A Phase II randomized controlled trial of TKI Alone versus TKI and Local Consolidative Radiation Therapy in oncogene driver mutated oligo metastatic Non-small cell lung cancer patients.

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:

1. Patients with pathologically proven diagnosis of NSCLC

2. Patients with positive oncogene driver mutation (EGFR or ALK/ROS)

3. Patients who have received at least 2-4 months of TKI therapy without progression

4. 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)

5. Patients suitable for local consolidative therapy

6. 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);

7. Patients with ECOG performance status of 0-2

8. Age > 18 years

9. For females of child-bearing potential, negative serum or urine pregnancy test within 14 days prior to study registration

Exclusion Criteria:

1. Patients with progressive disease after 2-3 months of initial TKI therapy

2. Patients with negative oncogene driver mutations (EGFR/ALK/ROS)

3. Patients not suitable for local consolidative radiation therapy

4. Patients who are not suitable for further continuation of TKI therapy due to toxicity

5. 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;

6. Patients with prior history of radiation therapy to thorax

7. Patients with second malignancy (Synchronous or Metachronous)

8. Pregnancy

Protocol manuscript is published and the results will be published in International peer-reviewed journal