Clinical activity of programmed cell death 1 (PD-1) blockade in never, light, and heavy smokers with non-small-cell lung cancer and PD-L1 expression ≥50% Journal Article


Authors: Gainor, J. F.; Rizvi, H.; Jimenez Aguilar, E.; Skoulidis, F.; Yeap, B. Y.; Naidoo, J.; Khosrowjerdi, S.; Mooradian, M.; Lydon, C.; Illei, P.; Zhang, J.; Peterson, R.; Ricciuti, B.; Nishino, M.; Zhang, J.; Roth, J. A.; Grishman, J.; Anderson, D.; Little, B. P.; Carter, B. W.; Arbour, K.; Sauter, J. L.; Mino-Kenudson, M.; Heymach, J. V.; Digumarthy, S.; Shaw, A. T.; Awad, M. M.; Hellmann, M. D.
Article Title: Clinical activity of programmed cell death 1 (PD-1) blockade in never, light, and heavy smokers with non-small-cell lung cancer and PD-L1 expression ≥50%
Abstract: Background: Immune checkpoint inhibitors (ICIs) are standard therapies for patients with advanced non-small-cell lung cancer (NSCLC) and a programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) ≥50%. Tumor mutation burden (TMB) also predicts response to ICIs but is often not available in real time for decision making in the first-line setting. Smoking exposure can be a proxy for TMB in NSCLC. The impact of smoking status on efficacy of PD-1 blockade in NSCLC patients with PD-L1 TPS ≥50% has not been well defined. Patients and methods: To investigate the relationship between smoking and activity of ICIs in NSCLC, we retrospectively studied 315 patients with NSCLC and PD-L1 TPS ≥50% at five USA academic medical centers. Objective response rates (ORRs), progression-free survival (PFS), and duration of response (DOR) were compared between never (<100 lifetime cigarettes), light (≤10 pack-years), and heavy (>10 pack-years) smokers. A subset of patients underwent next-generation sequencing to estimate TMB. Results: We identified 36 (11%) never, 42 (13%) light, and 237 (75%) heavy smokers with NSCLC and PD-L1 TPS ≥50% treated with ICIs. Objective responses were observed in 27%, 40%, and 40% of never, light, and heavy smokers, respectively (P = 0.180 never versus heavy; P = 1.000 light versus heavy). Median PFS and median DOR were numerically shorter in never and light smokers compared with heavy smokers (PFS 3.0 versus 4.0 versus 5.4 months; median DOR 6.9 versus 10.8 versus 17.8 months), but were not statistically different [PFS: hazard ratio (HR) 1.37, P = 0.135 and HR 1.24, P = 0.272; DOR: HR 1.92, P = 0.217 and HR 1.79, P = 0.141]. Conclusions: PD-(L)1 inhibitors are associated with antitumor activity in NSCLC with PD-L1 TPS ≥50% regardless of smoking status. Nevertheless, there is a signal of potentially decreased durability among never and light smokers that should be further evaluated. Distinct immunobiologic features may affect initial response versus durability of antitumor immunity to programmed cell death 1 (PD-1) blockade. © 2019 The Authors
Keywords: adult; controlled study; protein expression; treatment response; aged; middle aged; major clinical study; drug efficacy; treatment duration; united states; protein function; ipilimumab; ticilimumab; progression free survival; cohort analysis; smoking; antineoplastic activity; retrospective study; scoring system; tumor immunity; sample size; programmed death 1 ligand 1; non small cell lung cancer; nsclc; high throughput sequencing; nivolumab; very elderly; human; male; female; priority journal; article; checkpoint kinase inhibitor; pembrolizumab; durvalumab; pd-l1 expression; pd-1 inhibitor; tumor mutation burden; tumor proportion score
Journal Title: Annals of Oncology
Volume: 31
Issue: 3
ISSN: 0923-7534
Publisher: Oxford University Press  
Date Published: 2020-03-01
Start Page: 404
End Page: 411
Language: English
DOI: 10.1016/j.annonc.2019.11.015
PUBMED: 32067682
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 2 March 2020 -- Source: Scopus
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MSK Authors
  1. Matthew David Hellmann
    256 Hellmann
  2. Kathryn Cecilia Arbour
    33 Arbour
  3. Hira Abbas Rizvi
    45 Rizvi
  4. Jennifer Lynn Sauter
    50 Sauter