Local Consolidative Radiation Therapy Plus TKI Versus TKI Alone in Driver Mutated OM-NSCLC

Randomization Arms: Eligible patients will be randomized in 1:1 ratio to TKI alone or TKI + LCRT. This will be an intention to treat randomized study.

Arm 1: Continuation of TKI therapy alone Arm 2: Continuation of TKI therapy + Local Consolidative Radiation therapy to loc0-regional disease and 1-5 oligometastatic sites

Inclusion criteria

• Patients with pathologically proven diagnosis of NSCLC
• Patients with positive oncogene driver mutation (EGFR or ALK/ROS)
• Patients who have received at least 2-4 months of TKI therapy without progression
• Patients with 1-5 sites of metastatic disease not including the primary tumor and regional nodes (less than 3 metastatic lesions in one organ will be eligible and 4 or more metastatic lesions in one organ will be ineligible)
• Patients suitable for local consolidative therapy
• Adequate end-organ function CBC/differential obtained within 15 days prior to registration on study, with adequate bone marrow function defined as follows:

• Absolute neutrophil count (ANC) ≥ 500 cells/mm3;
• Platelets ≥ 50,000 cells/mm3;
• Hemoglobin ≥ 8.0 g/dl (Use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable);
• Patients with ECOG performance status of 0-2
• Age > 18 years
• For females of child-bearing potential, negative serum or urine pregnancy test within 14 days prior to study registration

Exclusion criteria

• Patients with progressive disease after 2-3 months of initial TKI therapy
• Patients with negative oncogene driver mutations (EGFR/ALK/ROS)
• Patients not suitable for local consolidative radiation therapy
• Patients who are not suitable for further continuation of TKI therapy due to toxicity
• Severe, active co-morbidity defined as follows:

• Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months;
• Transmural myocardial infarction within the last 6 months;
• Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration;
• Patients with prior history of radiation therapy to thorax
• Patients with second malignancy (Synchronous or Metachronous)
• Pregnancy