinib is a EGFR inhibitorType: DrugGefitinib + Osimertinib
Name: Osimertinib
Description: An orally available, irreversible, third-generation, mutant-selective epidermal growth factor receptor (EGFR) inhibitorType: DrugGefitinib + Osimertinib
Description: The feasibility of combination gefitinib/osimertinib dosing will be determined through evaluation of the number of patients in each cohort who are able to remain on combination therapy for 6 x 28 day cycles.
Measure: Number of patients completing combination therapy with gefitinib and osimertinib for 6 x 28 day cycles Time: 3 yearsDescription: CTCAE v4.0 will be used to monitor toxicities in patients on combination therapy with gefitinib and osimertinib.
Measure: Rate of treatment-related Grade 3-5 adverse events Time: 3 yearsDescription: RECIST 1.1 measurements of CT scans of the chest/abdomen/pelvis will be measured every 2 cycles on treatment to determine the objective response rate for patients being treated with combination gefitinib and osimertinib.
Measure: Objective response rate Time: 3 years (each cycle is 28 days)Description: The Kaplan-Meier method will be used to determine the progression-free survival of patients enrolled on protocol and treated with combination gefitinib and osimertinib.
Measure: Progression free survival Time: 3 yearsDescription: Survival follow-up with clinic visits or phone calls will be used to monitor for overall survival from time of study randomization to death from any cause. The Kaplan-Meier method will be used to calculate overall survival.
Measure: Overall Survival Time: 3 yearsSingle Group Assignment
There are 2 SNPs
The Kaplan-Meier method will be used to calculate overall survival.. Inclusion Criteria: - Participants must have histologically confirmed stage IV NSCLC (per AJCC 7th edition) from time of diagnosis with either the L858R or exon 19 deletion activating EGFR mutation as identified in a CLIA-approved laboratory. --- L858R ---
Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with gefitinib or osimertinib, breastfeeding should be discontinued if the mother is treated with these agents Inclusion Criteria: - Participants must have histologically confirmed stage IV NSCLC (per AJCC 7th edition) from time of diagnosis with either the L858R or exon 19 deletion activating EGFR mutation as identified in a CLIA-approved laboratory. --- L858R ---
Patients must be off warfarin for >7 days prior to enrollment - Identification of EGFR T790M in baseline cfDNA analysis - Active pregnancy or breast-feeding. --- T790M ---
However, even though these drugs can be very effective, after a period of time, most EGFR tumors will develop resistance to this treatment, most often because of a second mutation in EGFR called T790M. --- T790M ---
Osimertinib is currently approved only to treat patients whose cancers develop resistance to gefitinib (or other similar EGFR inhibitors) because of the T790M mutation. --- T790M ---