Cisplatin-Pemetrexed Compared With Carboplatin-Paclitaxel-Bevacizumab in KRAS Mutated Non-small Cell Lung Cancer

Inclusion Criteria:

1. Histologically or cytologically confirmed (non-squamous) NSCLC incurable locally advanced or metastatic (stage IIIB and stage IV) disease.
2. Documented KRAS mutation
3. Chemotherapy-naive NSCLC patients. Adjuvant chemotherapy or chemoradiotherapy is allowed when given \> 1 year for study entry. Previous anti-PD(L1) therapy for advanced disease is allowed.
4. At least one unidimensionally measurable lesion meeting RECIST1.1.
5. ECOG PS 0-2
6. Age ≥ 18 years
7. Adequate organ function, including:

   * Adequate bone marrow reserve: ANC ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L.
   * Hepatic: bilirubin ≤1.5 x ULN, AP, ALT, AST ≤ 3.0 x ULN AP, ALT, and AST ≤5 xULN is acceptable if the liver has tumor involvement
   * Renal: calculated creatinine clearance ≥ 60 ml/min based on the Cockroft-Gault formula.
   * Urine protein (dip-stick) \< 2 +; when ≥ 2 +: 24 hours urine protein ≤ 1 gr.
8. Signed informed consent
9. Male and female patients with reproductive potential must use an approved contraceptive method, if appropriate. Female patients with childbearing potential must have a negative serum pregnancy test within 7 days prior to study enrollment.

Exclusion Criteria:

1. Pregnant or lactating women
2. Clinically significant (i.e. active) cardiovascular disease: congestive heart failure \>NYHA class 2; CVA or myocardial infarction \< 6 months prior to study entry; uncontrolled hypertension (blood pressure systolic \> 150 mmHg and/or diastolic \> 100 mmHg)
3. History of hemoptysis ≥ grade 2 (bright red blood of at least 2,5 ml in the last 3 months)
4. Evidence of tumor invading major blood vessels on imaging (i.e. superior vena cava or pulmonary artery)
5. Patients with evidence or history of bleeding diathesis
6. Non-healing wound or ulcer