Section to complete information about primary and secondary outcomes including. It includes the metric or method of measurement used and, the time point for every outcome.
Primary outcome(s):
1- Activation of EGFR, cell proliferation, apoptosis and angiogenesis (in tumor biopsy measured by multiparametric immunofluorescence staining techniques). Measurement time: At baseline, 6 months and 24 months.
2- Cellular inflammatory infiltrate (measurement of CD3, CD8, Treg and B lymphocytes, myeloid suppressor cells (MDSC and/or DC), macrophages (M1/M2), as well as PD expression measured by multiparametric immunofluorescence staining techniques). Measurement time: At baseline, 6 months and, 24 months
3- EGFR, KRAS mutations and EGF gene polymorphism (measurement by liquid biopsy). Measurement time: At baseline
4- Cytokines and EGFR growth factors (concentrations of EGF, TGF alpha, IL-6, IL8, CCL20, CXCL5, CCL2, CCL4, CCL5, CXCL9, CXCL10 through Luminex technology using ELISAS kit. In the case of EGF in serum will be measured through a commercial ELISA system). Measurement time: 6 and 24 months.
5- Genetic characteristics of the bronchial epithelium (will be evaluated by nasal brushing). Measurement time: At baseline, 6 months and 24 months
6- EGF concentration and antibody response vs EGF. (Ab vs EGF concentrations by means of an ELISA assay). Measurement time: At baseline, 6 months and 24 months
7- Lymphocyte subpopulations in circulating peripheral mononuclear cells (PBMC): (quantification of naïve CD8 T cells, effector CD8 T cells, naïve CD4 T cells, effector T CD4, Th17 cells, T regs cells, CD19+ B cells, CD4+ T cells, CD8+ T, CD8+ CD28- T cells, CD4/CD8 ratio, other cells will be purified with Ficoll-Paque PLUS reagent (AmershamBiosciences), by density gradient after centrifugation). Measurement time: At baseline, 6 months and 24 months
8- Overall survival (the time from the date of inclusion in the study until the date of death. If there is no certainty of the patient's death, the time elapsed until the date on which the latest news about the patient is recorded in the clinical history will be recorded). Measurement time: 24 months
9- Progression-Free survival (Time from the date of inclusion in the study until the date of disease progression, or death from any cause). Measurement time: every 3 months during 24 months
Key secondary outcomes:
1. Objective response (Performed using RECIST criteria and classified as Complete response, Partial response, Stable disease or Disease progression). Measurement time: At baseline and, every 3 months during 24 months
2. Adverse Events- AE (It will be measured taking into account Type of AE (Dermatological system disease, Gastrointestinal system disease, Respiratory system disease, general, and others), Duration of the AE (time from start AE until finish AE), AE intensity (Grade 1 or mild, Grade 2 or moderate. Grade 3 or severe, Grade 4 or Adverse event with risk of mortality or disability and Grade 5 or Death associated with an adverse event), Causal relationship (causation definite, very likely, probable, possible, unrelated, unknown), Severity (not serious/not serious, requires hospitalization, prolongs hospitalization, results in disability, life-threatening, causes death), Attitude toward treatment (no change , dose modification, temporary interruption, permanent interruption), AE outcome (recovered without sequelae, sequelae not requiring treatment, sequelae requiring treatment, death)). Measurement time: From the beginning of treatment until 24 months
