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?

Abstract

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.

Cell adhesion molecules and immunotherapy in advanced non-small cell lung cancer: Current process and potential application

“…A study showed that high level of circulating monocytic myeloid-derived suppressive-like cells was related to primary resistance to immunotherapy (192). Interestingly, smoking patients with NSCLC seemed to have better responses to anti-PD-1/PD-L1, anti-CTLA-4, and anti-MUC1 drugs compared with non-smokers, which might affect therapy selection for smokers with NSCLC (193). The mechanisms of primary or secondary ICI resistance in NSCLC during anti-PD-1/PD-L1 therapy.…”

Bring the life stages into the domain of basic and clinical pharmacology

“…As different life stages have different physiological and pathological statuses, the same therapeutic treatment on different life stages has a different effect ( Wang et al, 2017 ; Wang et al, 2021 ). A typical example is hormone replacement therapy ( Lobo, 2017 ).…”