From Anti-PD-1/PD-L1 to CTLA-4 and to MUC1—Is the Better Response to Treatment in Smokers of Cancer Patients Drug Specific?

• Main Authors: Lishi Wang, Fengxia Liu, Jing Li, Li Ma, Helin Feng, Qingyi Liu, William C. Cho, Haiyong Chen, Hong Chen, Hua Guo, Zhujun Li, Scott C. Howard, Minghui Li, Baoen Shan, Weikuan Gu, Jiafu Ji
• Format: Article
• Language: English
• Published: MDPI AG 2021-09-01
• Series: Journal of Personalized Medicine
• Subjects: cancer; clinical predictor; drug; hazard ratio; lung; smoking
• Online Access: https://www.mdpi.com/2075-4426/11/9/914

Whether smokers respond to anti-cancer drugs differently than non-smokers remains controversial. The objective of this study is to explore whether the better response of the smokers is specific to therapy of anti-PD-1/PD-L1, anti-checkpoint inhibitor, individual drugs on the cell surface, or lung cancer. Our results showed that among all non-small cell lung cancer (NSCLC) patients, when the data from anti-PD-1/PD-L1, anti-CTLA-4, and anti-MUC1 drugs are combined, the mean hazard ratios (HR) of smokers and non-smokers were 0.751 and 1.016, respectively. A meta-analysis with a fixed effect (FE) model indicated that the smokers have an HR value of 0.023 lower than that of the non-smokers. A stratified subgroup meta-analysis indicated that when treated with anti-CTLA-4 drugs, smokers had reduced HR values of 0.152 and 0.165 on average and FE model meta-analysis, respectively. When treated with an anti-MUC1 drug, smokers had reduced HR values of 1.563 and 0.645, on average and FE model meta-analysis, respectively. When treated with a combination of nivolumab and ipilimumab drugs, smokers had, on average, reduced HR and FE model meta-analysis values (0.257 and 0.141), respectively. Smoking is a clinical response predictor for anti-PD/PD-L1 monotherapy or first-line treatment in lung, urothelial carcinoma, and head and neck cancer. Smokers treated with other drugs have shown worse responses in comparison to non-smokers. These data suggest that, along with the progress in the development of new drugs for cancer, drugs acting on specific genotypes of smokers likely will arise.