Impact of smoking on efficacy of PD-1/PD-L1 inhibitors in non-small cell lung cancer patients: a meta-analysis

Li, Bingjia; Huang, Xiaoyu; Fu, Lei

doi:10.2147/ott.s156421

Cited by 51 publications

(43 citation statements)

References 23 publications

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“…Then, we drew a conclusion that regardless of smoking or not, patients in the experimental arms always benefit, which is consistent with the analysis of Lee et al [19]. It seemed that the conclusions drawn by Abdel-Rahman [17] and Li et al [18] could be reversed. Given the higher heterogeneity, we observed these 15 studies and hypothesized that differences in therapeutic regimens (anti-PD-1/PD-L1 monotherapy/ combined chemotherapy) of the experimental arms might be the underlying cause of heterogeneity.…”

Section: Discussionsupporting

confidence: 78%

“…Although previous meta-analyses have attempted to clarify the relationship between smoking and the efficacy of ICIs [17,18], due to the limitations of the number of studies, the types of carcinomas and lack of subgroup analysis, the results remained to be confirmed. In this meta-analysis, we included a large amount of high-quality trials without any restriction on carcinoma category.…”

Section: Discussionmentioning

confidence: 99%

“…Smoking is considered an adverse behavior and has been implicated in many clinical studies of anti-PD-1/ PD-L1 therapy as a part of patient characteristics. Previously, two pieces of meta-analyses have indicated that in NSCLC, smokers have a benefit tendency in anti-PD-1 therapy, while non-smokers may not [17,18]. However, another meta-analysis published in JAMA Oncology found the opposite [19].…”

Section: Introductionmentioning

confidence: 99%

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Smokers or non-smokers: who benefits more from immune checkpoint inhibitors in treatment of malignancies? An up-to-date meta-analysis

et al. 2020

World J Surg Onc

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Background: Immune checkpoint inhibitors, which are a milestone in anti-cancer therapy, have been applied in the treatment of multiple malignancies. Real-world data have suggested that smoking status may be associated with the efficacy of anti-PD-1/PD-L1 therapy. Hereby, to evaluate "smoking benefit or not", we included numerous high-quality randomized controlled clinical trials (RCTs) without any restriction on category. Methods: A systematic search of online database was performed from July 2010 to July 2019. Eligible studies included phase II/III RCTs comparing PD-1/PD-L1 inhibitors with chemotherapy in the treatment of multiple carcinomas and contained subgroup analysis of smoking status. Then, related hazard ratios (HRs) with 95% confidence intervals (CIs) of overall survival (OS) were pooled.Results: In the initial meta-analysis, compared with chemotherapy, the OS of non-smokers (HR, 0.81; 95% CI, 0.67-0.98) and smokers (HR, 0.77; 95% CI, 0.71-0.83) were significantly prolonged with PD-1/PD-L1 inhibitors. Outcomes from subgroup analysis showed that in anti-PD-1/PD-L1 monotherapy groups, non-smokers showed no significant improvement in OS (HR, 0.94; 95% CI, 0.83-1.06), while the OS of smokers was significantly prolonged (HR, 0.79; 95% CI, 0.74-0.85); in groups of PD-1/PD-L1 inhibitors combined with chemotherapy, the OS of non-smokers (HR, 0.45; 95% CI, 0.28-0.71) and smokers (HR, 0.72; 95% CI, 0.61-0.85) were significantly prolonged. Combined ipilimumab and chemotherapy showed no significance in both groups. Conclusion:Smokers benefit from either anti-PD-1/PD-L1 monotherapy or the combined regimen compared with chemotherapy. Considering cost-effectiveness, monotherapy was recommended to smokers. For non-smokers, only the combined regimen was feasible in non-small cell lung cancer.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Smokers or non-smokers: who benefits more from immune checkpoint inhibitors in treatment of malignancies? An up-to-date meta-analysis

et al. 2020

World J Surg Onc

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“…It is to be noted, that smoking status differentially modulates the response of patients to CPI treatment. In a phase III randomized control trial with 1981 NSCLC patients, PD-1 inhibitors worked more efficaciously in patients with a smoking history while nonsmoking patients showed no survival benefit [ 121 ]. A similar meta-analysis in NSCLC, urothelial cancer and HNSCC showed that smokers benefited from anti PD-1/PD-L1 mono or combination therapy while nonsmokers benefitted from a combination of chemo- and immunotherapy [ 122 ].…”

Section: Influence Of Lifestyle On Outcome Of Cpimentioning

confidence: 99%

The Confounders of Cancer Immunotherapy: Roles of Lifestyle, Metabolic Disorders and Sociological Factors

Deshpande

Sharma

Watabe

2020

Cancers

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Checkpoint blockade immunotherapy (CPI) is an effective treatment option for many types of cancers. Irrespective of its wide clinical implications, the overall efficacy remains unpredictable and even poor in certain pathologies such as breast cancer. Thus, it is imperative to understand the role of factors affecting its responsiveness. In this review, we provide an overview on the involvement of sociological factors, lifestyles and metabolic disorders in modulating the CPI response in patients from multiple malignancies. Lifestyle habits including exercise, and diet promoted therapeutic responsiveness while alcohol consumption mitigated the CPI effect by decreasing mutational burden and hampering antigen presentation by dendritic cells. Metabolic disorder such as obesity was recognized to enhance the PD-1 expression while diabetes and hypertension were consequences of CPI therapy rather than causes. Among the sociologic factors, sex and race positively influenced the CPI effectiveness on account of increased effector T cell activity and increased PD-1 expression while ageing impaired CPI responsiveness by decreasing functional T cell and increased toxicity. The combined effect of these factors was observed for obesity and gender, in which obese males had the most significant effect of CPI. Therefore these variables should be carefully considered before treating patients with CPI for optimal treatment outcome.

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“…Here, we retrospectively examined the relationship between smoking and efficacy of PD-(L)1 inhibitors among 315 patients with PD-L1 TPS ≥50%. Based upon retrospective studies in unselected patient populations, 9 , 14 we had originally hypothesized that never/light smokers would have limited clinical benefit from PD-(L)1 inhibition even in the setting of high PD-L1 expression. Instead, we observed fewer differences than initially anticipated.…”

Section: Discussionmentioning

confidence: 99%

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%

et al. 2020

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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.

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Impact of smoking on efficacy of PD-1/PD-L1 inhibitors in non-small cell lung cancer patients: a meta-analysis

Cited by 51 publications

References 23 publications

Smokers or non-smokers: who benefits more from immune checkpoint inhibitors in treatment of malignancies? An up-to-date meta-analysis

Smokers or non-smokers: who benefits more from immune checkpoint inhibitors in treatment of malignancies? An up-to-date meta-analysis

The Confounders of Cancer Immunotherapy: Roles of Lifestyle, Metabolic Disorders and Sociological Factors

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%

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