title: Clinical Determinants of Durable Clinical Benefit of Pembrolizumab in Veterans With Advanced Non-Small-Cell Lung Cancer.
abstract: Because of the prevalence of smoking in the veteran population, non-small-cell lung cancer (NSCLC) remains a significant cause of morbidity and mortality. The objectives of our study were to evaluate the extent of durable clinical benefit (DCB) to pembrolizumab in veterans with metastatic NSCLC and to identify clinical determinants of DCB.
  
  
  
  Prospective clinical data on veterans receiving pembrolizumab were collected. Duration of response was calculated from the first date of infusion until date of disease progression on computed tomography scans, defined according to Response Evaluation Criteria in Solid Tumors version 1.1 (CTCAE).
  
  
  
  As of the censor date, 25 veterans consented and 24 were evaluable. The response rate was 25% (6 of 24 patients), with all achieving a partial response. Four patients received palliative radiation because of focal progression and continued to receive pembrolizumab, leading to a DCB rate of 41% (10 of 24 patients). The mean duration of response at the censor date was 12.9 months (95% confidence interval [CI], 9.9-15.9) and 2.7 months (95% CI, 1.9-4.3) for those with and without DCB, respectively. Patients without DCB had a higher pack-year smoking history (P = .007). An increase in peripheral blood absolute lymphocyte count (ALC) during therapy was seen in patients with DCB (P = .073). There were no CTCAE Grade > 3 adverse events. All immune-related adverse events occurred in patients with DCB.
  
  
  
  Nearly half of the veterans exhibited DCB and pembrolizumab therapy was well tolerated. An increase in ALC from baseline and occurrence of autoimmune phenomena might be associated with DCB. Immunotherapy with pembrolizumab is a promising therapeutic strategy in veterans with advanced NSCLC.
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, University of Michigan Hospital, Ann Arbor, MI. Electronic address: qina@med.umich.edu.
authors.forename: Angel
authors.initials: A
authors.lastname: Qin
authors.affiliation: VA Ann Arbor Healthcare System, Ann Arbor, MI.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Street
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, University of Michigan Hospital, Ann Arbor, MI; VA Ann Arbor Healthcare System, Ann Arbor, MI.
authors.forename: Kemp
authors.initials: K
authors.lastname: Cease
authors.affiliation: VA Ann Arbor Healthcare System, Ann Arbor, MI; Department of Radiology, University of Michigan Hospital, Ann Arbor, MI.
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Viglianti
authors.affiliation: Clinical Research Division, Program in Immunology, Fred Hutchinson Cancer Research Center, Seattle, WA; Division of Medical Oncology, Department of Medicine, University of Washington Medical Center, Seattle, WA.
authors.forename: Edus H
authors.initials: EH
authors.lastname: Warren
authors.affiliation: Department of Biostatistics, University of Michigan, Ann Arbor, MI.
authors.forename: Lili
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, University of Michigan Hospital, Ann Arbor, MI; VA Ann Arbor Healthcare System, Ann Arbor, MI.
authors.forename: Nithya
authors.initials: N
authors.lastname: Ramnath
mesh_terms: D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000074322:Antineoplastic Agents, Immunological / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy*; D015897:Comorbidity; D018450:Disease Progression; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D066066:Response Evaluation Criteria in Solid Tumors; D012907:Smoking; D014057:Tomography, X-Ray Computed; D014728:Veterans
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000074322:Antineoplastic Agents, Immunological; C582435:pembrolizumab
keywords: Checkpoint inhibitors; Immunotherapy; Lymphocyte count; NSCLC; Response rate