Summary

This trial studies the side effects of pembrolizumab with or without chemotherapy in treating patients with stage IV non-small cell lung cancer that has come back after a period of improvement (recurrent) and may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as pemetrexed and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving pembrolizumab with or without chemotherapy may shrink the tumor in older patients with non-small cell lung cancer.

Objectives

PRIMARY OBJECTIVE:
I. To estimate the adverse event profile of MK-3475 (pembrolizumab) over the first six months of treatment, in non-small cell lung cancer patients who are 70 years of age or older and who are treated with MK-3475 (pembrolizumab) +/- chemotherapy in a first-line setting.

SECONDARY OBJECTIVES:
I. To estimate overall survival.
II. To describe patient quality of life during the treatment using the Linear Analogue Self-Assessment (LASA) questionnaire.
III. To explore whether Comprehensive Geriatric Assessment (CGA) -derived risk score is able to predict rates of severe adverse events in older cancer patients who receive MK-3475 (pembrolizumab) or MK-3475 (pembrolizumab) + chemotherapy.

EXPLORATORY OBJECTIVES:
I. To disaggregate the adverse events and identify potential causes of individual adverse events.
II. To describe patient fatigue level as measured with the Multidimensional Fatigue Symptom Inventory – Short Form (MFSI-SF); exercise level using the Godin Leisure Time Exercise Questionnaire (GLTE); and other symptoms and concerns using the LASA questionnaires.
III. To estimate time-to-treatment failure for single-agent MK-3475 (pembrolizumab) and MK-3475 (pembrolizumab) + chemotherapy in older patients.

CORRELATIVE SCIENCE OBJECTIVES:
I. To evaluate whether older patients who experience fatigue or other adverse effects would be correlated with a change of PD-L1 therapy-responsive T cell subset (i.e. CX3CR1+CD11ahighCD8+ T-cells) in their peripheral blood from baseline (prior to therapy) to post therapy.
II. To determine the extent to which MK-3475 (pembrolizumab) demonstrates time dependent decrease in clearance in older adult patients (aged >= 70 years) with non-small cell lung cancer being treated with pembrolizumab monotherapy or in combination with cytotoxic chemotherapy.
III. To determine the intrapatient and interpatient variability in clearance in older adult (>= 70 years) patients with non-small cell lung cancer receiving pembrolizumab monotherapy and when combined with cytotoxic chemotherapy.
IV. To preliminarily explore the correlation between pembrolizumab exposure (AUC) with observed immune related toxicities in this older adult (aged >= 70 years) patient population receiving pembrolizumab monotherapy and when combined with cytotoxic chemotherapy.

OUTLINE: Patients are assigned to 1 of 2 groups.

GROUP A: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Cycles repeat every 21 or 42 days in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection throughout the study.

GROUP B: Patients receive pembrolizumab IV over 30 minutes on day 1. Cycles with pembrolizumab repeat every 21 or 42 days in the absence of disease progression or unacceptable toxicity. Patients also receive pemetrexed IV over 10 minutes, and carboplatin IV per institutional guidelines on day 1. Cycles with pemetrexed and carboplatin repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection throughout the study.

Patients undergo computed tomography (CT) scan, diagnostic imaging, and blood sample collection throughout the study.

After completion of study treatment, patients are followed up annually for up to 5 years after registration.