pharmacokinetically-guided on the individualization of pembrolizumab administration in the treatment of lung cancer

Conditions: Non-small Cell Lung Cancer

Summary: pembrolizumab with or without chemotherapy has become the standard therapy in advanced non-small cell lung cancer (nsclc), with a fixed dose of 200mg every 3 weeks. the investigators performed this study to explore the clinical efficacy and safety of pharmacokinetic (pk)-guided pembrolizumab administration in advanced nsclc.

in this prospective, open-label, single-arm exploratory study, the investigators enrolled advanced nsclc patients without sensitizing egfr or alk mutation in sun yat-sen university cancer center. eligible patients received pembrolizumab 200mg every 3 weeks with or without chemotherapy for four cycles, then for patients without progressive disease, pembrolizumab was administrated in new dose-intervals according to steady state plasma-concentration (css) of pembrolizumab until disease progression. primary endpoint was the progression-free survival. patients with css of pembrolizumab also underthe investigatorsnt genetic polymorphism analysis of variable number of tandem repeats region (vntr) in neonatal fc receptor (fcrn).

Eligibility criteria:
inclusion criteria: 1. cytologically or histologically confirmed primary nsclc; 2. stage iv primary nsclc according to the international association for the study of lung cancer (iaslc) tnm eighth edition; 3. there must be at least one evaluable lesion judged according to recist1.1; 4. no sensitive mutation in egfr and negative alk rearrangement; 5. ≥18 years old; 6. the eastern cooperative oncology group (ecog) physical status score was 0-2; 7. life expectancy of more than 3 months; 8. bone marrow and organs (liver and kidney) function well, which can meet the conventional conditions for chemotherapy: neutrophil count ≥1.5×109/ l, platelet count ≥75×109/ l, hemoglobin ≥9g/ dl, total bilirubin ≤1.5×uln, transaminase ≤2.5×uln, serum creatinine ≤1.5×uln or creatinine clearance ≥45ml/min. (uln: upper limit of normal value); 9. for female subjects of reproductive age, urine or serum pregnancy test should be negative within 7 days prior to receiving the first study drug administration (cycle 1, day 1).if a urine pregnancy test is not confirmed negative, a blood pregnancy test is required;for men, consent must be given to use appropriate methods of contraception or surgical sterilization during the trial and for 8 weeks after the last administration of the experimental drug; 10. signing the informed consent; 11. good compliance, follow-up, and voluntary compliance with relevant regulations of the study.- exclusion criteria: 1. small cell lung cancer; 2. brain metastases with hemorrhage; 3. currently participating in interventional clinical research and treatment; 4. past anti-tumor immunotherapy with other anti-pd-1 /pd-l1 monoclonal antibodies; 5. have received solid organ or blood system transplantation; 6. an active autoimmune disease requiring systemic treatment (e.g., use of palliative drugs, corticosteroids, or immunosuppressants) occurred within 2 years prior to initial administration.alternative therapies (such as thyroxine, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency) are not considered systemic; 7. having been diagnosed with immunodeficiency or receiving systemic glucocorticoid therapy or any other form of immunosuppressive therapy within 7 days prior to the first administration of the study;physiological dose of glucocorticoids (≤10 mg/ day of prednisone or its equivalent) is allowed; 8. a history of non-infectious pneumonia requiring glucocorticoid therapy or current interstitial lung disease within 1 year prior to initial administration; 9. a known history of human immunodeficiency virus (hiv 1/2 antibody positive); 10. untreated active hepatitis b

Keywords: pembrolizumab pharmacokinetics non-small cell lung cancer